A consecutive case series of defects reconstructed using NovoSorbⓇ Biodegradable Temporising Matrix: Initial experience and early results

BackgroundNovoSorb^Ⓡ Biodegradable Temporising Matrix (BTM) is a synthetic dermal template recently approved for treatment of full thickness defects of the skin. It requires a two-stage reconstruction where it is initially placed into a defect to generate a neodermis, which is later covered by a split skin graft. It has previously been described for the treatment of acute full thickness burn injury, necrotising fasciitis and free flap donor site reconstruction.MethodsA consecutive case series review of patients treated with BTM at Middlemore Hospital was performed. Patient demographics, defect aetiology, indications for dermal matrix use, surgical details, and complications were recorded using information gathered from the medical records.ResultsThis case series included 25 patients with a range of defects resulting from acute full thickness burn injury, burn scar revision, necrotising soft-tissue infection, tumour excision and traumatic loss. In these patients, 72% of wounds were identified as complex defects with exposed bone or tendon. Complications encountered included infection, non-adherence and incomplete vascularisation.ConclusionBTM provided a good reconstructive option for a wide range of defects, many of which were not amenable to immediate skin grafting. Once vascularised and ready for the second stage, it developed a red-pink colour and demonstrated capillary refill. Similar to other dermal matrices, infection was a commonly encountered problem. However, BTM proved more tolerant to this and was able to be salvaged in most cases, allowing the second stage to proceed as normal.     

Management of severe hand wounds with Integra® dermal regeneration template

We report our experience with the use of Integra? for the management of severe traumatic wounds of the hand. Fifteen patients were treated with follow-up ranging from 10 to 37 months. Wounds were associated with an osseous and/or joint and/or tendon exposure. Following Integra? placement, patients were managed with dressings and subsequent split-thickness skin grafting an average of 26 days later. Integra? was successful in achieving durable, functional and aesthetic definitive coverage in 13 of 15 applications while allowing a satisfying pollicidigital prehension. Regarding our clinical experience, Integra? is an effective technique to deal with severe wounds of the hand with exposed tendon and/or bone and/or joint, even in the absence of paratenon or periosteum. This can potentially lessen the need for local rotational or free flap coverage and should be taken into consideration as a viable alternative in traumatic reconstruction of the hand.     

A preliminary investigation of the reinnervation and return of sensory function in burn patients treated with INTEGRA®

Background

Loss of sensory function in scar after burn is common, although the basis for this loss is not clear. Additionally, little is known about the effects of different treatment modalities on sensory function and neuroanatomical outcomes in burn patients. Here, we investigated the effects of the use of the INTEGRA^® dermal scaffold on neuroanatomy and sensory function in acute burn patients.

Hypothesis and objectives

We hypothesized that the use of artificial dermal templates would inhibit or reduce reinnervation after excision, since regrowth of nerves requires complex molecular interactions. Therefore the primary objective of this study was to identify whether there is regrowth of nerve fibres in the INTEGRA^® dermal scaffold. The secondary objective was to identify whether the INTEGRA^® dermal scaffold reduced nerve regrowth or limited sensory function outcomes in acute burn patients.

Methods

Five patients treated with INTEGRA^®, cultured epithelial autograft spray (prepared using ReCell^® (CEA)) and split skin graft (SSG) were assessed for sensory function in scar and uninjured contralateral control skin. Neuroanatomy of scar and control sites was assessed using immunohistochemistry for PGP9.5, CGRP and substance P neuronal markers. Nerve density and sensory function was also assessed in a comparative group (n = 8) treated with CEA and SSG only.

Results

Neuroanatomy was not significantly different in the INTEGRA^® patients when compared to the CEA/SSG group only. The patients treated with INTEGRA^® had worse sensory function than those with CEA/SSG only.

Conclusions

Peripheral nerves do reinnervate the INTEGRA^® dermal scaffold. There is no statistically significant reduction in reinnervation observed when compared to a control group. It is possible that the use of artificial dermal constructs, while permissive for nerve regrowth, limit functionality when compared to nerves that regrow through dermal tissue. Further research to understand the causes of this, and into enhancing reinnervation in dermal scaffolds may improve sensory outcome in the most severely burned patients.     

A multicenter prospective trial evaluating fetal bovine dermal graft (Xenform® Matrix) for pelvic reconstructive surgery

Background

Most bladder tumors are derived from the urothelium. Benign mesenchymal tumors are rare. Leiomyoma of the bladder is the most common benign neoplasm. We present a case of leiomyoma of the bladder presenting with acute urinary retention in a female patient and report on the post-operative change in urodynamic findings. To our knowledge, few cases of this kind have been reported.

Case Presentation

A 56-year-old woman presented with acute urinary retention. Evaluations including ultrasound, magnetic resonance imaging, cystoscopy, and urodynamics contributed to a diagnosis of leiomyoma of the bladder. Various medications were ineffective for solving her lower urinary tract symptoms; therefore, a transurethral resection was performed. The final pathological report was leiomyoma. After the operation, her symptoms resolved; this improvement was confirmed by an urodynamic analysis. The postoperative urodynamics demonstrated a lower frequency of detrusor overactivity during filling cystometry and an increase in the uroflow rate, with reduced detrusor pressure in a pressure flow study.

Conclusions

Leiomyoma of the bladder can cause female outlet obstruction. A review of the literature and disease management is discussed.     

The LMA® ProtectorTM in anaesthetised,non-paralysed patients: a multicentre prospective observational study

We evaluated the LMA ^® Protector^TM in 280 ASA physical status 1–3 patients aged 18–75 years by assessing the ease of insertion, insertion time, oropharyngeal leak pressure, ease of gastric tube passage and complications. First-attempt and overall insertion success was 234/280 (84; 95%CI 79–88%) and 274/280 (98; 95–99%). Median (IQR [range]) insertion time was 17 (12–25 [5–44]) s, and manoeuvres to facilitate insertion were required in 56 (50–63)% of patients. Median oropharyngeal leak pressure was 31 (26–36 [14–40]) cmH₂O. Multivariate analysis identified two risk factors for oropharyngeal leak pressure < 25 cmH₂O: male sex (OR 2.44; 1.01–5.91, p = 0.048) and the insertion of a LMA size different to that recommended by weight (OR 1.98; 0.97–4.03, p = 0.06). Gastric tube insertion was possible in 256 out of 274 patients (93%). On fibreoptic view, vocal cords were visible in 86% of patients. During maintenance, 14 patients (5%) required airway manipulation. There were no episodes of regurgitation or aspiration. Blood staining on LMA removal was present in 70 out of 280 patients (25%). Use of the LMA Protector appears safe and is associated with a high success rate, provision of a highly effective seal and low rates of clinical complications. These attributes would suggest considerable potential for use during anaesthesia.     

β-Glucan treatment prevents progressive burn ischaemia in the zone of stasis and improves burn healing: An experimental study in rats

Saving the zone of stasis is one of the major goals of burn specialists. Increasing the tissue tolerance to ischaemia and inhibiting inflammation have been proposed to enable salvage of this zone. After a burn, excessive inflammation, including increased vascular permeability, local tissue oedema and neutrophil activation, causes local tissue damage by triggering vascular thrombosis and blocking capillaries, resulting in tissue ischaemia and necrosis. Oxygen radicals also contribute to tissue damage after a burn. However, macrophages play a pivotal role in the response to burn. We studied β-glucan because of its many positive systemic effects that are beneficial to burn healing, including immunomodulatory effects, antioxidant effects (free-radical scavenging activity) and effects associated with the reduction of the inflammatory response.     

Topical negative pressure therapy: Does it accelerate neovascularisation within the dermal regeneration template,Integra? A prospective histological in vivo study

Background

The use of topical negative pressure (TNP) dressings with dermal regeneration template (DRT), Integra, has improved outcomes and simplified aftercare. Previous clinical studies have suggested accelerated vascularisation; with a reduction in the duration of the 1st stage after the application of Integra, from 2 to 4 weeks to as little as 4 days, but with no histological evidence. However, histological studies, without TNP, have shown that vascularisation occurs between the second and the fourth week. This study set out to examine histologically the rate of DRT neovascularisation when combined with TNP.

Methods

Eight patients with nine reconstruction sites were enlisted. Unmeshed Integra and fibrin sealant to promote adherence were used. TNP was applied for the duration between the 1st and the 2nd stages. Patients underwent serial biopsies on days 7, 14, 21 and 28 post-application. The biopsies were stained with H&E and endothelial markers CD31 and CD34. Template vascularisation was assessed as a percentage of the template depth in which patent, canalised vascular channels could be demonstrated.

Results

The median percentage of the template depth which demonstrated canalised channels was 0%, 20%, 61% and 80% for days, 7, 14, 21 and 28, respectively.

Conclusion

The application of TNP dressings to dermal templates can reduce shearing forces, restrict seroma and haematoma formation, simplify wound care and improve patient tolerance. However, this study could not demonstrate that TNP accelerates neovascularisation as verified by the presence of histologically patent vascular channels.     

Role of Wnt/β-catenin and RANKL/OPG in bone healing of diabetic Charcot arthropathy patients: A prospective study in 24 patients followed for 2 years

Background and purpose

Charcot neuropathy is characterized by bone destruction in a foot leading to deformity, instability, and risk of amputation. Little is known about the pathogenic mechanisms. We hypothesized that the bone-regulating Wnt/β-catenin and RANKL/OPG pathways have a role in Charcot arthropathy.

Patients and methods

24 consecutive Charcot patients were treated by off-loading, and monitored for 2 years by repeated foot radiography, MRI, and circulating levels of sclerostin, dickkopf-1, Wnt inhibitory factor-1, Wnt ligand-1, OPG, and RANKL. 20 neuropathic diabetic controls and 20 healthy controls served as the reference.

Results

Levels of sclerostin, Dkk-1 and Wnt-1, but not of Wif-1, were significantly lower in Charcot patients than in the diabetic controls at inclusion. Dkk-1 and Wnt-1 levels responded to off-loading by increasing. Sclerostin levels were significantly higher in the diabetic controls than in the other groups whereas Wif-1 levels were significantly higher in the healthy controls than in the other groups. OPG and RANKL levels were significantly higher in the Charcot patients than in the other groups at inclusion, but decreased to the levels in healthy controls at 2 years. OPG/RANKL ratio was balanced in all groups at inclusion, and it remained balanced in Charcot patients on repeated measurement throughout the study.

Interpretation

High plasma RANKL and OPG levels at diagnosis of Charcot suggest that there is high bone remodeling activity before gradually normalizing after off-loading treatment. The consistently balanced OPG/RANKL ratio in Charcot patients suggests that there is low-key net bone building activity by this pathway following diagnosis and treatment. Inter-group differences at diagnosis and changes in Wnt signaling following off-loading treatment were sufficiently large to be reflected by systemic levels, indicating that this pathway has a role in bone remodeling and bone repair activity in Charcot patients. This is of particular clinical relevance considering the recent emergence of promising drugs that target this system.Charcot neuropathy mainly affects diabetic patients with bilateral peripheral neuropathy and is characterized by degenerative changes of the bone, joints, and soft tissues of the foot and ankle. However, the pathophysiological processes that lead to acute Charcot foot remain obscure. The identification of a cytokine system belonging to the tumor necrosis factor family—consisting of RANKL (receptor activator of nuclear factor-κB ligand), its receptor RANK (receptor activator of nuclear factor-κB), and its soluble decoy receptor, osteoprotegerin (OPG)—has substantially increased our understanding of bone regulatory mechanisms responsible for osteolytic activity by osteoclasts. The RANKL/OPG pathway has therefore been implicated in an increasing number of diseases affecting the bone, and several review articles have hypothesized about the possible role of this pathway in Charcot arthropathy (Jeffcoate 2008, Mascarenhas and Jude 2013), although only a few studies have been published. Although there has been much interest in RANKL/OPG signaling, recent research has significantly increased our understanding of the pivotal role played by other pathways in bone regulation. One such pathway is that of Wnt, which has been shown to be a key regulator of embryonic bone development, mechanical loading and unloading of the skeleton, bone growth, bone remodeling, and fracture repair by increasing osteoblast commitment from progenitor cells and by stimulating their proliferation and activation (Agholme and Aspenberg 2011, Kim et al. 2013). In addition, there is crosstalk between the bone anabolic Wnt pathway and the bone-catabolic RANKL/OPG pathway (Diarra et al. 2007), with recent studies suggesting that the Wnt pathway is in control of osteoclast differentiation and activation through its actions on the osteoblasts, and by participating in osteoclast recruitment and the initiation of bone remodeling (Bellido 2014). We are not aware of any study investigating the role of the Wnt system in the pathology of Charcot arthropathy.In this 2-year longitudinal, observational study in Charcot patients, we repeatedly measured plasma levels of endogenous mediators forming part of the RANKL/OPG and Wnt/ß-catenin pathways with the aim of elucidating their role in the pathophysiology of Charcot arthropathy from the acute phase until reaching a cold/chronic state.     

Clinical characteristics and treatment of burn wound sepsis in extensive burn patients: successful experience with eight cases

Eight burn wound sepsis patients, in which 6 cases were diagnosed as MODS and two as septic shock, were treated consecutively in our hospital from September 1997 to October 1998. The plasma concentration of IL-6, IL-8, TNFα and LPS were assayed before and after surgical intervention, as well as when the patients' vital signs became stable. The results showed: ①The patients' conditions abruptly deteriorated when the burn wound sepsis emerged;②The major cause related to burn wound sepsis was extensive burn injuries, with large areas of deep burn remaining open; ③Although wound swabs taken on admission revealed the presence of colonization by many pathogenic bacteria, Pseudomonas aeruginosa was one of the most frequent bacteria isolated from the subeschar tissue; ④The plasma concentrations of IL-6, IL-8, TNF and LPS before surgical intervention were significantly higher than that after surgical intervention (P＜0.05) ;⑤The lowest level of the inflammatory mediators was observed when the patients' conditions became stable, as compared with before surgical intervention (P＜0. 001).These findings suggest that the clinical characteristics of burn wound sepsis are abrupt deterioration of the general condition and prominent septic symptoms, often complicated by MODS. The main cause of burn wound sepsis is the presence of a large area of open deep burn wounds, which should be excised and covered early. LPS and pro-inflammatory mediators play an important role in the pathogenesis of burn wound sepsis. Although success in treating these patients is the result of appropriate application of multiple treatments, early, aggressive and thorough surgical excision of invasive burn infectious tissue and closure of wound play a crucial role in the successful treatment of patients complicated by burn wound sepsis. Other treatments are adjuvant but also important.     

Knee arthroplasty: are patients' expectations fulfilled?: A prospective study of pain and function in 102 patients with 5-year follow-up

Background and purpose With an aging population expecting an active life after retirement, patients’ expectations of improvement after surgery are also increasing. We analyzed the relationship between preoperative expectations and postoperative satisfaction and self-reported outcomes with regard to pain and physical function after knee arthroplasty.Patients and methods 102 patients (39 men) with knee osteoarthritis and who were assigned for TKR (mean age 71 (51–86) years) were investigated with KOOS, SF-36, and additional questions concerning physical activity level, expectations, satisfaction, and relevance of the outcome to the patient. These investigations took place preoperatively and postoperatively after 6 months, 1 year, and 5 years of follow-up.Results Response rate at 5 years was 86%. In general, the patients’ preoperative expectations were higher than their postoperative ability. For example, 41% expected to be able to perform activities such as golfing and dancing while only 14% were capable of these activities at 5 years. Having high or low preoperative expectations with regard to walking ability or leisure-time activities had no influence on the KOOS scores postoperatively. 93% of the patients were generally satisfied 5 years postoperatively, while 87% were satisfied with the relief of pain and 80% with their improvement in physical function at that time.Interpretation With an expanding population of mentally alert elderly, we can expect that great demands will be put on joint replacements. This study shows that patients have high preoperative expectations concerning reduction of pain. To a considerable extent, these expectations are fulfilled after one year. Expectations concerning demanding physical activities are not fulfilled to the same degree; however, most patients reported general satisfaction with the outcome indicating that satisfaction is not equivalent to fulfilled expectations. Preoperative counseling should include realistic information on outcomes concerning physical function and pain relief.     

Analysis of surgery-related complications in thyroid carcinoma — A German prospective multicentre study with 275 patients

Summary   Background: The rate of postoperative complications following surgery for thyroid carcinoma is increased compared to that following benign goitre surgery; however, risk factors have not been investigated systematically. Methods: A prospective multicentre study was conducted from 1 January to 31 December 1998. During that period 275 patients were treated for thyroid carcinoma in 45 hospitals including 5 university hospitals. Results: By univariate analysis no difference in complication rates could be shown for primary surgery versus redo surgery (completion surgery or surgery for recurrent carcinoma). Additionally, tumour size (pT4) was a significant risk factor for prolonged postoperative ventilation, general complications and permanent hypoparathyroidism. Lymphadenectomy evolved as a major risk factor for permanent hypoparathyroidism. By multivariate analysis independent risk factors were evaluated for 1) tracheotomy: tumour size (pT4 versus pT1–3), relative risk (RR) 2.1; 2) permanent recurrent laryngeal nerve (RLN) palsy: lymphadenectomy in the left cervicolateral compartment (C3), RR 5.4, and resection of soft tissue (muscle), RR 4.4; 3) transient hypocalcaemia: tumour size (pT4 versus pT1–3), RR 1.25, and extent of resection (subtotal resection versus total thyroidectomy), RR 3.02; 4) permanent hypoparathyroidism: lymphadenectomy, RR 8.01, and resection of soft tissue (vessels), RR 5.70. Conclusions: The results of the risk analysis might help to identify patients at increased risk for postoperative complications who should receive treatment in specialised hospitals.      

Clinical outcomes in ‘diabese’ burn patients: A systematic review and meta-analysis

ObjectiveThe objective of this study was to update the current status of clinical outcomes in diabetic (type II) and obese (BMI: 30–39.9 kg/m²) burn patients.MethodsWe adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched MEDLINE (PubMed), Google Scholar, Scopus, and Embase for studies related to a number of comorbidities and burn outcomes. Search terms for each of these databases are listed in the Appendix. From this search, we screened 6923 articles. Through our selection criteria, 12 articles focusing on either diabetes or obesity were selected for systematic review and meta-analysis. Data was analyzed using the “meta” package in R software to produce pooled odds ratios from the random effect model.ResultsDiabetic patients had 2.38 times higher odds of mortality [OR: 2.38, 95% CI:1.66, 3.41], however no statistically significant difference was found in mortality in obese patients [OR: 2.49, 95% CI: 0.36, 17.19]. Obese patients had 2.18 times higher odds of inhalation injury [95%CI: 1.23, 3.88], whereas diabetic patients did not show a difference in odds of inhalation injury [OR:1.02, 95% CI: 0.57, 1.81]. Diabetic patients had higher odds of complications resulting from infection: 5.47 times higher odds of wound, skin, or soft tissue infections [95% CI:1.97, 15.18]; 2.28 times higher odds of UTI or CAUTI [95% CI:1.50, 3.46]; and 1.78 times higher odds of pneumonia or respiratory tract infections [95% CI:1.15, 2.77]. Obese patients also had similar complications related to infection: 2.15 times higher odds of wound infection [95% CI: 1.04, 4.42] and 1.96 times higher odds of pneumonia [95% CI: 1.08, 3.56]. Other notable complications in diabetic patients were higher odds of amputation [OR: 37, 95% CI: 1.76, 779.34], respiratory failure [OR: 4.39, 95% CI: 1.85, 10.42], heart failure [OR: 6.22, 95% CI: 1.93, 20.06], and renal failure [OR: 2.95, 95% CI: 1.1, 7.86].ConclusionsDiabetic patients have higher odds of mortality, whereas no statistically significant difference of mortality was found in obese patients. Obese patients had higher odds of inhalation injury, whereas odds of inhalation injury was unchanged in diabetic patients. Diabetic patients had higher odds of failure in multiple organs, whereas such failure in obese patients was not reported. Both diabetic and obese patients had multiple complications related to infection.     

Reconstruction of skin avulsion injuries of the upper extremity with integra® dermal regeneration template and skin grafts in a single-stage procedure

Introduction

Management of skin avulsion injuries of the upper extremity may require coverage with large flaps or skin autografts. Cutaneous grafting is frequently combined with artificial skin to optimize the final functional and cosmetic result. The conventional use of bilaminated dermal substitutes consists of a two-stage procedure and requires long immobilization of the operated area. The purpose of this retrospective study is to evaluate the impact of a dermal regeneration template immediately covered by skin grafts in a one-step procedure for reconstructing skin avulsion injuries of the hand and forearm.

Materials and methods

We performed this technique in eight patients who presented with extended skin defects of the hand and forearm following skin avulsion injuries. Dimensions of the defects ranged from 160 to 1,250 cm². After debridement, Integra^® Single Layer was applied and covered with unmeshed thin skin autografts; compressive dressings were used for 1 week and mobilization started by the second postoperative week. Histological examination of the grafted areas was performed 2 weeks after surgery. Functional and cosmetic outcome was assessed 12 months postoperatively.

Results

The overall take rate of the dermal substitute and skin graft was 95-98 %. Histological results showed complete incorporation and vascular proliferation of the template, which allowed the neo-vascularization of the overlying autograft. The mean grip strength of the operated hands was at the 83 % of the normal contralateral hands. Pliability and overall appearance of the reconstructed areas was satisfactory (mean Vancouver Scar Scale Score 1.875).

Conclusions

The use of Integra^® Single Layer dermal substitute and immediate skin overgrafting consists an alternative reconstructive option for managing extended skin avulsion injuries of the upper extremity; it reduces postoperative immobilization, minimizes donor site morbidity and provides good functional and esthetic results in a single surgical procedure.