Prolonged Wound Healing Research Articles

The Limberg flap in sacrococcygeal pilonidal sinus disease

Pilonidal sinus disease can sometimes pose a surgical challenge because of prolonged wound healing problems and recurrence rates. This article describes a simple transposition flap which can be used for pilonidal sinus disease by general surgeons with good results.

Review of the Literature: Treatment of Dyspigmentation with Fractionated Resurfacing

Traditional ablative laser resurfacing is associated with adverse side effects, including prolonged erythema, edema, burning, milia, acne, crusting, and hypo- and hyperpigmentation. Fractional photothermolysis (FP) has been introduced to overcome the disadvantages of traditional ablative and nonablative resurfacing. With FP, the microscopic, pixilated pattern of wounding in the dermis results in significant skin pigmentary and textural improvements without the adverse effects of prolonged wound healing and risks of dyspigmentation associated with traditional ablative resurfacing. FP has been reported to improve hypo- and hyperpigmentation in a variety of cutaneous conditions. To review the dermatologic literature on the use of FP for treatment of dyspigmentation. Review of the Medline literature identified 35 studies on treatment of cutaneous conditions associated with dyspigmentation with ablative FP (AFP) and nonablative FP (NAFP). Specifically, we found treatment of melasma, postinflammatory hyperpigmentation, nevus of Ota, hypo- and hyperpigmented scars, poikiloderma of Civatte, laser-induced hypo- and hyperpigmentation, and dyschromia associated with photoaging. AFP and NAFP are potentially effective modalities for the treatment of dyspigmentation of the face and neck. The authors have indicated no significant interest with commercial supporters.

Arteriovenous loops in microsurgical free tissue transfer in reconstruction of central sternal defects

In some patients with chest wall defects, free tissue transfer is indicated. Complications arise if multiple operations have left the trunk devoid of recipient vessels. In such patients, an arteriovenous loop between the cephalic vein and the thoracoacromial artery can be used. A review of all our patients who underwent chest wall reconstruction with a cephalic vein-thoracoacromial artery loop between 2000 and 2009 was performed (n = 29, 19 women and 10 men). The mean age was 64.9 years. Underlying causes were sternal osteomyelitis (n = 20), tumor (n = 4), and osteoradionecrosis (n = 5). All patients were in American Society of Anesthesiologists classes III and IV. Flap selection, intraoperative and postoperative complications, operative time, time of ventilatory support, mean hospital stay, and midterm survival were recorded. Twenty-five patients received a tensor fascia lata flap, 2 a vertical rectus myocutaneuos flap, and 2 a deep inferior epigastric perforator flap. Mean duration of surgery was 6.8 hours (4.7-10.5 hours). Two transplanted tissue flaps died and/or had to be removed and 4 were revised successfully. Seven patients had wound complications such as infection or prolonged wound healing. Mean time for ventilator support was 93.6 hours (4-463 hours). The median intensive care unit time was 11 days and the overall hospital stay 27.4 days (11-102 days). One-year survival in the whole group was 69.8%. The concept of arteriovenous loops allows creation of neovessels at the recipient site and has proven to be a superb tool to facilitate free tissue transfer or to provide an exit strategy in situations with unexpected vascular problems at the recipient site.

Description of a Technique for Vacuum-Assisted Deep Drains in the Management of Cavitary Defects and Deep Infections in Devastating Military and Civilian Trauma

Deep soft-tissue defects often present in high-energy trauma and during the surgical treatment of infection. Injuries caused by high-velocity projectiles can create deep soft-tissue defects that are challenging to manage. Persistent, deep wound cavities have been associated with infection and prolonged wound healing. This article presents a technique that marries vacuum-assisted wound closure technology with traditional drains to allow for management of deep soft-tissue cavities. A deep drain was placed in the cavitary lesion with application of a negative-pressure wound therapy sponge in the standard fashion. The deep drain was brought into the sponge and fenestrated as to allow the sponge to evacuate the deep drain. Several illustrative cases are presented. Conversion of deep cavitary defects to superficial defects allowed for delayed primary or secondary closure of the wound defects without the need for increasing the size of the superficial wound to facilitate drainage. Deep infection was also successfully controlled without incurring the additional surgical soft-tissue trauma typical of standard technique. The use of the active deep suction decreases edema and dead space, theoretically reducing the chance of infection. It also prevents premature walling off of deeper cavities, which can occur with the use of vacuum-assisted closure therapy on superficial defects. Our method of wound management allows for the reduction of the deep cavitary defects without delaying wound closure or creating more tissue damage.

Correlation Between Epithelial Ingrowth and Basement Membrane Remodeling in Human Corneas After Laser-Assisted In Situ Keratomileusis

To further investigate the hypothesis that epithelial ingrowth in human corneas after laser-assisted in situ keratomileusis (LASIK) correlates with basement membrane remodeling, as suggested by the presence of matrix metalloproteinase 9 around epithelial cells in the lamellar scar. Immunohistochemical analysis and transmission electron microscopy were applied to human postmortem corneas with post-LASIK epithelial ingrowth. Epithelial ingrowth into the flap margin was observed in 8 of 18 corneas (44%). Matrix metalloproteinase 9 immunolocalized around ingrown epithelium in 6 of these 8 corneas (75%). There was a positive correlation between the presence of matrix metalloproteinase 9 at the wound margin and discontinuities in the basement membrane, as determined by laminin and beta(4) integrin immunofluorescence. Transforming growth factor beta2 was present into the stroma of some corneas with epithelial ingrowth and interrupted basement membrane, suggesting some degree of epithelial-stromal interaction. Transmission electron microscopy confirmed large areas of remodeled basement membrane along ingrown epithelial cells. The neo-basement membrane components underlying the ingrown cells in human corneas with epithelial ingrowth after LASIK appear to be partially disassembled. Epithelial-stromal interaction over time may be related to prolonged wound healing remodeling, which calls into question the stability of the flap.

Resin splint as a new conservative treatment for ingrown toenails

Several conservative as well as surgical methods are used for the treatment of ingrown toenails until date. The conservative methods are either based on nail splinting or on orthonyxia, but no methods employing both principles have been reported thus far. Moreover, surgical methods usually involve postoperative pain, prolonged wound healing and restricted activities of daily living. Therefore, considering the need of a simplified, non-invasive method, in this study, we applied a novel splint to treat patients with ingrown toenails and estimated the clinical efficacy as well as rate of recurrence following treatment. The splint is a plate made of resin that is attached to the lateral edge of the nail using a bandage. We studied 61 patients (19 men and 42 women; mean age 36 years), with an average application duration of 9.3 months and an average follow-up period of 10 months in all patients. All patients experienced pain relief within a week of splint application and a decrease in the degree of nail deformity. Moreover, follow-up revealed a recurrence rate of 8.2%. Therefore, we believe that this new device is an excellent conservative treatment method for patients with ingrown toenails.

Long-term evaluation of donor site morbidity after free fibula transfer

Our aim was to evaluate the long-term morbidity at the donor site after harvest of free fibular flaps. From a total of 165 patients, we were able to examine (not randomly) 62 donor regions in 57 patients (33 men and 24 women) 2–167 months (mean 45 months) after fibular transfer. Patients’ individual risk factors and any disturbances of healing, and dysfunction of the toes, were recorded. The Kitaoka ankle–hindfoot score was used for evaluation of functional impairment. Thirteen donor regions displayed prolonged wound healing, eight of which needed revision of the wounds. Eight (14%) had abnormalities of gait. The median Kitaoka ankle–hindfoot score was 93 (range: 14–100). In 17 patients (27%) after a follow-up period of 4 months, hammer and claw toes and deficits in dorsal extension of the hallux were assessed. Thirty patients (48%) had sensory deficits of the calf and toes. Neither the risk factors recorded nor the factors that indicated disturbance of wound healing or deformities of the toe were significantly associated with the development of functional impairment. In more than three-quarters of the cases healing was uneventful, but in a small number the morbidity at the donor site was severe, forcing the patient to use walking aids. We were not able to identify any risk factors for the development of long-term malfunction.

Influences of interferon-gamma on cell proliferation and interleukin-6 production in Down syndrome derived fibroblasts

Objective Down syndrome, a frequently encountered genetic disorder, is usually associated with medical problems related to infectious disease, such as periodontal diseases and prolonged wound healing. Although affected individuals are considered to have clinical problems related to high interferon (IFN) sensitivity, the molecular mechanisms of IFN activities are not completely understood. Design Down syndrome derived fibroblasts, Detroit 539 (D1) and Hs 52.Sk (D2) cells, were used. To analyse the expressions of interferon (IFN) receptors and downstream of IFN-γ, western blotting was performed. Cell proliferation was determined by counting cells following trypan blue staining. Media levels of IL-1β, TNF-α, and IL-6 were quantified using ELISA. Results IFN-γ receptor 2 and IFN-α receptor 1, but not IFN-γ receptor 1, were highly expressed in D1 and D2 cells, as compared to the control fibroblast cells. Cell proliferation by D1 and D2 cells was lower than that by the control fibroblasts, further, IFN-γ had a greater effect to inhibit cell proliferation by D1 and D2 cells. In addition, IFN-γ treatment increased the phosphorylation of STAT1 and MAPK in D1 cells as compared to normal fibroblasts. Also, the presence of exogenous IFN-γ in the growth medium significantly induced IL-6, but not IL-1β or TNF-α, in D1 and D2 cells. Conclusion Taken together, our results are consistent with hypersensitive reactions to IFN-γ seen in patients with Down syndrome and may provide useful information to elucidate the mechanisms of IFN-γ activities in those individuals.

Balloon Dilatational Tracheostomy: Initial Experience with the Ciaglia Blue Dolphin Method: Retracted

Percutaneous dilational tracheostomy has become an established technique for ensuring safe and uncomplicated access to the respiratory systems of patients undergoing prolonged intubation. We studied a new balloon dilation percutaneous dilational tracheostomy technique which primarily uses radial force to widen the tracheostoma, the Ciaglia Blue Dolphin system. We report our initial clinical experience with this method in 20 patients from a cardiosurgical intensive care unit. We analyzed the results with regard to the practical feasibility of balloon dilation as well as possible complications. Tracheostomy surgery time averaged 3.3 +/- 1.9 min. The new technique caused neither bleeding requiring treatment nor injuries of the posterior tracheal wall. Routine bronchoscopic checks revealed one fracture of a single tracheal cartilage ring (5%). One patient developed subcutaneous emphysema during the balloon dilation, but this regressed spontaneously without treatment. No wound infections or prolonged wound healing of the tracheostoma were observed in any patient. There were no differences in terms of practical feasibility or bleeding complications when skin incisions of different lengths were analyzed. The balloon dilational tracheostomy proved to be a feasible, easy, and successful technique. Its use of mainly radial force may reduce typical complications such as fractures of tracheal cartilage rings or injuries of the posterior tracheal wall.

Disorders of perioperative heat balance and their treatments

The importance of diagnosing and preventing intraoperative hypothermia has come into the focus of interest in the past decade. It has been proved that core temperature decreases by 1-3 degrees C during the course of long-time anesthesias. As well as it has been proven that even mild hypothermia (core temperature less than 36 degrees C) leads to numerous perioperative complications influencing the outcome of the patients, such as perioperative cardiac abnormalities, increased bleeding risk and need for transfusion, decreased metabolism of the medications as well as prolonged wound healing process. It is also clear that treatment of intraoperative hypothermia may double the perioperative costs. Therefore, in the present review we intend to summarize the recent knowledge on the development, consequences and prevention of intraoperative hypothermia.

A Detailed Comparison of the Functional Outcome After Midforearm Replantations Versus Midforearm Transplantation

Objectives The functional outcome after midforearm transplantation (HT) is believed to be similar to the outcome after replantation. However, the few existing reports comparing functional outcomes are based on amputations at the level of the distal forearm. This report provides a comparative analysis of the functional results after midforearm replantation (HR) versus HT. Materials and Methods Transplantation of a dominant right forearm performed in a 32-year-old man was compared to the outcomes after five dominant (right) forearm replantations (four men and one woman) in patients ranging from 22 to 38 years of age. Cold ischemia time ranged from 6 to 12.5 hours in all cases. We used similar operative technique and rehabilitation protocol. At 26 (±2) months after replantation/transplantation, we recorded, bony union (x-ray), arterial flow (ultrasonography), range of motion, grip strength, sensation (2 PD Weisensten's filaments), quality of life (DASH, 30–150 points), general evaluation of function according to Chen's or the IRHCTT scoring system. Results A complication of wound infection was observed in one HR patient; Marginal skin necrosis accompanied by prolonged wound healing, in one HT patient. Unification of bones was achieved faster after forearm replantation when compared with transplantation. Grip strength was 17% greater after replantation, but ranges of motion were comparable in both groups. Sensitivity was superior after forearm transplantation (2 PD 15 mm) and overall patient satisfaction was comparable (90 points of DASH questionnaire for HR versus 108 points for HT patients). None of the patients returned to their previous occupations. Conclusion The functional outcome after HT was comparable, and in some respects superior, to the outcome after replantation performed at the midforearm level.

Inguinal hernia repair with the peduncled fascial flap: a new surgical technique

This paper presents a new surgical technique of inguinal hernia repair in which both crura of the aponeurosis of the external oblique abdominal muscle and transverse fascia were used for complex reconstruction of the entire musculopectineal hiatus. Between 2nd December 2003 and 29th April 2005, 250 patients (233 male and 17 female) underwent inguinal hernia repairs using our own technique. The inguinal canal was opened together with the posterior wall, dividing the transverse fascia into two flaps. The lower flap was inserted into the femoral opening and sewn to the pectineal ligament, whereas the upper flap with both crura of the aponeurosis of the external oblique abdominal muscle were used for three-fascia reconstruction of the posterior wall of the inguinal canal. The study group was randomly chosen from patients undergoing surgery due to inguinal hernias in our hospital. Procedures were carried out under subarachnoid anaesthesia; postoperative pain was treated with methamizol or ketoprofen. Patients were discharged 48 h after surgery. The postoperative complications included one hernia recurrence and one testicular atrophy. The remaining complications were transient and included prolonged wound healing, transient skin hypoaesthesia around the wound or testis oedema. The technique used strengthens the musculopectineal hiatus, effectively preventing recurrences of inguinal as well as femoral hernias.

Perineale Hernie

Abdominoperineal excision of the rectum is a standard procedure in deep-lying rectal cancer if the sphincter muscle cannot be preserved. Besides common complications such as impotence, disorders of urinary tract function, and prolonged wound healing, perineal hernia is a rare long-term phenomenon. Surgical repair can be done either through a transabdominal approach or transperineally. Long-term results show that both methods are feasible in this situation. We report the third case of perineal hernia in German literature. A 66-year-old man presented with a painful perineal tumor 2 years after abdominoperineal excision for rectal adenocarcinoma. Perineal hernia was confirmed by magnetic resonance imaging, and the patient underwent open mesh repair through a perineal approach. A number of surgical techniques have been described for the repair of perineal hernias. These include abdominal, perineal, and combined or laparoscopic approaches with or without mesh repair. The transabdominal route seems to have some advantages over the perineal approach. In cases of small hernias, the latter can however be the option of choice. In the presented case of an uncomplicated hernia, we decided on the perineal approach including mesh implantation to keep the trauma as small as possible.

Genetic Background of Venous Leg Ulcer Development

Fibroblast growth factor receptor 2 gene codes for IIIb and IIIc transcript variants, which play pivotal roles in normal wound healing. Tumor necrosis factor α mediates several biological processes including wound healing. We aimed to characterise the expression pattern of IIIb expressed by in vitro cultured keratinocytes and in skin biopsy samples of venous leg ulcer patients, and to identify polymorphisms which may play a role in the pathomechanism of prolonged wound healing in venous leg ulcer patients. Real-time reverse transcription polymerase chain reaction and Western blotting methods were used for expression studies, polymerase chain reaction with TaqMan probes and with restriction fragment length polymorphism method were performed for polymorphism studies. We demonstrated that the expression of IIIb is related to the proliferation states of HaCaT keratinocytes and its expression is down-regulated in the uninvolved epidermis of venous leg ulcer patients ( n = 15) compared to the epidermis of controls ( n = 15). We identified a polymorphism in the 3’ untranslated region (2451A/G) of the fibroblast growth factor receptor 2 gene, which displayed a significant difference in the allelic distribution between leg ulcer patients ( n = 82) and controls ( n = 82; p = 0.0103). We hypothesize that this polymorphism may be a susceptibility factor for venous leg ulcer. In another set of experiment we demonstrated that the A allele of the –308 tumor necrosis factor α polymorphism might be a potential factor for venous leg ulcer susceptibility; however, our data suggest that this association is secondary and the primary association probably exists with obesity.

Expanded HSAN4 phenotype associated with two novel mutations in NTRK1

Hereditary sensory and autonomic neuropathy type IV (HSAN4) is a severe autosomal recessive disorder characterized by childhood onset of sensory and autonomic dysfunction leading to hyperthermia, recurrent infections and physical impairment due to complications of osteoarthritis. Cognitive impairment and aggressive behaviour is common. HSAN4 is caused by mutations in the NTRK1 gene coding for the tyrosine kinase receptor A. We present detailed description of a rare, mild HSAN4 phenotype associated with two novel NTRK1 mutations. This Swedish patient presents with an adult onset of painful Charcot arthropathy, prolonged wound healing, discrete polyneuropathy, hypohidrosis without further autonomic dysfunction and no cognitive affection.

OK-432 as a Sclerosing Agent to Treat Wound-Healing Impairment

We report on the application of OK-432 (picibanil) in a patient with prolonged wound healing impairment. A 13-year-old girl had suffered a polytrauma with a displaced fracture of the sacrum which required neurosurgical decompression of the sacral plexus. Postoperatively, a seroma with recurrent fistulation was seen. Excision of the wound, prolonged suction drainage and the instillation of hypertonic glucose solution did not have any effect over a period of four months postoperatively. Relying on our personal experience of the treatment of lymphangiomas using OK-432 we instilled OK-432 into the wound. Leakage stopped immediately, there was a regression of fluid accumulation and four weeks later the ultrasound examination was normal. The patient is still asymptomatic four years after treatment. OK-432 can be used effectively for the treatment of chronic wound healing impairment.

Management of Morel-Lavallee Lesion Associated with Pelvic and/or Acetabular Fractures.

Management of Morel-Lavallee soft tissue lesion (MLL) in patients with associated pelvic and/or acetabular fractures is still under discussion. Especially, the sequence of treatment of MLL soft tissue management and osteosynthesis of pelvic and acetabular injury remains controversial. We report all consecutive patients with MLL associated with pelvic ring and/or acetabular fractures during an 8-year period at our hospital. Surgical access and techniques were analyzed concerning complications and outcome. Altogether, 20 patients were included in the study. One patient was treated conservatively and MLL healed without complications; 19 patients had an operative treatment of MLL. In 15 patients debridement was performed within one day after injury and in four patients with delay of 5 days at least. Ten patients had surgery for an associated pelvic ring or acetabular fracture. In four of them MLL was operated before, in six patients simultaneously to osteosynthesis. In three patients, the same surgical approach for osteosynthesis and debridement of MLL was used; none of them showed postoperative complications. Altogether, in nine operated patients (47.4%) MLL healed without any complications. Nine operated patients presented prolonged wound healing, however, during long term follow-up, all patients showed complete healing of the MLL. One patient died during resuscitive surgical procedures. We recommend debridement for early and delayed treatment of MLL. Osteosynthesis during first debridement may be performed without adverse outcome. Identical surgical access for both procedures can be used. In case of repeated surgical debridement VAC(®) therapy may be a helpful tool for dead space reduction and wound conditioning.

Syk-mediated translocation of PI3Kdelta to the leading edge controls lamellipodium formation and migration of leukocytes.

The non-receptor tyrosine kinase Syk is mainly expressed in the hematopoietic system and plays an essential role in β2 integrin-mediated leukocyte activation. To elucidate the signaling pathway downstream of Syk during β2 integrin (CD11/CD18)-mediated migration and extravasation of polymorphonuclear neutrophils (PMN), we generated neutrophil-like differentiated HL-60 (dHL-60) cells expressing a fluorescently tagged Syk mutant lacking the tyrosine residue at the position 323 (Syk-Tyr323) that is known to be required for the binding of the regulatory subunit p85 of the phosphatidylinositol 3-kinase (PI3K) class IA. Syk-Tyr323 was found to be critical for the enrichment of the catalytic subunit p110δ of PI3K class IA as well as for the generation of PI3K products at the leading edge of the majority of polarized cells. In accordance, the translocation of PI3K p110δ to the leading edge was diminished in Syk deficient murine PMN. Moreover, the expression of EGFP-Syk Y323F interfered with proper cell polarization and it impaired efficient migration of dHL-60 cells. In agreement with a major role of β2 integrins in the recruitment of phagocytic cells to sites of lesion, mice with a Syk-deficient hematopoietic system demonstrated impaired PMN infiltration into the wounded tissue that was associated with prolonged cutaneous wound healing. These data imply a novel role of Syk via PI3K p110δ signaling for β2 integrin-mediated migration which is a prerequisite for efficient PMN recruitment in vivo.

A Combined Approach to Pain Management in the Surgical Neonate

Over the past decade, survival rates of preterm and acutely ill infants who have gastrointestinal (GI) anomalies or diagnoses that require surgical treatment in the neonatal intensive care unit (NICU) have improved dramatically. However, despite the technological advances, morbidity rates including neurosensory deficits, cognitive delays, and motor impairments remain high. Because these compromised infants are surviving the diagnoses and concomitant surgery, it behooves caregivers and researchers to identify caregiving practices that can be combined with existing treatment modalities to maximize long-term outcomes for infants and families and minimize the pain associated with the diagnosis, surgery, investigative tests, and ongoing treatment. Recent studies have shown that when infant pain is not recognized and/or left untreated, immediate and long-term consequences ensue. Severe unrelieved pain can cause an overwhelming stress response, which can lead to serious complications including prolonged wound healing, increased need for assisted ventilation, and death. Infants are particularly vulnerable to the undertreatment of pain because they cannot report or describe their pain the way older children and adults can. Theymust rely on their caregivers' ability to interpret their cues of pain, manage it appropriately, and when possible, prevent it. Infants have the necessary neurotransmitters to transmit pain, but they have poorly developed mechanisms by which to inhibit the negative effects. Their inability to modulate the negative effects of pain are affected by gestational age and severity of illness, thereby placing the most vulnerable infants at highest risk for consequences of prolonged pain. Despite ample evidence to support infants' ability to experience pain, the provision of timely and adequate analgesia is fraught with

Overweight induced by high-fat diet delays rat cutaneous wound healing

Prolonged wound healing is a complication that contributes to morbidity and mortality. Overweight people regularly undergo surgery and trauma, and often develop chronic wounds, but the effects of the adipose tissue excess on cutaneous wound healing are not well understood. This study tested the hypothesis that overweight induced by a high-fat diet impairs rat cutaneous wound healing. Male Wistar rats were fed with either a high-fat or a standard (control) diet. After 15 weeks, an excisional lesion was done and the animals were killed 21 d later. Wound contraction and re-epithelialization, blood pressure, glucose and retroperitoneal fat were evaluated. After killing, lesion and adjacent normal skin were formol-fixed and paraffin-embedded. Inflammatory infiltrate, myofibroblasts, collagen fibres and cellular proliferation were analysed and blood vessels were evaluated using stereological methods. There was no difference in blood pressure and glucose, but retroperitoneal fat increased in the high-fat diet group. Animals fed with the high-fat diet presented delayed wound contraction and re-epithelialization. It was found that 21 d after wounding, overweight induced by a high-fat diet increased the inflammatory infiltrate and delayed myofibroblastic differentiation, collagen deposition, epithelial and connective tissue cell proliferation, and angiogenesis. These findings support the hypothesis that a high-fat diet exerts negative effects on rat cutaneous wound healing, due mainly to the prolongation of the inflammatory phase.