Comparison of the outcomes of free jejunal flap reconstructions of pharyngoesophageal defects in hypopharyngeal cancer and corrosive injury patients.

INTRODUCTION: Free jejunal flap is one of the optimal choices for restoring upper digestive tract. The purpose of this study was to introduce the treatment strategies and to compare the outcomes of free jejunal flap for pharyngoesophageal reconstruction between hypopharyngeal cancer and chemical corrosive injured esophagus. METHODS: From 2001 to 2012, patients who had been received esophageal reconstruction by free jejunal flap for pharyngoesophageal defect were divided into squamous cell carcinoma (SCC) group and corrosive chemical injury (CCI) group. All data on outcomes and complications including relevant radiographic investigations were collected retrospectively. RESULTS: Sixteen patients were in SCC group and 9 patients in CCI group underwent free jejunal flap reconstruction. Two cases of flap failure were noted in SCC group, and no flap failure in CCI group-the total failure rate was 8% (2/25 patients). In SCC group, 5 of 16 patients (31.3%) developed fistula; however, no fistula in CCI group. One patient in SCC group and 3 patients in CCI group developed esophageal strictures. Other than early stricture (stricture <1 year) which reached significant difference, all of other complications were not statistically significant between two groups. The average follow-up time was 42 months. CONCLUSIONS: Postoperative early stricture but lower fistula occurrence is expected in patients with corrosively injured esophagi. This helpful preliminary findings could not only early-check complication, but also better explanation and prepare were taken placed before operation.

The First Hand Allotransplantation in Taiwan: A Report at 9 Months.

PURPOSE: Hand transplantations have been initiated and have been encouraged by promising results for more than 1 decade. The aim of this study was to present the first case of hand transplantation performed in Taiwan. MATERIALS AND METHODS: On September 3, 2014, we transplanted the left distal forearm and hand of a brain-dead managed 37 years to a man aged 45 years who had traumatic amputation of the distal third of his right forearm 30 years ago. The total ischemic time during the transplantation was 6 hours and 45 minutes. Immunosuppression included anti-thymocyte globulins, and methylprednisolone (Solumedrol) was used for the induction. Maintenance therapy included systemic tacrolimus, mycophenolic acid [mycophenolate mofetil (MMF)], and prednisone. A combination of systemic (tacrolimus/MMF/prednisolone) and topical immunosuppressant cream (clobetasol and tacrolimus) was applied if acute rejection occurred. Follow-up included routine posttransplant laboratory tests, skin biopsies, intensive physiotherapy, and psychological support. RESULTS: The initial postoperative course was uneventful. No surgical complications were observed. Immunosuppression was well tolerated using tacrolimus, MMF, and prednisone, except for some immune-related complications. One episode of mild clinical and histological signs of cutaneous rejection was seen at 105 days after surgery. These signs disappeared after pulse therapy with Solumedrol and the topical application of immunosuppressive creams (tacrolimus and clobetasol). One infection episode occurred due to local cellulitis and axillary lymphadenopathy on day 140 and was successfully treated with antibiotics. The patient developed cytomegalovirus infection at 7 months that responded to medication. Intensive physiotherapy led to satisfactory progress in motor functioning. Sensory progress (Tinel sign) was good and reached the wrist by 3 months for the median and ulnar nerves, and could be felt in the finger tip by 9 months in response to deep pressure and light touch sensations. The patient has a lateral pinch that allows him to pick up and grip objects during daily living, although his muscle power is still insufficient. CONCLUSIONS: Hand allotransplantation is technically feasible. Currently available immunosuppression methods seem to control vascularized composite tissue allotransplantation rejection. A combination of topical and systemic immunosuppressants is a useful method to prevent acute hand allotransplant rejection.

The new innovation of the lower medial thigh perforator flap for head and neck reconstruction.

BACKGROUND: The choice of optimal flap is still a challenge for patients with resection of head and neck cancer and reconstruction, especially for recurrent cases. In this article, we report the results of the new innovation of free lower medial thigh perforator (LMTP) flap for head and neck reconstruction in a series of patients. PATIENTS AND METHODS: Fifteen patients received reconstruction with free LMTP flaps. The defect locations included the buccal area (3 cases), tongue (6 cases), lower/upper gum (5 cases), and soft palate (1 case). The perforators of flap design were detected at the distal third of the line, which was drawn from the midpoint of inguinal ligament to medial upper border of patella. The superficial temporal artery (7 cases), superior thyroid artery (6 cases), and facial artery (2 cases) were dissected as recipient vessels. RESULTS: The flap sizes varied from 12 × 5 cm(2) to 20 × 8 cm(2) . One to two perforators based on the superficial femoral artery or descending genicular artery were found between the septum of satorius and vastus medialis, or piercing the vastus medialis during dissection. All of flaps were survived after surgery, except one failed due to venous thrombosis. Another one flap suffered from venous thrombosis and was successfully salvaged by performing a venous thrombectomy. All donor sites were primarily closed except one skin grafting. The follow-up time ranged from 3 to 15 months (average: 7 months) and all patients had good recovery with satisfactory results. CONCLUSION: The LMTP flap indicates a pliable with constant vascular anatomy and low donor-site morbidity. It could be an alternative for reconstructing defects in head and neck region. © 2015 Wiley Periodicals, Inc. Microsurgery 36:284-290, 2016.

An objective comparison regarding rate of fistula and stricture among anterolateral thigh, radial forearm, and jejunal free tissue transfers in circumferential pharyngo-esophageal reconstruction.

BACKGROUND: The three commonly used free flaps for circumferential pharyngeal reconstruction after total pharyngo-laryngectomy are the radial forearm flap (RFF), the anterolateral thigh (ALT) flap, and the jejunum flap. This study was to objectively compare three different flaps for pharyngeal reconstruction during the past 10 years. Stricture and fistula were assessed using esophagogram and esophagoscopy. METHODS: Forty-five patients with pharyngeal reconstructions had esophagram and esophagoscopy done postoperatively to assess for strictures and fistulas. These patients were divided into three groups based on pharyngeal reconstruction by ALT, RFF, and jejunal flaps. From the results of the esophagogram and esophagoscope, the presence of a fistula or stricture was compared and analyzed. RESULTS: There was only one ALT flap failure. The rate of fistula was 33%, 50%, and 30% in the ALT, RFF, and jejunal flap group respectively. The fistula rate revealed no significant difference between ALT, RFF, jejunal flap groups (P = 0.63). The rate of stricture was 38.1%, 57.1%, and 0% in the ALT, RFA, jejunal flap groups respectively. The stricture rate in jejunal flap group revealed significant decrease (P = 0.0093). CONCLUSION: Jejunal flap has a significantly lower rate of stricture for reconstruction of circumferential pharyngeal defects when compared with RFF or ALT flaps.

Levels and values of lipoprotein-associated phospholipase A2, galectin-3, RhoA/ROCK, and endothelial progenitor cells in critical limb ischemia: pharmaco-therapeutic role of cilostazol and clopidogrel combination therapy.

OBJECTIVE: We tested the hypothesis that clopidogrel and cilostazol combination therapy could effectively attenuate systemic inflammatory reaction, facilitate proliferation of circulating endothelial progenitor cell (EPC), and improve the clinical outcomes of critical limb ischemia (CLI) in patients unsuitable for surgical revascularization or percutaneous transluminal angioplasty (PTA). METHODS: A total 55 patients (mean age, 72 years; 56% female) were consecutively enrolled. Clopidogrel and cilostazol combination therapy was administered throughout the study period. RESULTS: As compared with the baseline, circulating endothelial progenitor cell level (as shown by flow cytometry) was significantly increased (p<0.003), whereas the CLI-related ulcers and painfulness were significantly improved (all p<0.01) by day 90 after treatment. On the other hand, after clopidogrel and cilostazol combination therapy, galectin-3 level, lipoprotein-associated phospholipase A2 gene expression, and RhoA/ROCK-related protein expression in peripheral blood mononuclear cells were significantly suppressed (all p<0.01). Eventually, by day 90, 5 patients (9.1%) died of other etiologies, 3 (5.5%) withdrew from the study, 6 (10.9%) required amputation, and the remaining 41 had satisfactory clinical improvement with complete wound healing in 9 (16.4%) patients. CONCLUSION: The results of the present study highlight that clopidogrel and cilostazol combination therapy may be considered to be an alternative method for treating patients with CLI unsuitable for surgical revascularization or PTA.

Free tissue transfers in head and neck reconstruction: complications, outcomes and strategies for management of flap failure: analysis of 2019 flaps in single institute.

BACKGROUND: Free tissue transfer has become the preferred option for complex reconstructions in head and neck cancer ablation. This study reviewed the surgical outcome and analyzed the evolution of microsurgical head and neck reconstruction over 20 years in single institute. PATIENTS AND METHODS: A total of 1,918 patients underwent microsurgical head and neck reconstructions in 20-year period. The surgical outcome and complications among these 2,019 flaps (1,223 anterolateral thigh flaps, 372 fibula flaps, 353 radial forearm flaps, 12 jejunal flaps, and 59 others) were retrospectively reviewed and analyzed. RESULTS: A total of 201 cases required emergent surgical re-exploration and the overall flap success rate was 96.2%. Venous insufficiency was the most common cause for re-exploration. Other major complications included fistula formation (5.4%), partial flap necrosis (7.5%), and infection (17.8%). The fibula flap had frequent complications compared with soft tissue flaps. The familiarity to the ALT flap had minimized complications and allowed for widely versatile uses. CONCLUSION: Free tissue transfer is shown to be highly reliable option for head and neck reconstruction. For soft tissue defect, ALT flap is the first choice. Fibula flap is ideal for bone defect reconstruction. In case of complex composite defects, double flaps, which include ALT and fibula flaps could reconstruct bone and soft tissue defects simultaneously with high success rate.

Comparison of outcomes of pressure sore reconstructions among perforator flaps, perforator-based rotation fasciocutaneous flaps, and musculocutaneous flaps.

BACKGROUND: Pressure sore reconstruction remains a significant challenge for plastic surgeons due to its high postoperative complication and recurrence rates. Free-style perforator flap, fasciocutaeous flap, and musculocutaneous flap are the most common options in pressure sore reconstructions. Our study compared the postoperative complications among these three flaps at Kaohsiung Chang Gung Memorial Hospital. METHODS: From 2003 to 2012, 99 patients (54 men and 45 women) with grade III or IV pressure sores received regional flap reconstruction, consisting of three cohorts: group A, 35 free-style perforator-based flaps; group B, 37 gluteal rotation fasciocutaneous flaps; and group C, 27 musculocutaneous or muscle combined with fasciocutaneous flap. Wound complications such as wound infection, dehiscence, seroma formation of the donor site, partial or complete flap loss, and recurrence were reviewed. RESULTS: The mean follow-up period for group A was 24.2 months, 20.8 months in group B, and 19.0 months for group C. The overall complication rate was 22.9%, 32.4%, and 22.2% in groups A, B, and C, respectively. The flap necrosis rate was 11.4%, 13.5%, and 0% in groups A, B, and C, respectively. There was no statistical significance regarding complication rate and flap necrosis rate among different groups. CONCLUSIONS: In our study, the differences of complication rates and flap necrosis rate between these groups were not statistically significant. Further investigations should be conducted.

The outcome of free tissue transfers in patients with hematological diseases: 20-year experiences in single microsurgical center.

BACKGROUND: Free tissue transfers performed in patients with hematological diseases represent significant challenges for micro-surgeons. There are rare literatures that address the outcome in these patients. Therefore, we collected our database, analyzed the outcome, reliability, and related-management of microsurgical technique in the patients with hematological diseases. METHODS: A retrospective chart review of 20 patients with hematological disorders who received free tissue transfers during 20-years period in a single microsurgical center was done. Eleven patients who received head and neck reconstruction were found to have hyperfibrinogenemia. Seven patients with reactive thrombocytosis after trauma, and two patients with leukemia had soft tissue defects in the upper and lower extremities. Twenty-six flaps were used for free tissue transfers. Intra-operatively all patients received intravenous 5,000 Ud of heparin post immediate reperfusion. Anti-coagulant medication such as Dextran-40 or prostaglandin-E1 (PGE1) was given postoperatively. RESULTS: Twenty-three of the 26 free flaps survived without vascular compromise. Intra-operatively all patients received intravenous 5,000 Ud of heparin post immediate reperfusion, and anti-coagulant medication such as Dextran-40 or prostaglandin-E1 was given to the patients postoperatively. The three failed cases were found in patients with hyperfibrinogenemia and needed further reconstruction with another flap. The overall success rate was 88.5% (23/26). CONCLUSIONS: Hematologic disorder is not a predicted factor of free flap failure. The key factors for success flap survival in patients with hematologic disorders include preoperative knowledge of the medical condition and monitoring potential post-operative complications, aggressive hematologist consultations, and meticulous non-traumatic surgical anastomosis.

The role of the anterolateral thigh flap in complex defects of the scalp and cranium.

In this study, we introduced scalp reconstruction using free anterolateral thigh (ALT) flaps and evaluated postoperative outcomes in nine patients between March 2000 and April 2012. Five patients had problems of exposed prosthesis, three required reconstruction after resection of scalp tumor and one patient presented with third degree flame burns of the scalp. All flaps survived without re-exploration, except three flaps with tip necrosis requiring secondary procedures of debridement and small Z-plasty reconstructions. The superficial temporal artery and its concomitant vein were used as recipient vessels, apart from two cases where previous surgery and flame burns excluded these choices, for which facial arteries and veins were used instead. Primary closure of the donor-site was possible in six cases; with skin grafting performed for the other three patients. All donor sites healed without complications. The ALT flap offers the advantage of customizable size, option of fascia lata as vascularized dural replacement, and minimal flap atrophy typical of muscle flaps. Indications include very large defects, defects with exposed prosthesis, or defects with bone or dural loss. Our experience lends credible support to the use of customized free ALT flaps to achieve functional and cosmetically superior result for the reconstruction of large scalp defects, especially with bone exposure.

Influence of neck dissection and preoperative irradiation on microvascular head and neck reconstruction-Analysis of 853 cases.

BACKGROUND: Previous neck dissection and irradiation is believed to affect the success of free tissue transfers in head and neck reconstruction, but evidence is scarce and conflicting. This study seeks to evaluate flap success rates in the presence of these two factors. METHODS: Over a ten-year period, a total of 853 free flap cases were evaluated. Success rates were compared between a control group with no prior intervention (non-irradiation and neck dissection, NRTND) against three other groups: irradiation only (RT), previous neck dissection only (ND), and both (RTND). The choices of recipient vessel used were also compared. RESULTS: The flap failure rate was 6.3% (4/63) in the RTND group; 4.8% (1/21) in the ND group; 5.2% (6/115) in the RT group; and 2.1% (14/654) in the NRTND group. There was no statistical significance among the four groups (P = 0.254). Ipsilateral neck vessels (92.7%) were more frequently used in the NRTND group. In contrast, the superficial temporal vessels, contra-lateral neck vessels were more likely to be selected in the groups with irradiation and/or neck dissection. CONCLUSIONS: Free tissue transfer in head and neck patients with previous irradiation and neck dissection is feasible and can be safely done. In addition, superficial temporal vessel could be the first choice in patients with previous radiotherapy and neck dissection.

Surgical site infections among high-risk patients in clean-contaminated head and neck reconstructive surgery: concordance with preoperative oral flora.

BACKGROUND: Salivary contamination of surgical wounds in clean-contaminated head and neck surgery with free flap reconstruction remains a major cause of infection and leads to significant morbidity. This study investigates the correlation between intraoral flora and surgical site infections (SSIs) among high-risk head and neck cancer patients undergoing resection and free flap reconstruction. METHODS: One hundred twenty-nine patients were identified as being at high risk for infective complications based on cancer stage, tumor size, comorbid factors, and extent of reconstruction. All patients had intraoral swab cultures before surgery. Patients with culture-confirmed SSI after surgery were chosen for analysis, using the κ index and its 95% confidence interval for concordance analysis. All patients received clindamycin and gentamicin for antibiotic prophylaxis for 5 days. Antibiotic susceptibility testing of all isolates was obtained and analyzed. RESULTS: Thirty-seven patients experienced SSI, or an infection rate of 28.3%, occurring at a mean of 9.3 postoperative days. The overall concordance between oral flora and SSI was fair to moderate (κ index of 0.25), but detailed analysis shows a higher concordance for known and opportunistic pathogens, such as Pseudomonas aeruginosa and Enterococcus faecalis, compared to typical oral commensals. Antibiotic susceptibility tests show rapid and significant increases in resistance to clindamycin, indicating a need for a more effective alternative. CONCLUSIONS: Predicting pathogens in SSI using preoperative oral swabs did not demonstrate a good concordance in general for patients undergoing clean-contaminated head and neck surgery, although concordance for certain pathogenic species seem to be higher than for typical intraoral commensals. The rapid development of resistance to clindamycin precludes its use as a prophylactic agent.

Risk factors for pressure ulcer recurrence following surgical reconstruction: A cross-sectional retrospective analysis.

Many studies on the recurrence of pressure ulcers after surgical reconstruction have focused on surgical techniques and socioeconomic factors. Herein, we aimed to identify the risk factors of the associated comorbidities for pressure ulcer recurrence. We enrolled 147 patients who underwent pressure ulcer reconstruction and were followed up for more than three years. The recurrence of pressure ulcers was defined as recurrent pressure ulcers with stage 3/4 pressure ulcers. We reviewed and analyzed systematic records of medical histories, including sex, age, associated comorbidities such as spinal cord injury (SCI), diabetes mellitus (DM), coronary artery disease, cerebral vascular accident, end-stage renal disease, scoliosis, dementia, Parkinson's disease, psychosis, autoimmune diseases, hip surgery, and locations of the primary pressure ulcer. Patients with recurrent pressure ulcers were younger than those without. Patients with SCI and scoliosis had higher odds, while those with Parkinson's disease had lower odds of recurrence of pressure ulcers than those without these comorbidities. Moreover, the decision tree algorithm identified that SCI, DM, and age < 34 years could be risk factor classifiers for predicting recurrent pressure ulcers. This study demonstrated that age and SCI are the two most important risk factors associated with recurrent pressure ulcers following surgical reconstruction.

Mesenchymal stem cells as immunomodulators in a vascularized composite allotransplantation.

Vascularized composite allotransplantations (VCAs) are not routinely performed for tissue reconstruction because of the potentially harmful adverse effects associated with lifelong administration of immunosuppressive agents. Researchers have been eagerly seeking alternative methods that circumvent the long-term use of immunosuppressants. Mesenchymal stem cells (MSCs) show promise as an immunomodulatory therapeutic agent and are currently being tested in preclinical and clinical settings as therapies for autoimmune disorders or transplant rejection. The mechanisms by which MSCs modulate the immune response are still under thorough investigation, but these most likely involve expression of local factors influencing T-cell regulation, modulation of cytokine expression (e.g., IL-10, TGF-ß, TNF-α, INF-γ, etc.), and interactions with dendritic or antigen presenting cells. In this paper, we summarize the current understanding of immunomodulation achieved by MSC therapies and introduce a possible outline for future clinical applications in VCA.

A reusable perforator-preserving gluteal artery-based rotation fasciocutaneous flap for pressure sore reconstruction.

BACKGROUND: Perforator-based fasciocutaneous flaps for reconstructing pressure sores can achieve good functional results with acceptable donor site complications in the short-term. Recurrence is a difficult issue and a major concern in plastic surgery. In this study, we introduce a reusable perforator-preserving gluteal artery-based rotation flap for reconstruction of pressure sores, which can be also elevated from the same incision to accommodate pressure sore recurrence. METHODS: The study included 23 men and 13 women with a mean age of 59.3 (range 24-89) years. There were 24 sacral ulcers, 11 ischial ulcers, and one trochanteric ulcer. The defects ranged in size from 4 × 3 to 12 × 10 cm(2) . Thirty-six consecutive pressure sore patients underwent gluteal artery-based rotation flap reconstruction. An inferior gluteal artery-based rotation fasciocutaneous flap was raised, and the superior gluteal artery perforator was preserved in sacral sores; alternatively, a superior gluteal artery-based rotation fasciocutaneous flap was elevated, and the inferior gluteal artery perforator was identified and dissected in ischial ulcers. RESULTS: The mean follow-up was 20.8 (range 0-30) months in this study. Complications included four cases of tip necrosis, three wound dehiscences, two recurrences reusing the same flap for pressure sore reconstruction, one seroma, and one patient who died on the fourth postoperative day. The complication rate was 20.8% for sacral ulcers, 54.5% for ischial wounds, and none for trochanteric ulcer. After secondary repair and reconstruction of the compromised wounds, all of the wounds healed uneventfully. CONCLUSIONS: The perforator-preserving gluteal artery-based rotation fasciocutaneous flap is a reliable, reusable flap that provides rich vascularity facilitating wound healing and accommodating the difficulties of pressure sore reconstruction.

Simultaneous reconstruction of head and neck defects following tumor resection and trismus release with a single anterolateral thigh donor site utilizing a lateral approach to flap harvest.

BACKGROUND: An anterolateral thigh (ALT) flap has gradually become the workhorse flap of reconstructions at different anatomical locations because of its reliability and versatility. In this study, we introduced the concepts: one is the ALT flap harvest from a lateral approach and the other is the reconstruction of extensive head and neck defects with a single ALT donor site. METHODS: A lateral approach ALT flap was harvested in 13 patients who had buccal cancer and/or tumors of the lower lip combined with buccal trismus. Three types of ALT flaps (type I: two skin paddles, one pedicle; type II: two skin paddles, two pedicles; type III: one skin paddle, one pedicle) were used in one-stage reconstructions of these extensive head and neck defects. RESULTS: In our series, there were four type I, five type II, and four type III flaps. All flaps survived and no major postoperative complication occurred. Four of the 13 donor sites were repaired with a split-thickness skin graft harvested from the contralateral thigh. The immediate interincisor distance increase was 21.4 and 16.5 mm at 1-year follow-up. CONCLUSIONS: Different types of ALT flap from a single donor site can be designed by means of a lateral approach; and the satisfactory results of reconstruction for extensive head and neck defects following the tumor resection and trismus release can be achieved.

The outcome of prostaglandin-E1 and dextran-40 compared to no antithrombotic therapy in head and neck free tissue transfer: analysis of 1,351 cases in a single center.

Free tissue transfer has become a popular technique for soft tissue defect reconstruction in head and neck cancer ablation. Although high success rates and good reliability of free flaps are proven, microvascular thrombosis is still the most critical issue for microsurgeons. Pharmacological antithrombotic agents are widely used but their efficacy is still debated. In this study, we analyzed whether prostaglandin-E1 (PGE1) and dextran-40 can improve the outcomes compared to no antithrombotic therapy at all. We retrospectively reviewed 1,351 free flaps performed for head and neck reconstruction after cancer ablation. Three groups defined were 232 flaps received PGE1, 283 flaps received dextran-40, and 836 received no antithrombotic therapy. The demographics of these three groups indicated no statistical differences. The results showed that flap survival revealed no significant difference among PGE1, dextran-40, and control group (P = 0.734). There was a tendency to hematomas in PGE1 group (P = 0.056) when compared with other two groups. Dextran-40 significantly increased flap failure rate in high-risk patients with diabetes mellitus (P = 0.006) or hypertension (P = 0.003), when compared with PGE1 and control group. These results revealed antithrombotic therapy with PGE1 and dextran-40 do not determine a significant improvement in flap survival.

An ideal method for pressure sore reconstruction: a freestyle perforator-based flap.

BACKGROUND: Pressure sore reconstruction is quite difficult for plastic surgeons because of long-term high recurrence rates. We designed a freestyle perforator-based flap for pressure sore reconstruction considering pressure sore recurrence and further reconstruction. METHODS: We used a handheld Doppler device to locate a perforator position just adjacent to the pressure ulcer. In a series of 34 patients, we used 37 perforator-based flaps to reconstruct 25 sacral, 5 ischial, and 4 trochanteric ulcers. RESULTS: Twenty-eight of 37 flaps healed uneventfully without complication. One patient had a flap that totally necrosed, 3 had partial flap necrosis, 3 had wound dehiscence, 1 died 3 days postoperatively, and recurrence developed in 1 patient. CONCLUSIONS: We used the freestyle perforator-based fasciocutaneous flap for pressure sore management with good success. These flaps are easy to design and provide good versatility for coverage. Cooperation of surgical skills and good postoperative care also contributed to the lower recurrence rates and satisfactory results.

Effect of a Novel Macrophage-Regulating Drug on Wound Healing in Patients With Diabetic Foot Ulcers: A Randomized Clinical Trial.

Importance: Delayed healing of diabetic foot ulcers (DFUs) is known to be caused by dysregulated M1/M2-type macrophages, and restoring the balance between these macrophage types plays a critical role in healing. However, drugs used to regulate M1/M2 macrophages have not yet been studied in large randomized clinical trials. Objective: To compare the topical application of ON101 cream with use of an absorbent dressing (Hydrofiber; ConvaTec Ltd) when treating DFUs. Design, Setting, and Participants: This multicenter, evaluator-blinded, phase 3 randomized clinical trial was performed in 21 clinical and medical centers across the US, China, and Taiwan from November 23, 2012, to May 11, 2020. Eligible patients with debrided DFUs of 1 to 25 cm2 present for at least 4 weeks and with Wagner grade 1 or 2 were randomized 1:1 to receive ON101 or control absorbent dressings. Interventions: Twice-daily applications of ON101 or a absorbent dressing changed once daily or 2 to 3 times a week for 16 weeks, with a 12-week follow-up. Main Outcomes and Measures: The primary outcome was the incidence of complete healing, defined as complete re-epithelialization at 2 consecutive visits during the treatment period assessed on the full-analysis set (FAS) of all participants with postrandomization data collected. Safety outcomes included assessment of the incidences of adverse events, clinical laboratory values, and vital signs. Results: In the FAS, 236 eligible patients (175 men [74.2%]; mean [SD] age, 57.0 [10.9] years; mean [SD] glycated hemoglobin level, 8.1% [1.6%]) with DFUs classified as Wagner grade 1 or 2 (mean [SD] ulcer area, 4.8 [4.4] cm2) were randomized to receive either the ON101 cream (n = 122) or the absorbent dressing (n = 114) for as long as 16 weeks. The incidence of complete healing in the FAS included 74 patients (60.7%) in the ON101 group and 40 (35.1%) in the comparator group during the 16-week treatment period (difference, 25.6 percentage points; odds ratio, 2.84; 95% CI, 1.66-4.84; P < .001). A total of 7 (5.7%) treatment-emergent adverse events occurred in the ON101 group vs 5 (4.4%) in the comparator group. No treatment-related serious adverse events occurred in the ON101 group vs 1 (0.9%) in the comparator group. Conclusions and Relevance: In this multicenter randomized clinical trial, ON101 exhibited better healing efficacy than absorbent dressing alone in the treatment of DFUs and showed consistent efficacy among all patients, including those with DFU-related risk factors (glycated hemoglobin level, ≥9%; ulcer area, >5 cm2; and DFU duration, ≥6 months). Trial Registration: ClinicalTrials.gov Identifier: NCT01898923.

Microsurgical replantation and salvage procedures in traumatic ear amputation.

PURPOSE: The purpose of this study is to present our experience with patients who underwent traumatic ear amputation. METHODS: Between January 1988 and April 2002, 10 patients sustained ear amputations. Of these, six patients underwent microvascular replantation (arterial anastomosis only and arterial and venous anastomosis in three patients each), and replantation was attempted in one patient. However, no suitable vessel could be found for the anastomosis, and the amputated ear was treated as a composite graft and buried in a retroauricular pocket. Staged costal cartilage reconstruction was performed in three patients who lost the ear replant after trauma (two patients) or due to infection (one patient). RESULTS: The ear replant survived and showed good cosmetic results in the three patients who underwent arterial and venous anastomoses. The patients who had artery anastomosis only required intrareplant heparin injection (chemical leech) to resolve venous congestion and sustained partial loss of the replanted ear. Secondary procedures were necessary to repair the reconstructions, including an advancement, temporoparietal fascia, or retroauricular flap. Those who underwent staged ear reconstruction had late ear deformities. CONCLUSION: Microvascular replantation is the best method for reattaching an amputated ear, giving excellent esthetic results. If only arterial anastomosis is performed, a chemical leech is an option for decompressing the venous congestion. In those patients without a suitable vessel for microanastomosis, nonmicrosurgical methods are suggested, such as a temporoparietal fascia flap, retroauricular pocket procedure, or staged-costal cartilage reconstruction, depending on the ear defect.

Hyperbaric oxygen facilitates the effect of endothelial progenitor cell therapy on improving outcome of rat critical limb ischemia.

We tested the hypothesis that hyperbaric oxygen (HBO) (100% oxygen/2.4 atmospheres) facilitated the effect of autologous endothelial progenitor cell (EPC) therapy on restoring the blood flow in rat critical-limb ischemia (CLI). Adult-male-SD rats (n = 8/each group) were categorized into group 1 [sham control (SC)], group 2 (CLI-treated with culture medium), group 3 [CLI-intermittent HBO (3 h/day for 5 consecutive days after CLI), group 4 (CLI-EPC/2.0 × 106 cells), and group 5 (CLI-HBO-EPC). By day 5 after CLI, flow cytometry showed that the circulating EPC (Sca-1/CD31+/C-kit/CD31+/CD34+) levels were highest in group 5 and lowest in group 2 (all P < 0.001). By day 14, laser Doppler demonstrated that the ratio of blood flow (i.e., CLI to normal hind-limb) was highest in group 1, lowest in group 2 and significantly higher in group 5 than in groups 3 and 4 (all P < 0.0001). The protein expressions of endothelial-cell biomarkers (CD31/vWF/eNOS), and numbers of endothelial-cell markers (CD31+/vWF+) and small vessels exhibited a similar pattern to blood-flow ratio among five groups, whereas the angiogenesis parameters in protein (CXCR4/SDF-1α/HIF-1α/VEGF) and cellular (HIF-1α/SDF-1α/CXCR4+) levels were progressively increased from groups 1 to 5 (all P < 0.0001). The protein expression of apoptotic (mitochondrial-Bax/cleaved-capspase-3/PARP), fibrotic (p-Smad3/TGF-ß) and mitochondrial-damaged (cytosolic-cytochrome C) exhibited an opposite pattern, whereas the protein expressions of anti-fibrotic (BMP-2/p-Smad1/5) and mitochondrial integrity (mitochondrial-cytochrome C) exhibited an identical pattern of ratio of blood flow among the five groups (all P < 0.0001). Combined HBO-EPC therapy is superior to either one alone in improving ischemia in rodent CLI.