Systemic microvascular endothelial function with arteriovenous fistula creation in chronic kidney disease.

Background: This study aimed to determine changes in microvascular endothelial function with upper arm arteriovenous fistula (AVF) creation and maturation in patients with chronic kidney disease (CKD). Materials and Methods: This prospective cross-sectional study was performed at Hospital Universiti Sains Malaysia, a tertiary hospital in Malaysia. Forty CKD patients (stage 4-5) who were scheduled for elective AVF creation over the upper extremity for maintenance hemodialysis were recruited using convenience sampling method. Microvascular endothelial-dependent vasodilation was measured using laser Doppler flowmetry and the process of iontophoresis preoperatively and postoperatively at weeks 2 and 6. Fistula maturation was assessed at week 6. Results: Thirty-two patients had successful AVF maturation. Endothelial-dependent vasodilation (acetylcholine (Ach)% was higher (246.48 [standard deviation (SD) 209.38] vs. 104.95 [SD 43.29], P = 0.001) while systolic blood pressure was lower (142.25 [SD 21.50] vs. 162.25 [SD 13.26], P = 0.017) in this group as compared to unsuccessful AVF group. No significant changes were seen in overall microvascular endothelial-dependent vasodilation during the 6-week study period (day 0, 246.48 [SD 209.38]; week 2, 201.14 [SD 198.19]; and week 6, 203.53 [SD 145.89]). Conclusion: Upper arm AVF creation does not affect microvascular endothelial function up to 6 weeks post operation and may not contribute to the success of AVF maturation. However, the lower microvascular endothelial-dependent vasodilation and higher systolic blood pressure in unsuccessful AVF subjects need to be further studied.

Outcome of the Modified Meek Technique in the Management of Major Pediatric Burns.

INTRODUCTION: The modified Meek micrografting technique has been used in the treatment of severely burned patients and a number of articles have examined the use of the modified Meek technique in adults and in mixed-age groups. However, there is a paucity of research pertaining to the outcome in the pediatric age group. The aim of this study is to present our favorable outcome in pediatric major burns using the modified Meek technique. METHODS: A retrospective review of burn cases in Hospital Universiti Sains Malaysia from 2010 to 2015 was conducted. Cases of major burns among pediatric patients grafted using the Meek technique were examined. RESULTS: Twelve patients were grafted using the Meek technique. Ten (91.7%) patients were male, whereas 2 (8.3%) were female. The average age of patients was 6 years (range, 2-11 years). The average total body surface area was 35.4% (range, 15%-75%). Most burn mechanisms were due to flame injury (66.7%) as compared with scalds injury (16.7%) and chemical injury (16.7%). There was no mortality. All patients were completely grafted with a good donor site scar. The average graft take rate was 82.3%, although 8 cases had positive tissue cultures from the Meek-grafted areas. The average follow-up duration was 3.6 years (range, 1.1-6.7 years). Only 1 case developed contracture over minor joint. CONCLUSIONS: The Meek technique is useful when there is a paucity of donor site in the pediatric group. The graft take is good, contracture formation is low, and this technique is cost-effective.

Endothelium dependent hyperpolarization-type relaxation compensates for attenuated nitric oxide-mediated responses in subcutaneous arteries of diabetic patients.

Diabetes impairs endothelium-dependent relaxations. The present study evaluated the contribution of different endothelium-dependent relaxing mechanisms to the regulation of vascular tone in subcutaneous blood vessels of humans with Type 2 diabetes mellitus. Subcutaneous arteries were isolated from tissues of healthy controls and diabetics. Vascular function was determined using wire myography. Expressions of proteins were measured by Western blotting and immunostaining. Endothelium-dependent relaxations to acetylcholine were impaired in arteries from diabetics compared to controls (P = 0.009). Acetylcholine-induced nitric oxide (NO)-mediated relaxations [in the presence of an inhibitor of cyclooxygenases (COX; indomethacin) and small and intermediate conductance calcium-activated potassium channel blockers (UCL1684 and TRAM 34, respectively)] were attenuated in arteries from diabetics compared to controls (P < 0.001). However, endothelium-dependent hyperpolarization (EDH)-type relaxations [in the presence of indomethacin and the NO synthase blocker, l-NAME] were augmented in arteries from diabetics compared to controls (P = 0.003). Endothelium-independent relaxations to sodium nitroprusside (NO donor) and salbutamol (ß-adrenoceptor agonist) were preserved, but those to prostacyclin were attenuated in diabetics compared to controls (P = 0.017). In arteries of diabetics, protein expressions of endothelial NO synthase, prostacyclin synthase and prostacyclin receptors were decreased, but those of COX-2 were increased. These findings suggest that in human diabetes, the impairment of endothelium-dependent relaxations is caused by a diminished NO bioavailability; however, EDH appears to compensate, at least in part, for this dysfunction.

The Impact of Abdominoplasty vs Non-abdominoplasty on Weight Loss in Bariatric and Non-bariatric Malaysian Patients: A Multicentre Retrospective Study.

Background and aims Weight loss associated with abdominoplasty remains controversial as to whether it is contributed by the procedure alone, or if there are other patient factors. Therefore, we evaluated the relationship between weight loss in pre- and post-abdominoplasty and compared the weight loss of those who do not undergo abdominoplasty in bariatric and non-bariatric patients. Methods This study measured weight changes at designated time points in four different groups comprising 98 patients. The groups were abdominoplasty after bariatric surgery (group A), patients with abdominoplasty alone (B), bariatric surgery alone (group C), and diet alone (group D). Results are compared within and between the groups. Results Patients in groups A and B (patients who had abdominoplasty regardless with or without bariatric surgery) had a significant weight loss after six months (mean difference=10.70kg, 95% CI=4.05, 17.34, p<0.001) compared to pre abdominoplasty weight. Patients in group B were statistically significant (mean difference=4.01kg, 95% CI=0.92, 7.10, p=0.007) with 3.60kg weight reduction (4.59%). Patients in group A had clinically significant weight reduction (4.45kg, 5.14%) but it was not statistically significant (p>0.05) and had no significant additional weight reduction as compared to non-abdominoplasty (group C) patients (p=0.650). Patients in group C had a statistically significant difference from those in group D (F [1.00, 48.00] = 8.56, p=0.005) with an average weight loss of 3.60kg (4.59%) vs 2.56kg (2.8%) respectively. Conclusions All patients with abdominoplasty had significant weight loss after six months. Bariatric patients did not experience significant additional weight loss with abdominoplasty. Weight reduction after abdominoplasty alone was greater than diet alone.

Calcaneal Reconstruction With Free Deep Circumflex Iliac Artery Osseocutaneous Flap Following Aggressive Benign Bone Tumor Resection.

BACKGROUND: Advances in limb-salvage techniques have made total calcanectomy and primary reconstruction possible in managing calcaneal aggressive benign tumors and selected cases of intraosseous malignant tumors. However, there is still no consensus on the operative approach, oncologic margin, and the best reconstruction method to date. These 2 cases describe our experience in calcaneal reconstruction with the free deep circumflex iliac artery (DCIA) osseocutaneous flap in benign aggressive calcaneal tumors. METHODS: We reported 2 consecutive male and female patients, with an average age of 25 years (age 19 and 31, respectively), who underwent total calcanectomy and primary calcaneal reconstruction with the free DCIA osseocutaneous flaps for calcaneal chondroblastoma and giant cell tumor. A marginal resection of the entire calcaneus through the subtalar and calcaneocuboid joints (intra-articular approach) was performed in the first case and a wide local resection leaving 1 cm normal calcaneal bone margin anterosuperiorly (intraosseous approach) was performed in the second case. RESULTS: The follow-up period averaged 48 months. Negative oncologic margins were achieved in both cases. The first case was complicated with venous thrombosis; however, the graft remained viable after emergency reexploration. Normal foot function was restored with good solid osseous union and bony hypertrophy observed. Both patients achieved good short-term functional and aesthetic outcomes with no donor site pain or disability. No local recurrence was reported either. CONCLUSION: Primary calcaneal reconstruction with the free DCIA osseocutaneous flap can lead to good short-term functional and aesthetic outcomes. LEVEL OF EVIDENCE: Level IV, case series.

An unusual cause of subacute airway obstruction in a hemodialysis patient with brachio-cephalic arteriovenous fistula: A rare presentation of central venous occlusion.

A young lady with an arteriovenous (AV) fistula on hemodialysis was referred for surgical management following a failed endovascular approach to relieve central venous occlusion. She had an obstructed left brachiocephalic vein with a history of numerous central vein catheter placements. Alternative routes for new arteriovenous fistula creation had been exhausted due to previous contralateral upper limb fistula rupture and ligation. To the best of our knowledge, no similar cases of airway obstruction in central venous occlusion occurring in hemodialysis patients with AV fistula have been reported. The importance of identifying the possible emergency red flags in hemodialysis patients with central venous occlusion is important to prevent unwanted consequences.

The Practice of First Aid for Burn Injuries Among the Population of East Coast of Peninsular Malaysia for 2012-2016.

Burns are a devastating public health problem that result in 10 million disability-adjusted life-years lost in low- and middle-income countries. Adequate first aid for burn injuries reduces morbidity and mortality. The rate of proper first aid practices in other countries is 12% to 22%.1,2 A 5-year retrospective audit was performed on the database of the Burn Unit in Hospital Universiti Sains Malaysia for 2012-2016; this involved 485 patients from the east coast of Malaysia. The mean age of the patients is 17.3 years old. The audit on first aid practices for burn injury showed poor practice. Out of 485 burned patients, 261 patients (53.8%) claimed that they practiced first aid. However, only 24 out of 485 patients (5%) practiced the correct first aid technique where they run their burn wound under cool water for more than 20 minutes. Two hundred and twenty-two patients had not received any first aid. Two patients did not respond to the question on the first aid usage after burn injury. The mean age of patients who practiced first aid was 15.6 years old. Out of the 261 patients who practiced first aid, 167 (64%) run their wound under tap water for different durations. Others practiced traditional remedies such as the application of "Minyak Gamat" (6.5%), soy sauce (5.5%), other ointments (3.6%), milk (1.8%), and eggs (0.7%), as well as honey, butter, and cooking oil (0.4% each). First aid practices for burn injuries in the population of east coast Malaysia are still inadequate. The knowledge and awareness of school children and the general Malaysian population must be enhanced.

Blue rubber bleb nevus syndrome in a Malay girl: A case report and literature review.

INTRODUCTION: Blue Rubber Bleb Nevus Syndrome (BRBNS) also known as Bean's Syndrome is an atypical type of vascular malformation. To date, around 200 cases have been reported world-wide. In view of its low incidence rate, clinicians might misdiagnose and under treat. The key features of this syndrome are characterized by multiple cutaneous, soft tissue and gastrointestinal tract venous malformations. PRESENTATION OF CASE: We report the first case of Blue Rubber Bleb Nevus Syndrome in Malaysia, a 23 years old Malay girl who suffers from multiple cutaneous venous malformation and gastrointestinal bleeding episodes. DISCUSSION: The typical morbidity for this syndrome is symptomatic anemia due to secondary iron deficiency due to the gastrointestinal venous malformation bleeding. In managing the gastrointestinal bleeding, it mainly depends on the severity of gastrointestinal bleeding, some may resolve spontaneously, while the others may be needing blood transfusion, and some may require GIT resections. As for cutaneous lesions, normally it is innocuous depending on the region and size. Large or problematic cutaneous venous malformation might benefit from sclerotherapy or excision. CONCLUSION: Multidisciplinary approach is crucial in managing BRBNS case due to its complexity and the spectrum of multiple organ involvement to ensure the best outcome to the patient.

Microcalcification in the arterial wall and its relationship to the ultrasound criteria of maturation of the arteriovenous fistula.

INTRODUCTION:: A functioning and reliable arteriovenous fistula is a lifeline for individuals suffering from chronic kidney disease. The success and failure to arteriovenous fistula maturation have been frequently related to patient and surgeon factors. METHOD:: In total, 138 participants with stage IV and V chronic kidney disease were included in this prospective observational study. Preoperative vascular mapping using ultrasound was performed to evaluate the condition and size of the vessels to fulfil the inclusion criteria. Intraoperatively, the vessel size was measured prior to anastomosis under magnified view. A specimen from the arterial wall of 5 mm in diameter was obtained from the arterotomy for histopathology assessment. Arteriovenous maturation was assessed at 6 weeks with the guidance of the ultrasound criteria of rule of sixes. RESULTS:: From the total of 138 participants, 110 participants (79.7%) had matured arteriovenous fistula in 6 weeks. The mean size of the artery measured intraoperatively was 3.82 ± 1.33 mm and the vein was 4.05 ± 1.20 mm. Microcalcification in the arterial media which was hypothesised to be the cause of the arteriovenous fistula failure was insignificant, with a p value of 0.115. Despite having atherosclerosis in the artery, 83.3% of the arteriovenous fistula matured. CONCLUSION:: Microcalcification and atherosclerosis are frequently seen in the arteries of chronic kidney disease patients, but they do not explain arteriovenous fistula non-maturation.

A 20-year experience of immediate mandibular reconstruction using free fibula osteocutaneous flaps following ameloblastoma resection: Radical resection, outcomes, and recurrence.

BACKGROUND: The mandible is an important structure that is located in the lower third of the face. Large mandibular defects after tumor resection cause loss of its function. This study assessed the outcomes and tumor recurrence after immediate mandibular reconstruction using a free fibula osteocutaneous flap following radical resection of ameloblastoma. METHODS: This is a retrospective non-randomized study of outcomes and tumor recurrence of all patients diagnosed with mandibular ameloblastoma from August 1997 until August 2017 (20 years) requiring free fibula osteocutaneous flap reconstruction at a single institution. The patients were identified through an electronic operative database; subsequently, their medical records and photo documentation were retrieved. RESULTS: Twenty-seven patients were included in this study. Eighteen patients were male, while nine were female. The majority of the patients (48.1%) were in their third decade of life when they were diagnosed with ameloblastoma. All of them underwent radical resection of the tumor with a surgical margin of 2 cm (hemimandibulectomy in cases with a large tumor) and immediate mandibular reconstruction with a free fibula osteocutaneous flap. Two patients required revision of a vascular anastomosis due to venous thrombosis postoperatively, while one patient developed a flap recipient site infection. The flap success rate was 100%. There was no tumor recurrence during a mean follow-up period of 5.6 years. CONCLUSIONS: Mandibular ameloblastoma should be treated with segmental mandibulectomy (with a surgical margin of 2 cm) to reduce the risk of recurrence. Subsequent mandibular and adjacent soft tissue defects should be reconstructed immediately with a free fibula osteocutaneous flap.

Early outcomes of cleft and palatal width following anterior palate repair (vomerine flap) in infants with wide cleft lip and palate.

BACKGROUND: Anterior palatal repair performed during cleft lip repair using a vomerine flap may assist in recruiting additional soft tissue for subsequent completion of palatoplasty, especially in patients with a wide cleft. We present our early. RESULTS: in the hope of triggering a re-evaluation of this technique regarding its advantages for maxillary growth through further studies of patients with a wide cleft. METHODS: A retrospective analysis of patients with complete unilateral and bilateral cleft lip and palate was performed, including cleft and palatal measurements taken during initial surgery (lip repair together with anterior palate repair) and upon completion of palatoplasty. RESULTS: In total, 14 patients were included in this study, of whom nine (63.3%) had unilateral cleft lip and palate and five (37.5%) had bilateral cleft. All patients had a wide cleft palate. Lip and anterior palate repair was done at a median age of 3 months, while completion of palatoplasty was done at a median age of 10.5 months. Measurements taken upon completion of palatoplasty showed significant cleft width reduction in the mid-palate and intertubercle regions; however, the palatal arch distances at nearby landmarks showed non-significant marginal changes. CONCLUSIONS: Anterior palate repair using a vomerine flap significantly reduced the remaining cleft width, while the palatal width remained. Further research is warranted to explore the long-term effects of this technique in wide cleft patients in terms of facial growth.

Autogenous forearm loop arteriovenous fistula creation.

INTRODUCTION: Arteriovenous fistula is a lifeline for end-stage kidney disease patients on dialysis. The quality of the vein and artery to be used plays a crucial role in attaining a functioning, reliable and long-lasting arteriovenous fistula. The aim of the study is to present an alternative for haemodialysis access to preserve the upper arm vasculature for future use - the forearm loop arteriovenous fistula. METHODS: From October 2015 to September 2016, 202 patients with chronic kidney disease (CKD), stages 4 and 5, underwent arteriovenous fistula creation at the Universiti Sains Malaysia Hospital, Malaysia. Nine patients, with severe atherosclerosis of the distal artery, but with satisfactory veins, underwent forearm loop arteriovenous fistula creation. Maturation of the fistula was based on the classification by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI). RESULTS: All nine patients who underwent forearm loop arteriovenous fistula have had diabetes mellitus for more than 10 years. Only one fistula failed to mature within 6 weeks. Two arteriovenous fistulas thrombosed at 3 and 5 months, respectively, after the commencement of haemodialysis. However, the other six matured fistulas are still functioning well after a year of regular usage. CONCLUSIONS: Distal forearm arteries in diabetics may be severely atherosclerotic. Forearm loop arteriovenous fistula can be considered as the primary access for cases decided as inconvenient for fistula creation due to severe occlusive atherosclerotic disease of the forearm arteries; in order to preserve upper arm veins for future access procedures.

A prospective study evaluating wound healing with sea cucumber gel compared with hydrogel in treatment of skin graft donor sites.

BACKGROUND: Gamat (sea-cucumber) is a natural occurring fauna which is popularly used as traditional medication in Southeast Asian countries. There have been many animal studies done on its' biochemical properties and its' effects in vivo. The effect of gamat on human cutaneous wounds was studied using a split-skin graft donor site wound. METHODS: This was a comparative case-control study done on patients in Hospital Universiti Sains Malaysia (Hospital USM), requiring split-thickness skin grafting, whereby, the skin graft donor site was divided to almost equal halves, and applied with both gamat-based gel on one side, with Duoderm® hydrogel on the other side. The epithelialization of the wounds was observed and compared on days 10, 14 and 21. Pain score, and pruritus score were also observed. Repeated measure analysis of variance (ANOVA) test and Paired t-test was used to test statistical significance accordingly. RESULTS: No significant differences were seen in rates of epithelialization of wounds on days 10, 14 and 21 (p > 0.01). No significant difference was also seen in the pain score and pruritus score (p > 0.01). CONCLUSIONS: A gamat-based gel is comparable to conventional hydrogels in treatment of split-skin graft donor site. No adverse effects were observed in either group.

Mechanism Action of Platelets and Crucial Blood Coagulation Pathways in Hemostasis.

Blood is considered to be precious because it is the basic necessity for health; our body needs a steady provision of oxygen, supplied via blood, to reach billions of tissues and cells. Hematopoiesis is the process that generates blood cells of all lineages. However, platelets are the smallest blood component produced from the very large bone marrow cells called megakaryocytes and they play a fundamental role in thrombosis and hemostasis. Platelets contribute their hemostatic capacity via adhesion, activation and aggregation, which are triggered upon tissue injury, and these actions stimulate the coagulation factors and other mediators to achieve hemostasis. In addition, these coordinated series of events are the vital biological processes for wound healing phases. The aim of this review is to summarize and highlight the important pathways involved in achieving hemostasis that are ruled by platelets. In addition, this review also describes the mechanism action of platelets, including adhesion, activation, aggregation, and coagulation, as well as the factors that aid in hemostasis and wound healing.

Prognostic factors and survival rate of osteosarcoma: A single-institution study.

AIM: Osteosarcoma is a highly malignant primary bone tumor. The study aim to evaluate the prognostic factors influencing the survival rate in our center. METHODS: This was a retrospective cohort study of all patients treated between January 2005 and December 2010. RESULTS: We included 163 patients with an age range of 6-59 years (median = 19). The median follow-up was 47 months (range 36-84). The overall survival in patients who completed chemotherapy and surgery (n = 117) was 72% at 2 years and 44% at 5 years. Histologically, 99 (85%) had osteoblastic, 6 (5%) had chondroblastic and 3 (2.5%) had telangiectatic osteosarcoma. Limb salvage surgery was performed in 80 (49%) and 41 (25%) underwent amputation. However, 46 patients (28%) underwent no surgical intervention and incomplete chemotherapy. In total, 38/79 patients had a good chemotherapy response. There was a significantly better survival rate for limb salvage versus amputation. Independent prognostic factors for survival are compliance to treatment and presence of lung metastasis. CONCLUSION: The overall survival of osteosarcoma patients was influenced by the presence of pulmonary metastases and compliance to treatment. Histological subtype, different chemotherapy regimens and histological necrosis after chemotherapy did not significantly influence survival. The patients who did not complete treatment had significantly poorer survival.

Long-term outcome of free fibula osteocutaneous flap and massive allograft in the reconstruction of long bone defect.

Reconstruction of massive bone defects in bone tumors with allografts has been shown to have significant complications including infection, delayed or nonunion of allograft, and allograft fracture. Resection compounded with soft tissue defects requires skin coverage. A composite osteocutaneous free fibula offers an optimal solution where the allografts can be augmented mechanically and achieve biological incorporation. Following resection, the cutaneous component of the free osteocutaneous fibula flaps covers the massive soft tissue defect. In this retrospective study, the long-term outcome of 12 patients, who underwent single-stage limb reconstruction with massive allograft and free fibula osteocutaneous flaps instead of free fibula osteal flaps only, was evaluated. This study included 12 consecutive patients who had primary bone tumors and had follow-up for a minimum of 24 months. The mean age at the time of surgery was 19.8 years. A total of eight patients had primary malignant bone tumors (five osteosarcomas, two chondrosarcomas and one synovial sarcoma), and four patients had benign bone tumors (two giant-cell tumors, one aneurysmal bone cyst, and one neurofibromatosis). The mean follow-up for the 12 patients was 63 months (range 24-124 months). Out of the 10 patients, nine underwent lower-limb reconstruction and ambulated with partial weight bearing and full weight bearing at an average of 4.2 months and 8.2 months, respectively. In conclusion, augmentation of a massive allograft with free fibula osteocutaneous flap is an excellent alternative for reducing the long-term complication of massive allograft and concurrently addresses the soft tissue coverage.

Effect of the Novel Biodegradable N, O-Carboxymethylchitosan and Oligo-Chitosan on the Platelet Thrombogenicity Cascade in von Willebrand Disease.

INTRODUCTION: Von Willebrand disease (vWD) is the second least common hemostatic disorder in Malaysia, and it has a low prevalence. This study examined the underlying platelet thrombogenicity cascades in the presence of different formulations of chitosan-derivatives in vWD patients. This paper aimed to determine the significant influence of chitosan biomaterial in stimulating the platelet thrombogenicity cascades that involve the von Willebrand factor, Factor 8, Thromboxane A2, P2Y12 and Glycoprotein IIb/IIIa in vWD. MATERIALS AND METHODS: Variable chitosan formulations of N,O-Carboxymethylchitosan (NO-CMC) and Oligo-Chitosan (O-C) were tested. Fourteen vWD subjects voluntarily participated in this study after signing informed consent forms. The patient's demographic profiles, family history, type of vWD, clinical symptoms and laboratory profiles were recorded and analyzed. Enzyme-linked immunosorbent assay, flow cytometry and Western blot tests were used to determine the level of the chitosan-adhered-platelet-mechanisms. RESULTS: The study revealed that most patients were predominantly affected by vWD type I. The O-C group of chitosan's scaffold pores is sufficient to allow for nutrients and cells. The O-C-stimulated-mediators are capable of initiating the platelet actions and were detected to expedite the blood coagulation processes. The oligo-group of chitosans was capable of amplifying and triggering more platelet activator's pathways via the studied mediators. The present findings suggest that the ability of each type of chitosan to coagulate blood varies depending on its chemical composition. CONCLUSION: The oligo group of chitosans is potentially capable of triggering platelet thrombogenicity cascades by activating platelets in vWD patients to form a platelet plug for hemostasis process.

Wound bed preparation for chronic diabetic foot ulcers.

The escalating incidence of diabetic mellitus has given rise to the increasing problems of chronic diabetic ulcers that confront the practice of medicine. Peripheral vascular disease, neuropathy, and infection contribute to the multifactorial pathogenesis of diabetic ulcers. Approaches to the management of diabetic ulcers should start with an assessment and optimization of the patient's general conditions, followed by considerations of the local and regional factors. This paper aims to address the management strategies for wound bed preparation in chronic diabetic foot ulcers and also emphasizes the importance of preventive measures and future directions. The "TIME" framework in wound bed preparation encompasses tissue management, inflammation and infection control, moisture balance, and epithelial (edge) advancement. Tissue management aims to remove the necrotic tissue burden via various methods of debridement. Infection and inflammation control restores bacterial balance with the reduction of bacterial biofilms. Achieving a moist wound healing environment without excessive wound moisture or dryness will result in moisture balance. Epithelial advancement is promoted via removing the physical and biochemical barriers for migration of epithelium from wound edges. These systematic and holistic approaches will potentiate the healing abilities of the chronic diabetic ulcers, including those that are recalcitrant.