Comparative study of two series of distally based fasciocutaneous flaps for coverage of the lower one-fourth of the leg, the ankle, and the foot

Skin defects over the lower one-fourth of the leg and over the foot are difficult to cover. Two types of pedicled fasciocutaneous flaps used to cover such defects were studied: the lateral supramalleolar flap and the distally based sural neurocutaneous flap. The series consisted of 27 and 36 cases, respectively. The lateral supramalleolar flap was used 27 times: for skin defects over the ankle (4), foot (16), and leg (7). The distally based sural neurocutaneous flap was used 42 times: over the foot (24), ankle (13), and leg (5). Fourteen of these patients were 65 years of age or older, and local vascularity was diminished in 16 cases. The flaps were evaluated clinically twice: in the immediate postoperative period for survival or for partial or total flap necrosis, and again to determine the presence of pain at the donor or recipient sites and the cosmetic appearance. Thirty-nine patients (62 percent) were reviewed subsequently, with a mean follow-up of 5 years for the supramalleolar flap and 2 years for the sural neurocutaneous flap. The results were evaluated for the presence or absence of pain, the appearance of the flap, the disability due to the insensate nature of the flap, and the presence or absence of secondary ulceration. Painful neuromata were noted in three cases with the sural neurocutaneous flap, whereas complete necrosis of the supramalleolar artery flap occurred in three patients. The distally based sural neurocutaneous island flap is very reliable, even in debilitated patients. Though the lateral supramalleolar artery flap offers the possibility of covering the same areas as the sural neurocutaneous flap, it is much less reliable in the presence of diminished local vascularity (18.5 percent failure rate as compared with 4.8 percent for the sural neurocutaneous flap). Because the procedure can cover extensive defects and is easy to perform, the distally based sural neurocutaneous flap was the method of choice for covering skin defects over the foot, heel, ankle, and the lower one-fourth of the leg. The lateral supramalleolar artery flap is indicated only when the sural neurocutaneous flap is contraindicated.     

One-stage reconstruction of composite bone and soft-tissue defects in traumatic lower extremities

Management of bone loss that occurs after severe trauma of open lower extremity fractures continues to challenge reconstructive surgeons. Sixty-one patients who had 62 traumatic open lower extremity fractures and combined bone and composite soft-tissue defects were treated with the following protocol: extensive debridement of necrotic tissues, eradication of infection, and vascularization of osteocutaneous tissue for one-stage bone and soft-tissue coverage reconstruction. The mechanism of injury included 49 motorcycle accidents (80.3 percent), five falls (8.2 percent), three crush injuries (4.9 percent), two pedestrian-automobile accidents (3.3 percent), and two motor vehicle accidents (3.3 percent). The bone defects were located in the tibia in 49 patients (79 percent; one patient had bilateral open tibial fractures), in the femur in seven patients (11.3 percent), in the calcaneus bone in four patients (6.5 percent), and in the metatarsal bones in two patients (3.2 percent). The size of soft-tissue defects ranged from 5 x 9 cm to 30 x 17 cm. The average length of the preoperative bony defect was 11.7 cm. The average duration from injury to one-stage reconstruction was 27.1 days, and the average number of previous extensive debridement procedures was 3.4. Fifty patients had vascularized fibula osteoseptocutaneous flaps, six had vascularized iliac osteocutaneous flaps, and five patients had seven combined vascularized rib transfers with serratus anterior muscle and/or latissimus dorsi muscle transfers. One patient received a second combined rib flap because the first combined rib flap failed. The rate of complete flap survival was 88.9 percent (56 of 63 flaps). Two combined vascularized rib transfers with serratus anterior muscle and latissimus dorsi muscle flaps were lost totally (3.2 percent) because of arterial thrombosis and deep infection, respectively. Partial skin flap losses were encountered in the five fibula osteoseptocutaneous flaps (7.9 percent). Postoperative infection for this one-stage reconstruction was 7.9 percent. Excluding the failed flap and the infected/amputated limb, the primary bony union rate after successful free vascularized bone grafting was 88.5 percent (54 of 61 transfers). The average primary union time was 6.9 months. The overall union rate was 96.7 percent (59 of 61 transfers). The average time to overall union was 8.5 months after surgery. Seven transferred vascularized bones had stress fractures, for a rate of 11.5 percent. Donor-site problems were noted in six fibular flaps, in two iliac flaps, and in one rib flap. The fibular donor-site problems were foot drop in one patient, superficial peroneal nerve palsy in one patient, contracture of the flexor hallucis longus muscle in two patients, and skin necrosis after split-thickness skin grafting in two patients. The iliac flap donor-site problems were temporary flank pain in one patient and lateral thigh numbness in the other. One rib flap transfer patient had pleural fibrosis. Transfer of the appropriate combination of vascularized bone and soft-tissue flap with a one-stage procedure provides complex lower extremity defects with successful functional results that are almost equal to the previously reported microsurgical staged procedures and conventional techniques.     

Cardiac effects of burn injury complicated by aspiration pneumonia-induced sepsis

Early fluid resuscitation, antimicrobials, early excision, and grafting have improved survival in the early postburn period; however, a significant incidence of pneumonia-related sepsis occurs after burn injury, often progressing to multiple organ failure. Recent studies have suggested that this initial injury (burn injury) primes the subject, producing an exaggerated response to a second insult, such as pneumonia-related sepsis. We developed an experimental animal model that included a third-degree burn over 40% of the total body surface area, followed by sepsis (intratracheal administration of Streptococcus pneumoniae, 4 x 106 colony-forming unit), which was produced either 48 or 72 h after burn injury in adult male rats. Hearts harvested after either burn alone, sepsis alone, or burn plus sepsis were used to assess either contractile function (Langendorff) or cardiomyocyte secretion of tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL-10 (ELISA). Experimental groups included the following: 1). sham (sham burn and no sepsis); 2). burn injury alone studied either 24, 48, or 72 h postburn; 3). pneumonia-related sepsis in the absence of burn injury; and 4). pneumonia-induced sepsis studied either 48 or 72 h after an initial burn injury. Burn injury alone (24 h) or sepsis alone produced myocardial contractile defects and increases in pro- and anti-inflammatory cytokine secretion by cardiomyocytes. Sepsis that occurred 48 h postburn exacerbated the cardiac contractile defects seen with either burn alone or sepsis alone. Sepsis that occurred 72 h postburn produced contractile defects resembling those seen in either burn alone or sepsis alone. In conclusion, our data suggest that burn injury primes the subject such that a second insult early in the postburn period produces significantly greater cardiac abnormalities than those seen with either burn alone or sepsis alone.     

Tumor necrosis factor-α synthesis inhibitor, 3,6'-dithiothalidomide, reverses behavioral impairments induced by minimal traumatic brain injury in mice

Mild traumatic brain injury (mTBI) patients do not show clear structural brain defects and, in general, do not require hospitalization, but frequently suffer from long-lasting cognitive, behavioral and emotional difficulties. Although there is no current effective treatment or cure for mTBI, tumor necrosis factor-alpha (TNF-α), a cytokine fundamental in the systemic inflammatory process, represents a potential drug target. TNF-α levels increase after mTBI and may induce or exacerbate secondary damage to brain tissue. The present study evaluated the efficacy of the experimental TNF-α synthesis inhibitor, 3,6'-dithiothalidomide, on recovery of mice from mTBI in a closed head weight-drop model that induces an acute elevation in brain TNF-α and an impairment in cognitive performance, as assessed by the Y-maze, by novel object recognition and by passive avoidance paradigms at 72 h and 7 days after injury. These impairments were fully ameliorated in mice that received a one time administration of 3,6'-dithiothalidomide at either a low (28 mg/kg) or high (56 mg/kg) dose provided either 1 h prior to injury, or at 1 or 12 h post-injury. Together, these results implicate TNF-α as a drug target for mTBI and suggests that 3,6'-dithiothalidomide may act as a neuroprotective drug to minimize impairment.     

The role of intrinsic muscle flaps of the foot for bone coverage in foot and ankle defects in diabetic and nondiabetic patients

Local muscle flaps, pioneered by Ger in the late 1960s, were extensively used for foot and ankle reconstruction until the late 1970s when, with the evolution of microsurgery, microsurgical free flaps became the reconstructive method of choice. To assess whether the current underuse of local muscle flaps in foot and ankle surgery is justified, the authors identified from the Georgetown Limb Salvage Registry all patients who underwent foot and ankle reconstruction with local muscle flaps and microsurgical free flaps from 1990 through 1998. By protocol, flap coverage was the reconstructive choice for defects with exposed tendons, joints, or bone. Local muscle flaps were selected over free flaps if the defect was small (3 x 6 cm or less) and within reach of the local muscle flap. During the same time frame, the authors performed 45 free flaps (96 percent success rate) in the same areas when the defects were too large or out of reach of local muscle flaps. Thirty-two consecutive patients underwent local muscle flap reconstruction for 19 diabetic wounds and 13 traumatic wounds. All wounds, after debridement, had exposed bone at their base, with osteomyelitis being present in 52 percent of the diabetic wounds and in 70 percent of the nondiabetic wounds. Wounds were located in the hindfoot (47 percent), midfoot (44 percent), and ankle (9 percent). Vascular disease was more prevalent in the diabetic group, in which 42 percent of the affected limbs required revascularization procedures before reconstruction (versus 7 percent in the nondiabetic group). Subsequently, 83 total operations were required to heal the wounds, of which 46 percent were limited to debridement only. Thirty-four pedicled muscle flaps were used: 19 abductor digiti minimi (56 percent), nine abductor hallucis (26 percent), three extensor digitorum brevis (9 percent), two flexor digitorum brevis (6 percent), and one flexor digiti minimi (3 percent). An additional skin graft for complete coverage was required in 18 patients (53 percent). One patient died and one flap developed distal necrosis, for a 96 percent success rate. The complication rate was 26 percent and included patient death, dehiscence, and partial flap or split-thickness skin graft loss. Twenty-nine of the 32 wounds healed. One patient died in the postoperative period; in two others the wounds failed to heal and required below-knee amputations, for an overall limb salvage rate of 91 percent. Diabetes did not significantly affect healing and limb salvage rates. Diabetes, however, did affect healing times (twofold increase), length of stay (2.7 times as long), and long-term survival (63 percent survival in diabetic patients versus 100 percent in the trauma group). Local muscle flaps provide a simpler, less expensive, and successful alternative to microsurgical free flaps for foot and ankle defects that have exposed bone (with or without osteomyelitis), tendon, or joint at their base. Diabetes does not appear to adversely affect the effectiveness of these flaps. Local muscle flaps should remain on the forefront of possible reconstructive options when treating small foot and ankle wounds that have exposed bone, tendon, or joint.     

Spinal cord injury causes sustained disruption of the blood-testis barrier in the rat

There is a high incidence of infertility in males following traumatic spinal cord injury (SCI). Quality of semen is frequently poor in these patients, but the pathophysiological mechanism(s) causing this are not known. Blood-testis barrier (BTB) integrity following SCI has not previously been examined. The objective of this study was to characterize the effects of spinal contusion injury on the BTB in the rat. 63 adult, male Sprague Dawley rats received SCI (n = 28), laminectomy only (n = 7) or served as uninjured, age-matched controls (n = 28). Using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), BTB permeability to the vascular contrast agent gadopentate dimeglumine (Gd) was assessed at either 72 hours-, or 10 months post-SCI. DCE-MRI data revealed that BTB permeability to Gd was greater than controls at both 72 h and 10 mo post-SCI. Histological evaluation of testis tissue showed increased BTB permeability to immunoglobulin G at both 72 hours- and 10 months post-SCI, compared to age-matched sham-operated and uninjured controls. Tight junctional integrity within the seminiferous epithelium was assessed; at 72 hours post-SCI, decreased expression of the tight junction protein occludin was observed. Presence of inflammation in the testes was also examined. High expression of the proinflammatory cytokine interleukin-1 beta was detected in testis tissue. CD68⁺ immune cell infiltrate and mast cells were also detected within the seminiferous epithelium of both acute and chronic SCI groups but not in controls. In addition, extensive germ cell apoptosis was observed at 72 h post-SCI. Based on these results, we conclude that SCI is followed by compromised BTB integrity by as early as 72 hours post-injury in rats and is accompanied by a substantial immune response within the testis. Furthermore, our results indicate that the BTB remains compromised and testis immune cell infiltration persists for months after the initial injury.     

带腓肠腱膜的腓肠神经营养皮瓣修复KuwadeⅣ型跟腱缺损

目的:回顾性分析带腓肠肌腱膜的腓肠神经营养皮瓣修复KuwadeⅣ型跟腱缺损的临床病例,探讨其手术注意事项及治疗经验。方法:总结2008年5月-2013年8月收治的KuwadeⅣ型跟腱缺损19例,应用带腓肠肌腱膜的腓肠神经营养皮瓣进行一期修复。7例为新鲜损伤,12例为陈旧性缺损。19例跟腱缺损均伴有皮肤及软组织坏死,皮肤缺损范围为4.0 cm×6.0 cm-6.0cm×12.0 cm,跟腱缺损长度为5-9 cm,术中皮瓣切取范围为6.0 cm×5.5 cm-12.0 cm×8.0cm,腓肠腱膜切取范围5.5 cm×6.0cm-10.0 cm×6.0 cm;供区游离植皮修复。客观性评价指标包括关节跖屈、背伸动度及形态学,主观性评价采用AOFAS评分。结果:术后17例跟腱功能重建良好,2例感染控制不良,跟腱移植体部分坏死。皮瓣完全成活13例,创面Ⅰ期愈合。2例术后6天皮瓣远端表皮坏死,经换药后愈合。2例术后10天皮瓣远端部分坏死,经局部皮瓣移位修复愈合,2例感染控制不良者,皮瓣未愈合,移植跟腱部分坏死,经再次清创后,行阔筋膜条修复术,局部皮瓣移位修复。术后19例均获随访,随访时间6~24个月,平均18个月。术后皮瓣略臃肿,但不影响穿鞋,行走功能恢复良好,术后1年AOFAS评分平均80.31分。结论:带腓肠肌腱膜的腓肠神经营养皮瓣用于治疗KuwadeⅣ型跟腱缺损,可以同时修复皮肤及跟腱缺损,是一种较为理想的一期修复方法。     

The groin flap in reparative surgery of the hand

The historical literature of the use of axial vascular pattern flaps from the hypogastric and iliofemoral regions in reparative surgery of the hand is concisely reviewed. Thirty-six iliofemoral (groin) flaps were utilized for delayed primary resurfacing and secondary reconstruction of defects of the hand and forearm. Two flaps (6 percent) were complicated by partial necrosis. We caution against the immediate resurfacing (within 24 hours of injury) of acute crushed hand wounds by distant flaps. The immediate application of a healthy flap on a soiled or crushed wound invites complications of local tissue necrosis, infection, and subsequent loss of the flap. When distant flaps are indicated for coverage of acute hand wounds, delayed primary coverage following complete removal of all nonviable tissue is a safe and reliable regimen. It is advantageous to design the serviceable portion of the flap on the distal area of the vascular territory of the groin flap. Thoughtful yet "radical" defatting can be performed on the lateral portion of the groin flap territory. Constructed in this way, the long medial base of the groin flap allows freedom for movement at the wrist and metacarpophalangeal and interphalangeal joints, thus decreasing edema and stiffness. In the management of soft-tissue defects in the hand requiring distant flap coverage, we choose to utilize the conventional groin flap in preference to the microvascular free flap when both techniques will deliver equal results.     

重症五步蛇咬伤深筋膜室网状切开的早期应用

目的探讨重症五步蛇伤患者行深筋膜室网状切开的早期应用。方法选择2007年4月～2011年12月我院收治被五步蛇咬伤后3h内就诊,且患肢组织压在25mmHg以上的患者44例,其中行深筋膜室网状切开13例作为研究组（A组）,使用传统保守非手术治疗31例作为对照组（B组）,观察两组患者72h内组织压的变化、肿胀程度的改变、创口出血及坏死情况,并进行比较。结果两组比较,A组24h后组织压基本降至正常,肿胀程度比B组轻;A组患者伤口有明显出血渗血,早期B组优于A组,但3h后两组的出血情况对比无明显差异。A组2例患者伤处有片状坏死;B组绝大部分患者72h后经切除坏死组织后肿胀明显消退,1例患者因骨筋膜室综合征导致截肢,两组对比有显著统计学差异。结论在重症五步蛇伤中,审慎深筋膜室网状切开患肢,可避免组织坏死、骨筋膜室综合征形成及大出血的发生。     

Bicycle spoke injuries in the lower extremity

This study reports the authors' 5-year experience with treating lower extremity injuries in bicycle passengers caused by the spokes. This patient group was selected from 716 lower extremity injuries that received treatment at our outpatient plastic surgery clinic. A total of 26 patients were treated during the study. Patients ranged from 2 to 19 years old, with a mean age of 5.6 years. The authors treated more female passengers (62 percent) than male passengers. The right foot (52 percent) was involved more often than was the left. Most patients were injured in the afternoon, from 2 to 7 PM (62 percent), and between May and October (77 percent). The rear wheel (89 percent) injured the majority of patients. The Achilles tendon was the most common site of injury (63 percent). The typical types of wounds observed included the following: type I, laceration with partial avulsion of skin and subcutaneous tissue (41 percent) and laceration forming a distally based flap (33 percent); type II, abrasions with ecchymoses and friction burn from the shearing effect of the spokes creating a partial- to full-thickness skin defect (26 percent). Of the type I injuries, full-thickness skin lacerations (33 percent) were closed primarily. Partial-thickness skin lacerations, abrasions, ecchymoses, and skin defects (67 percent) were treated conservatively with wound irrigation and dressing. The wound healing time for type I injuries was 29 days; for type II injuries, it was 27 days. These healing times were prolonged compared with healing by first intention. No significant difference was found in healing time when comparing both types of injury. Four patients required hospitalization. No patient required skin grafting. No fractures were noted because these patients were selected from the outpatient plastic surgery clinic and did not include patients from the emergency room. Since the first report of bicycle spoke injuries a half-century ago, prevention has not improved.     

Evaluation of fasciotomy and vasodilator for treatment of frostbite in the dog

Severe freezing injury was produced in the hind foot of 26 mongrel dogs. All dogs were given daily whirlpool treatment and protective bandaging for 14 days following injury. In addition, certain dogs received a vasodilator, fasciotomy, or both vasodilator and fasciotomy following injury. Deep foot temperatures, foot volumes, tissue pressures, and 14 day tissue loss-salvage scores were compared. Significant differences between fasciotomy and nonfasciotomy dogs were seen in foot temperature, volume, and tissue pressure immediately following fasciotomy. Though there was no significant difference in 14 day tissue loss, there was clinically apparent prolongation of integrity of the local vascular system for 2 to 5 days following fasciotomy, and total foot salvage in several dogs receiving fasciotomy.     

The concept of fillet flaps: classification, indications, and analysis of their clinical value

Tissue of amputated or nonsalvageable limbs may be used for reconstruction of complex defects resulting from tumor and trauma. This is the "spare parts" concept.By definition, fillet flaps are axial-pattern flaps that can function as composite-tissue transfers. They can be used as pedicled or free flaps and are a beneficial reconstruction strategy for major defects, provided there is tissue available adjacent to these defects.From 1988 to 1999, 104 fillet flap procedures were performed on 94 patients (50 pedicled finger and toe fillets, 36 pedicled limb fillets, and 18 free microsurgical fillet flaps).Nineteen pedicled finger fillets were used for defects of the dorsum or volar aspect of the hand, and 14 digital defects and 11 defects of the forefoot were covered with pedicled fillets from adjacent toes and fingers. The average size of the defects was 23 cm2. Fourteen fingers were salvaged. Eleven ray amputations, two extended procedures for coverage of the hand, and nine forefoot amputations were prevented. In four cases, a partial or total necrosis of a fillet flap occurred (one patient with diabetic vascular disease, one with Dupuytren's contracture, and two with high-voltage electrical injuries).Thirty-six pedicled limb fillet flaps were used in 35 cases. In 12 cases, salvage of above-knee or below-knee amputated stumps was achieved with a plantar neurovascular island pedicled flap. In seven other cases, sacral, pelvic, groin, hip, abdominal wall, or lumbar defects were reconstructed with fillet-of-thigh or entire-limb fillet flaps. In five cases, defects of shoulder, head, neck, and thoracic wall were covered with upper-arm fillet flaps. In nine cases, defects of the forefoot were covered by adjacent dorsal or plantar fillet flaps. In two other cases, defects of the upper arm or the proximal forearm were reconstructed with a forearm fillet. The average size of these defects was 512 cm2. Thirteen major joints were salvaged, three stumps were lengthened, and nine foot or forefoot amputations were prevented. One partial flap necrosis occurred in a patient with a fillet-of-sole flap. In another case, wound infection required revision and above-knee amputation with removal of the flap.Nine free plantar fillet flaps were performed-five for coverage of amputation stumps and four for sacral pressure sores. Seven free forearm fillet flaps, one free flap of forearm and hand, and one forearm and distal upper-arm fillet flap were performed for defect coverage of the shoulder and neck area. The average size of these defects was 432 cm2. Four knee joints were salvaged and one above-knee stump was lengthened. No flap necrosis was observed. One patient died of acute respiratory distress syndrome 6 days after surgery.Major complications were predominantly encountered in small finger and toe fillet flaps. Overall complication rate, including wound dehiscence and secondary grafting, was 18 percent. This complication rate seems acceptable. Major complications such as flap loss, flap revision, or severe infection occurred in only 7.5 percent of cases. The majority of our cases resulted from severe trauma with infected and necrotic soft tissues, disseminated tumor disease, or ulcers in elderly, multimorbid patients.On the basis of these data, a classification was developed that facilitates multicenter comparison of procedures and their clinical success. Fillet flaps facilitate reconstruction in difficult and complex cases. The spare part concept should be integrated into each trauma algorithm to avoid additional donor-site morbidity and facilitate stump-length preservation or limb salvage.     

Reconstruction of large sacral defects following total sacrectomy

Total sacrectomies for cancer ablation often result in extensive defects that are challenging to reconstruct. In an effort to elucidate the criteria to select the most effective reconstructive options, we reviewed our experience with the management of large sacral wound defects. All patients who had a sacral defect reconstruction after a total sacrectomy at our institution between January of 1993 and August of 1998 were reviewed. The size of the defect, the type of reconstruction, postoperative complications, and functional outcome in each patient were assessed. A total of 27 flaps were performed in 25 patients for sacral defect reconstruction after a total sacrectomy. Diagnoses consisted of chordoma (n = 13), giant cell carcinoma (n = 2), sarcoma (n = 5), rectal adenocarcinoma (n = 4), and radiation induced necrosis (n = 1). The size of sacral defects ranged from 18 to 450 cm2 (mean, 189.8 cm2). Ten patients, including five who had preoperative radiation therapy, underwent transpelvic vertical rectus abdominis myocutaneous (VRAM) flap reconstruction for sacral defects with a mean size of 203.3 cm2. Of these, five patients (50 percent) had complications (four minor wound dehiscences and one seroma). Eight patients, including one who had preoperative radiation therapy, underwent bilateral gluteal advancement flap reconstruction for sacral defects with a mean size of 198.0 cm2. They had no complications. Two patients, both of whom had preoperative radiation therapy, underwent gluteal rotation flap reconstruction for sacral defects of 120 cm2 and 144 cm2. Both patients had complications (one partial flap loss and one nonhealing wound requiring a free flap). Three patients, including one who had preoperative radiation therapy, underwent reconstruction with combined gluteal and posterior thigh flaps for sacral defects with a mean size of 246 cm2; two of these patients had partial necrosis of the posterior thigh flaps. Three patients, all of whom had preoperative radiation therapy, underwent free flap reconstruction for sacral defects with a mean size of 144.3 cm2. They had no complications. Our experience suggests that there are three reliable options for the reconstruction of large sacral wound defects: bilateral gluteal advancement flaps, transpelvic rectus myocutaneous flaps, and free flaps. In patients with no preoperative radiation therapy and intact gluteal vessels, the use of bilateral gluteal advancement flaps should be considered. In patients with a history of radiation to the sacral area and in patients whose gluteal vessels have been damaged, the use of the transpelvic VRAM flap should be considered. If the transpelvic VRAM flap cannot be used because of previous abdominal surgery, a free flap should be considered as a last option.     

Mechanism of action, development and clinical experience of recombinant FVIIa

Recombinant FVIIa has been developed for treatment of bleedings in hemophilia patients with inhibitors, and has been found to induce hemostasis even during major surgery such as major orthopedic surgery. Recombinant FVIIa is being produced in BHK cell cultures and has been shown to be very similar to plasma-derived FVIIa. The use of rFVIIa in hemophilia treatment is a new concept of treatment and is based on the low affinity binding of FVIIa to the surface of thrombin activated platelets demonstrated in a cell-based in vitro model. By the administration of pharmacological doses of exogenous rFVIIa the thrombin generation on the platelet surface at the site of injury is enhanced independently of the presence of FVIII/FIX. As a result of the increased and rapid thrombin formation, a tight fibrin hemostatic plug is being formed. A tight fibrin structure has been found to be more resistant to fibrinolytic degradation thereby helping to maintain hemostasis. The general mechanism of action of pharmacological doses of rFVIIa shown to induce hemostasis not only in hemophilia, but also in patients with platelet defects, and with profuse bleedings triggered by extensive surgery or trauma, may very well be the capacity of generating a tight fibrin hemostatic plug through the increased thrombin generation. Such a fibrin plug will help to resist the overwhelming mostly local release of fibrinolytic activity triggered by the vast tissue damage occurring in extensive trauma. A release of fibrinlytic activity locally has also been demonstrated to occur in the gastrointestinal tract as well as during profuse postpartum bleedings. Pharmacological doses of rFVIIa have in fact, also been shown to induce hemostasis in such cases.     

Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration

Renal ischaemia reperfusion injury (IRI) is a common cause of acute kidney injury (AKI) in patients and occlusion of renal blood flow is unavoidable during renal transplantation. Experimental models that accurately and reproducibly recapitulate renal IRI are crucial in dissecting the pathophysiology of AKI and the development of novel therapeutic agents. Presented here is a mouse model of renal IRI that results in reproducible AKI. This is achieved by a midline laparotomy approach for the surgery with one incision allowing both a right nephrectomy that provides control tissue and clamping of the left renal pedicle to induce ischaemia of the left kidney. By careful monitoring of the clamp position and body temperature during the period of ischaemia this model achieves reproducible functional and structural injury. Mice sacrificed 24 hr following surgery demonstrate loss of renal function with elevation of the serum or plasma creatinine level as well as structural kidney damage with acute tubular necrosis evident. Renal function improves and the acute tissue injury resolves during the course of 7 days following renal IRI such that this model may be used to study renal regeneration. This model of renal IRI has been utilized to study the molecular and cellular pathophysiology of AKI as well as analysis of the subsequent renal regeneration.     

Forefoot reconstruction by reversed island flaps in diabetic patients

Soft-tissue coverage of the foot is often difficult, especially when the distal third of the foot (dorsal or plantar aspects) is involved. The clinical situation can be further complicated when diabetic patients are affected by painful and unstable wounds of this kind because of the familiar phenomenon of vasculopathy. The purpose of this study was to evaluate the possibility of using distally based foot flaps to cover forefoot defects in diabetic patients. Preoperative selection of patients was the key to this study; those who had other major disease, chronic infection, bone involvement, and/or insufficient foot vascularization were excluded from the study. The authors report a series of 12 diabetic patients in whom the reconstruction of medium-sized defects (ranging from 1.5 x 2.0 cm to 3.0 x 7.0 cm) of the forefoot was performed using distally based dorsalis pedis flaps or medial plantar flaps. The transferred flaps survived and adapted well to the defects, except for one flap in a patient who had a slight venous insufficiency at outset. Wearing their own footwear, patients could walk after 20 to 30 days. After the follow-up period (3 months to 3 years), no skin breakdown in the treated areas was observed. Temporary donor-site pain was reported by medial plantar flap patients, and partial skin graft loss at the donor site occurred in some of the dorsalis pedis patients. The authors suggest that in selected cases, medium-sized soft-tissue defects involving the dorsal aspects or the weight-bearing areas of the diabetic foot can be successfully covered with distally based island flaps.     

Free microvascular muscle flaps with skin graft reconstruction of extensive defects of the foot: a clinical and gait analysis study

Over the past 4 years at the Massachusetts General Hospital 18 patients have been treated for extensive defects (mean size 130 cm2) of the foot at or below the medial and lateral malleoli. These patients have been treated with free muscle flaps covered with thick split-thickness skin grafts. Full muscle flap survival has been seen in each patient, and all patients are currently ambulatory. A subgroup of nine patients are weight-bearing directly upon their skin grafts covering transferred muscle. All patients are walking without chronic breakdown over a mean follow-up of over 19 months with the exception of a single patient who has had breakdown in a region of redundant improperly tailored muscle flap. None of the skin grafted muscles has significant cutaneous sensibility. Detailed gait analysis of these patients has confirmed the weight-bearing capabilities of free muscle flaps with skin grafts and has proven to be an excellent method of foot reconstruction evaluation. It would appear from this study that cutaneous sensibility may not be necessary for successful reconstruction of the weight-bearing surface of the foot. This method of reconstruction should be considered when local tissues are not suitable for plantar foot reconstruction.     

Mild electrical stimulation and heat shock ameliorates progressive proteinuria and renal inflammation in mouse model of alport syndrome

Alport syndrome is a hereditary glomerulopathy with proteinuria and nephritis caused by defects in genes encoding type IV collagen in the glomerular basement membrane. All male and most female patients develop end-stage renal disease. Effective treatment to stop or decelerate the progression of proteinuria and nephritis is still under investigation. Here we showed that combination treatment of mild electrical stress (MES) and heat stress (HS) ameliorated progressive proteinuria and renal injury in mouse model of Alport syndrome. The expressions of kidney injury marker neutrophil gelatinase-associated lipocalin and pro-inflammatory cytokines interleukin-6, tumor necrosis factor-α and interleukin-1β were suppressed by MES+HS treatment. The anti-proteinuric effect of MES+HS treatment is mediated by podocytic activation of phosphatidylinositol 3-OH kinase (PI3K)-Akt and heat shock protein 72 (Hsp72)-dependent pathways in vitro and in vivo. The anti-inflammatory effect of MES+HS was mediated by glomerular activation of c-jun NH(2)-terminal kinase 1/2 (JNK1/2) and p38-dependent pathways ex vivo. Collectively, our studies show that combination treatment of MES and HS confers anti-proteinuric and anti-inflammatory effects on Alport mice likely through the activation of multiple signaling pathways including PI3K-Akt, Hsp72, JNK1/2, and p38 pathways, providing a novel candidate therapeutic strategy to decelerate the progression of patho-phenotypes in Alport syndrome.     

Hypotheses, rationale, design, and methods for prognostic evaluation of cardiac biomarker elevation after percutaneous and surgical revascularization in the absence of manifest myocardial infarction. A comparative analysis of biomarkers and cardiac magnetic resonance. The MASS-V Trial

ABSTRACT: BACKGROUND: Although the release of cardiac biomarkers after percutaneous (PCI) or surgical revascularization (CABG) is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR) consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. METHODS: The study will include 150 patients with multivessel coronary artery disease (CAD) with left ventricle ejection fraction (LVEF) and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB); 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. DISCUSSION: The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice, the inappropriate use of these necrosis markers has led to misdiagnosis and therefore wrong treatment. The appearance of a more sensitive tool such as CMR provides an unprecedented diagnostic accuracy of myocardial damage when correlated with necrosis enzyme markers. We aim to correlate laboratory data with imaging, thereby establishing more refined data on the presence or absence of irreversible myocardial injury after the procedure, either percutaneous or surgical, and this, with or without the use of cardiopulmonary bypass.     

Rationalising requests for x-ray examination of acute ankle injuries.

Radiographs of injured ankles represent about 1 in 50 of all radiological examinations. The notes and radiographs of 100 patients with ankle injuries were reviewed, and the films of a further 93 patients who had ankle fractures treated by immobilisation were also scrutinised to assess the presence of absence of soft tissue swelling over the malleoli. Any accompanying radiographs of the foot requested at the same time were also studied. In 65 of the 100 cases of ankle injury there was no soft tissue swelling, and none of the patients had a major fracture, while 92 of the 93 patients with a major fracture had soft tissue swelling at the level of the malleoli. In 32 of the 100 cases of ankle injury foot radiographs had also been requested, but only three foot injuries were found. If the simple maxim of "No swelling adjacent to a malleolus, no radiographs" were applied radiography of twisted ankles could be reduced by as much as two-thirds. Moreover, if this maxim included the rider "and no routine foot films" the total casualty radiographic work load could be reduced by 8%.