Prolonged Wound Healing Research Articles

Connexin 43 Antisense Therapy Modulates Connexin Expression and Wound Repair in Nitrogen Mustard Injured Mouse Skin

Connexin 43 (Cx43) antisense treatment accelerates diabetic skin wound repair. Cx43 expression and its phosphorylation (pCx43) alters gap junction communication during skin wound repair. Vesicant induced skin injury results in prolonged wound healing similar to diabetic wounds. We performed a time course study using Cx43 antisense oligodeoxynucleotides (asODN) on nitrogen mustard (NM) injured SKH-1 hairless mouse dorsal skin to evaluate wound progression and Cx expression. Immunofluorescent (IF) analysis of NM injured skin demonstrated increased keratin 17 (K17, skin wound marker), increased expression of Cx26 and pCx43, and minimal expression of Cx43 by day 1. All markers were up-regulated with time as the wounds progressed. Dual-labeling studies indicated strong expression of Cx26 near the leading edge of wounds. In contrast, Cx43 and pCx43 were highly expressed in the hyperplastic epithelium. Cx43asODN treatment improved NM wounded skin as indicated by minimal K17 expression at day 1. Western blotting showed reduced levels of Cx43 and pCX43 over time. Dual labeling demonstrated that Cx43 asODN treatment successfully reduced Cx43 and pCx43 expression and it was mostly restricted to the basal keratinocytes. Cx26 expression appeared more prevalent in both the wound margin and hyperplastic epithelium by day 3. We hypothesize that the increased epidermal Cx26 positive area is associated with migratory keratinocytes to improve epithelialization. In conclusion, Cx43asODN altered the Cx expression profile, modulated gap junction communication and accelerated vesicant wound repair. Supported by ES005022, EY09056, and NIAMS U54AR055073.

Local full-thickness skin graft of the donor arm—a novel technique for the reduction of donor site morbidity in radial forearm free flap

A novel technique to reduce donor site morbidity after radial forearm free flap (RFFF) harvest, using a local full-thickness skin graft (FTSG), is described. Thirty consecutive patients undergoing RFFF for head and neck reconstruction were enrolled in a prospective study. Donor site defect closure was performed with spindle-shaped FTSGs excised from the wavelike skin incision made for the vascular pedicle. Both the removal site of the FTSG on the volar forearm and the covered RFFF donor site healed uneventfully in 29 cases, with no impairment of function related to the skin graft. No skin graft failure and no exposure, tenting, or adherence of the flexor tendons occurred. All patients expressed satisfaction with postoperative pain, the functional outcome, and cosmetic appearance. Primary donor site defect closure could be achieved in all cases with the use of a local FTSG. This graft can be gained at the access incision for the vascular pedicle, avoids expansion of the incision for a local flap technique, and does not prolong wound healing, and thus reduces both donor site and graft site morbidity of the RFFF. This technique leads to an inconspicuous aesthetic result with no apparent relevant functional deficits and avoids the need for a second donor site.

Outcomes of the house advancement flap for pilonidal sinus.

Many surgical techniques have been described for the treatment of pilonidal sinus, yet rates of recurrence and prolonged wound healing remain high and consensus on the optimal technique is lacking. This retrospective study evaluates outcomes of the use of the house advancement flap in the treatment of pilonidal sinus including time to wound healing, sinus recurrence, wound infection and flap necrosis. Thirty-three consecutive patients who underwent excision and house advancement flap for pilonidal sinus, of whom seven patients (21%) had recurrent pilonidal sinus disease following previous surgical intervention, were reviewed retrospectively. Follow-up ranged from 4 to 59 months (mean 28 months). All 33 patients completed a follow-up survey. Age at time of operation ranged from 14 to 44 years with a mean of 25 years. No patients developed wound infection or flap necrosis. Four patients (12%) failed to achieve primary wound healing; mean time to wound healing for the remaining 29 patients was 62 days. Recurrence of pilonidal sinus occurred in eight patients (24%), at a mean time of 22 months post-operatively. The house advancement flap achieves primary wound closure in almost 90% of cases with few acute post-operative complications. However delayed wound healing and sinus recurrence remain issues with this technique and it appears to have little advantage over other primary closure techniques.

Dynamics of wound healing signaling as a potential therapeutic target for radiation-induced tissue damage.

We hypothesized the histone deacetylase inhibitor phenylbutyrate (PB) has beneficial effects on radiation-induced injury by modulating the expression of DNA repair and wound healing genes. Hamsters received a radiosurgical dose of radiation (40 Gy) to the cheek and were treated with varying PB dosing regimens. Gross alteration of the irradiated cheeks, eating function, histological changes, and gene expression during the course of wound healing were compared between treatment groups. Pathological analysis showed decreased radiation-induced mucositis, facilitated epithelial cell growth, and preventing ulcerative wound formation, after short-term PB treatment, but not after vehicle or sustained PB. The radiation-induced wound healing gene expression profile exhibited a sequential transition from the inflammatory and DNA repair phases to the tissue remodeling phase in the vehicle group. Sustained PB treatment resulted in a prolonged wound healing gene expression profile and delayed the wound healing process. Short-term PB shortened the duration of inflammatory cytokine expression, triggered repeated pulsed expression of cell cycle and DNA repair-regulating genes, and promoted earlier oscillatory expression of tissue remodeling genes. Distinct gene expression patterns between sustained and short-term treatment suggest dynamic profiling of wound healing gene expression can be an important part of a biological therapeutic strategy to mitigate radiation-related tissue injury.

Histological study on the effect of topical application of glucosamine on wound healing in rats

Introduction Wounds are common in clinical practice, both in outpatient clinics and in hospitals. Poor and/or prolonged wound healing is a clinical problem resulting in long hospital stay and considerable economic costs. Glucosamine (GA) is a water-soluble hexosamine derived from chitin or chitosan. It has been shown to have a stimulatory effect on matrix formation and hyaluronic acid synthesis. However, these results were mainly through systemic administration, with few studies topically conducted. The aim of this study was to determine the effect of topical administration of GA on the wound healing process in a rat model of full-thickness skin wounds. Materials and methods Twenty-four male albino rats were divided into two groups: a control group (group I) and an experimental group (group II). The control group (10 rats) received regular dressing in addition to the nonmedicated gel base. The experimental group (14 rats) received 2% GA in gel form. A 1 cm2 full-thickness skin wound was created on the back of each rat. Treatment was administered daily until the end of the study (for 10 days). The wound closure rate, collagen synthesis, blood vessel formation, and fibroblast proliferation were studied by histological, immunohistochemical, and morphometric methods. Results GA significantly enhanced and accelerated the wound closure rate as well as fibroblast proliferation. Collagen synthesis was also enhanced, as well as proliferation of hair follicles, in contrast to the control group. GA also improved the neovascularization process at the wound site. Overall, topical application of 2% GA accelerated the wound healing process and the wound contracting ability. Conclusion The results of this study indicated that GA has the potential to be used for treatment of skin wounds as a topical medication; however, further evaluations of its mechanisms of action and its clinical disadvantages should be made.

English

In the past, any surgical procedures of infants and young children was completed under general anesthesia, after obtaining a medical clearance for hospital admission thus consuming lot of time which potentially introduce the child to a greater risk during general anesthesia. Traditionally methods of using scalpels or electro surgery may produce significant post-operative discomfort, requiring sutures –prolonged wound healing. Thus lasers provide simple, significant and safe in office alternative for children.

Retrospective Analysis of Hemoglobin A1C Levels in Plastic Surgery Patients with Post-Operative Morbidity

PURPOSE: According to the Centers for Disease Control and Prevention, the prevalence of diabetes has been steadily increasing in the United States. In 2010, based on fasting blood glucose or hemoglobin A1C levels, 11.3% of the population over age 20 had been diagnosed with diabetes with an additional 35% labeled as pre-diabetic. Among the known morbidities of diabetics is an increased risk for post-surgical complications such as infection and prolonged wound healing. Current literature recommendations in orthopedics and urology vary with threshold A1C levels ranging from 6.7 to 11.5 (respectively) to decrease complications. To optimize patient safety, a more precise target is ideal for the plastic surgery population undergoing elective procedures. METHODS: A retrospective chart review analyzed patients who underwent plastic surgery from January 2006-December 2013 (n=26327) in an academic practice at a Level I trauma center. The patients who subsequently developed periprosthetic or surgical site infections, wound healing difficulties or dehiscences, or fluid collections were identified. Data was analyzed to identify a trend in A1C levels as related to complications. RESULTS: A total of 981 patients (3.7% of patients from 1/2006-12/2013) with post-surgical complications were reviewed with 471 patients (1.8%) having documented diabetes. Forty-four diabetics were identified with an A1C level within 3 months of initial surgery or complication presentation (9.7%). The mean A1C level was 7.0 with a standard deviation of 2.0. In our patients with complications, 79% were between the ages of 50-60 years old. The majority of complications in patients with an A1C>6.5 was infectious (53%). Fasting glucose levels at the time of initial surgery were found to be elevated in 63% of patients with surgical site and periprosthetic infections when compared to patients suffering from delayed wound healing and wound dehiscence irrespective of age and A1C. CONCLUSIONS: According to our study, hemoglobin A1C levels in diabetic patients over 7.0 can have a clinically significant link to post-operative complications. This preliminary study of long-term glycemic control and surgical complications will potentially help establish new surgical guidelines and pre-operative management of plastic surgery patients. It is imperative that more data is collected and more stringent documentation is implemented to precisely elucidate the link between A1C levels and post-surgical complications in our diabetic population which makes up nearly half of our practice’s morbidity.

Challenging Diagnosis of a Rare Case of Spontaneous Keloid Scar

Keloid scars are benign dermal collagenous lesions that arise in the reticular layer of the dermis as a result of a period of prolonged wound healing due to injurious cutaneous insult. It is diagnosed clinically by a history of injury preceding its appearance and its pathognomonic encroachment beyond the boundary of the original wound. There are multiple factors that predispose an individual to keloid scar formation but no single hypothesis sufficiently explained its complex pathogenesis. The spontaneity of keloid scar to arise de novo without prior cutaneous injury is very rare. Although the non-specific appearance of spontaneous keloid scar can resemble various malignant or benign tumors, it is of paramount importance to accurately diagnose it due to the difficulty and complexity of keloid scar treatment or the atrocious outcome of its mismanagement. Here, we presented a rare case of spontaneous keloid scar over an unusual site of occurrence, and its disfiguring consequences as a result of misdiagnosis and treatment. We also highlighted the diagnostic challenge facing many clinicians when spontaneous keloid scar occurred in an individual without significant predisposing factors. Therefore, extra vigilance should be exercised in our practice and the spontaneity origin of keloid scar should be borne in one’s mind. J Med Cases. 2014;5(8):466-469 doi: http://dx.doi.org/10.14740/jmc1887w

Reconstruction of the external auditory canal using the random flap technique and laser Doppler evaluation.

The external auditory canal is one of the most difficult sites to reconstruct after tumor resection. In general, fascia transplantation is used to reconstruct defects of the external auditory canal, but this method is associated with scar formation and prolonged wound healing. Scar tissue might cause stenosis in the external auditory canal and hypoacusis, and wound healing is further delayed by radiation and chemotherapy. To examine the safety of a random flap for reconstruction of an external auditory canal based on blood flow evaluation using a laser Doppler system. Ten healthy volunteers were enrolled in this study to compare blood flow in the face, back, and behind the ear using a laser Doppler system. Two cases of external auditory canal reconstruction are presented. Blood flow behind the ear was abundant compared with that in the back. Blood flow in the face was higher than that behind the ear or on the back. Blood flow in the random flap was easily evaluated using the laser Doppler method. Based on our findings, we propose the random flap to reconstruct the external auditory canal after tumor resection.

Neutrophil depletion in the early inflammatory phase delayed cutaneous wound healing in older rats: improvements due to the use of un-denatured camel whey protein

BackgroundWhile it is known that advanced age alters the recruitment of neutrophils during wound healing, thereby delaying the wound healing process, little is known about prolonged wound healing in advanced ages. Thus, we investigated the correlation of neutrophil recruitment with healing events, and the impact of whey protein (WP) on neutrophil activation.MethodsThe animals were allocated into wounded young group, wounded older group and wounded older rats with daily treatment of WP at a dose of 100 mg/kg of body weight.ResultsOur results pointed to a marked deficiency in the number of neutrophils in the wounds of older rats, which was accompanied with impairment of the healing process. In the group of older rats, phagocytic activity, as tested by fluorescence microscopy, declined throughout the first 24 hours after wounding. Both the neutrophil number and the phagocytic activity recovered in older rats which received WP supplementation. Interestingly, WP was found to significantly up-regulate the MIP-1α and CINC-1 mRNA expression in old rats. On the other hand, the wound size in older rats was significantly higher than that in younger ones. Blood angiogenesis was also significantly delayed in the older group as opposed to the young rats. WP, however, was found to return these indices to normal levels in the older rats. Proliferation and epidermal migration of the keratinocytes and the collagen deposition were also returned to the normal rates.ConclusionsThis data confirms the critical role of neutrophil recruitment in the early inflammatory phase of wound healing in older rats. In addition, WP protein was used to improve neutrophil function in older rats, healing events returned to a more normal profile.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2100966986117779.

CP-055 Effect of rivaroxaban on wound healing after elective tibial osteotomy

BackgroundAfter elective tibial osteotomy patients are considered at high risk of venous thromboembolism (VTE) due to prolonged immobilisation. Routine pharmacological thromboprophylaxis for these patients is widely adopted in clinical practice...

Challenging Diagnosis of a Rare Case of Spontaneous Keloid Scar

Keloid scars are benign dermal collagenous lesions that arise in the reticular layer of the dermis as a result of a period of prolonged wound healing due to injurious cutaneous insult. It is diagnosed clinically by a history of injury preceding its appearance and its pathognomonic encroachment beyond the boundary of the original wound. There are multiple factors that predispose an individual to keloid scar formation but no single hypothesis sufficiently explained its complex pathogenesis. The spontaneity of keloid scar to arise de novo without prior cutaneous injury is very rare. Although the non-specific appearance of spontaneous keloid scar can resemble various malignant or benign tumors, it is of paramount importance to accurately diagnose it due to the difficulty and complexity of keloid scar treatment or the atrocious outcome of its mismanagement. Here, we presented a rare case of spontaneous keloid scar over an unusual site of occurrence, and its disfiguring consequences as a result of misdiagnosis and treatment. We also highlighted the diagnostic challenge facing many clinicians when spontaneous keloid scar occurred in an individual without significant predisposing factors. Therefore, extra vigilance should be exercised in our practice and the spontaneity origin of keloid scar should be borne in one’s mind. J Med Cases. 2014;5(8):466-469 doi: https://doi.org/10.14740/jmc1887w

Outcomes and Safety of Endoscopic Tarsal Tunnel Decompression

Open surgical decompression of the tarsal tunnel is the standard surgical approach for compression of the tibial nerve within the tarsal tunnel. Complications associated with this approach can be significant and periods of non-weight bearing are required. An alternative approach allowing for minimal soft tissue trauma and reduced time to ambulation is therefore desirable. Endoscopic tarsal tunnel decompression may provide such an alternative. The authors performed a systematic review of electronic databases and other relevant sources to identify material regarding the safety of endoscopic tarsal tunnel decompression. Only articles that included clear information concerning the safety of endoscopic tarsal tunnel decompression with a follow-up of at least 12 months were included. Three studies were identified involving 37 feet, with a weighted mean follow-up of 27 months. There were no permanent complications relating to iatrogenic nerve injury, deep infection, or prolonged wound healing problems documented despite initiating ambulation within one week of surgery. Two patients (5.6%) developed recurrence more than 2 years postoperative and one (2.7%) showed no improvement. Endoscopic tarsal tunnel decompression is a safe procedure with a low rate of recurrence or failure and allows for near-immediate ambulation. However, additional prospective investigations comparing open and endoscopic approaches to tarsal tunnel decompression are warranted.

The role of nutrition in preventing pressure ulcers

Old age, pressure ulcers and malnutrition may co-exist. Wounds in older people may already be slow to heal as a result of compromised skin integrity, which occurs as part of the normal ageing process. Malnutrition is also more common in older people, and evidence has shown that inadequate nutrition may lead to impaired and prolonged wound healing. This article explores the relationship between nutrition and wound healing, and promotes optimum nutrition in old age as an essential component of effective wound management.

Calcanectomy: Avoiding major amputation in the presence of calcaneal osteomyelitis—A case series

BackgroundCalcaneal osteomyelitis is a surgical diagnosis that may be treated by local, resection or major amputation. ObjectiveTo determine the effectiveness of calcanectomy for treating calcaneal osteomyelitis. MethodWe conducted a retrospective review of patients receiving calcanectomy between 1st April 2005 and 1st October 2011 for calcaneal osteomyelitis. We reviewed these cases to determine healing, rate, microbiological analysis, length of stay, limb salvage rate and survival rate. ResultsThere were 10 patients included in this review. There were 7 with diabetes and 3 without.Mean age of group with diabetes was 64 years, of this group 5/7 healed at a mean of 64 days. Mean length of stay for this group was 49.3±39.4 days. 2 patients required a transtibial amputation. Mean age of group without diabetes was 77 years, healing at a mean of 19 days. Mean length of stay for this group was 14±16.8 days and all survived over 3 years. Microbiological analysis of suspected osteomyelitic bone typically isolated >4 organisms. ConclusionsCalcanectomy is a useful procedure for limb salvage. It may reduce morbidity rates for people with calcaneal osteomyelitis, those with diabetes can expect prolonged wound healing and longer length of stay.

Local Recurrence Patterns in Breast Cancer Patients Treated with Oncoplastic Reduction Mammaplasty and Radiotherapy

The purpose of this study was to describe the incidence and location of ipsilateral breast tumor recurrence (IBTR) among breast cancer patients treated with oncoplastic reduction mammoplasty (ORM) and radiotherapy (RT). The medical records of 86 consecutive women with ductal carcinoma in situ (DCIS) (n = 11) or invasive carcinoma of the breast (n = 75) treated with ORM at Emory University between January 1994 and December 2010 were reviewed. Following ORM, prolonged wound healing or surgical complications led to delay of adjuvant chemotherapy or RT in 11 patients. Surgical clips were found outside the primary tumor breast quadrant in 43 % of the patients with available RT planning CT images. When the clips were found outside the primary tumor quadrant, the RT boost was more frequently delivered outside versus inside the primary tumor quadrant (67 vs. 33 %, p < 0.001). After a median follow-up period of 4.5 years (range 0.1-17.9), 6 patients developed an IBTR and only 1 IBTR occurred outside the primary tumor quadrant. The 5-year ipsilateral breast tumor control rates were 91 % (95 % CI 0.82-0.99) and 93 % (95 % CI 0.90-0.97) for patients with DCIS and invasive carcinoma, respectively. The use of ORM yields acceptable rates of IBTR. ORM may displace breast tissue and surgical clips to breast quadrants outside of the original tumor location, but the majority of IBTRs still occur in the original tumor quadrant. This area remains at highest risk of in-breast recurrence in women treated with ORM irrespective of surgical clip location.

Management of pediatric penile keloid

Keloids are abnormal scar tissue growths that extend beyond the original area of injury, occasionally occurring post-surgery. Risk factors for keloids include skin trauma, infection, prolonged wound healing and individuals of certain ethnicities. Keloid formation on the penis, however, is a rare occurrence even among circumcised males, and can produce both aesthetic and functional complications. We document the tenth patient in the literature, to our knowledge, to present with a keloid of the penis.

Predicting complex acute wound healing in patients from a wound expertise centre registry: a prognostic study

It is important for caregivers and patients to know which wounds are at risk of prolonged wound healing to enable timely communication and treatment. Available prognostic models predict wound healing in chronic ulcers, but not in acute wounds, that is, originating after trauma or surgery. We developed a model to detect which factors can predict (prolonged) healing of complex acute wounds in patients treated in a large wound expertise centre (WEC). Using Cox and linear regression analyses, we determined which patient- and wound-related characteristics best predict time to complete wound healing and derived a prediction formula to estimate how long this may take. We selected 563 patients with acute wounds, documented in the WEC registry between 2007 and 2012. Wounds had existed for a median of 19 days (range 6-46 days). The majority of these were located on the leg (52%). Five significant independent predictors of prolonged wound healing were identified: wound location on the trunk [hazard ratio (HR) 0·565, 95% confidence interval (CI) 0·405-0·788; P = 0·001], wound infection (HR 0·728, 95% CI 0·534-0·991; P = 0·044), wound size (HR 0·993, 95% CI 0·988-0·997; P = 0·001), wound duration (HR 0·998, 95% CI 0·996-0·999; P = 0·005) and patient's age (HR 1·009, 95% CI 1·001-1·018; P = 0·020), but not diabetes. Awareness of the five factors predicting the healing of complex acute wounds, particularly wound infection and location on the trunk, may help caregivers to predict wound healing time and to detect, refer and focus on patients who need additional attention.

Extension of the right internal thoracic artery with the radial artery in extensive re-do coronary artery bypass grafting

BackgroundPatients with extensive coronary artery disease often require re-do coronary artery bypass grafting. However, autologous bypass material is sometimes sparse. Since long term patency of arterial graft material is superior to venous bypass grafting, we developed a technique to perform re-do total arterial coronary artery bypass grafting extending the right internal thoracic artery (RITA) with the radial artery (RA) in an end to end fashion to gain the needed length in patients with and without an open left thoracic artery (LITA).MethodsWe performed this approach in 27 consecutive patients (age: 67.93 ± 7.51 years). Data was analyzed retrospectively. 19 operations were first re-op, 6 were second re-op and two were third re-op procedures.ResultsCardiopulmonary bypass time was 115.42 minutes (±31.92 minutes) with one OPCAB procedure, and clamp time was 55.09 minutes (±22.41 minutes) excluding 10 procedures performed on beating heart. Bypass grafting included the RCA, Cx and LAD. An average of 1.96 anastomoses were performed in each patient. Complication rate was low with one intra-operative apoplexy and one prolonged wound healing after harvest of the radial artery. One patient needed long term pulmonary assist. There was no intra-operative or early postoperative death.ConclusionThe operational technique of elongation of the internal thoracic artery with the radial artery proved to be safe and feasible with acceptable operation times for a re-do procedure. We recommend this as an additional option to existing methods to perform a complete arterial revascularization mainly in patients with open left internal thoracic artery to LAD bypass.

New surgical modification of fascial closure following endovascular aortic pathology repair.

IntroductionThere are clear benefits of percutaneous versus open femoral access for endovascular aortic pathology repair. All closing devices commercially available are expensive. Surgical closure of the femoral artery risks potential prolonged wound healing and as a consequence longer hospital stay. Fascial closure is a technique that remains an interesting option.AimTo evaluate the efficacy of the surgical modification of hemostasis control after endovascular repair of aortic pathology.Material and methodsOne hundred sixteen common femoral arteries in a group of 58 patients underwent a minimally invasive procedure. Patients suffering from abdominal, thoracic aorta aneurysms, acute thoracic aorta type B dissections and traumatic aortic injury were treated.ResultsA 1-year period of experience in fascial closure of 116 common femoral arteries was presented in the group of 58 patients undergoing endovascular interventions. Five intraoperative complications were observed and one late. Three primary failures were due to hemorrhage in three arteries, one required open repair and two additional compression after the procedure. Two cases of limb ischemia required surgical correction of artery closure. One limb ischemia was detected 4 weeks later, and was treated conservatively. At 1 year, 92 fascial closures (80%) were in the follow-up and 24 (20%) were lost to follow-up.ConclusionsThis new modification of fascial closure is a safe and cheap method of arterial closure following endovascular repair of selected aortic pathologies. The usage of two suture lines makes this procedure easy and quick. Fascial closure technique is comparable to other techniques in terms of success and complication rates.