Free Flap Limb Salvage and Ulcer Recurrence in Chronic Limb-threatening Ischemia.

Free flap transfer is a well-established treatment for foot reconstruction in patients with chronic limb-threatening ischemia (CLTI) and can achieve prolonged amputation-free survival. However, reports on ulcer recurrence after free flap transfer are scarce, with most focusing on trauma patients. Therefore, we retrospectively reviewed patients with CLTI who underwent free flap reconstruction at our institution over a 17-year period. Patient characteristics, ulcer recurrence rates, activity level, and variables associated with ulcer recurrence were investigated in patients who met the following criteria: successful reconstructive surgery, complete wound healing, and at least 1 year of follow-up. Free flap foot reconstruction was performed in 42 patients (92.9% male, 7.1% female; mean age 57.1 years, range 37-81 years). Among them, 39 patients (92.9%) had diabetes mellitus, 15 (35.7%) had critical limb ischemia, and 15 (35.7%) had end-stage renal disease/hemodialysis. Mean postoperative follow-up was 60.5 (range 12.0-208.0) months. The 5-year primary ulcer recurrence-free survival rate was 48.7%. High activity level and selection of the posterior tibial artery as the recipient artery were significantly associated with ulcer recurrence [hazard ratio, 3.59 and 9.81; P = .046 and P < .001, respectively]. Activity levels were not significantly different before and 1 year after surgery. In conclusion, survival analysis revealed that ulcer recurrence is most likely to occur within the first 2 years after surgery. Although recurrence occurred in approximately half of the patients, most patients maintained activity levels comparable to their preoperative levels.

Comparison of Subsequent Inframalleolar Bypass Surgery and Repeat Endovascular Therapy for Infrapopliteal Restenosis in Patients With Chronic Limb-Threatening Ischemia Undergoing Primary Endovascular Therapy.

PURPOSE: Although endovascular therapy (EVT) is considered a vital strategy for treating infrapopliteal lesions in chronic limb-threatening ischemia (CLTI), the recurrence rate after EVT exceeds that after bypass surgery (BSX). The optimal approach for managing infrapopliteal lesion recurrence in patients with CLTI and unhealed ulcers remains uncertain. This study aimed to evaluate the clinical outcomes of repeat EVT and subsequent inframalleolar BSX for CLTI with infrapopliteal lesion recurrence. MATERIALS AND METHODS: We conducted a retrospective analysis of 140 patients with CLTI (mean age, 70±10 years; male, 71.4%; diabetes mellitus, 73.6%; dialysis, 74.3%; Rutherford 5, 79.3%; and Rutherford 6, 20.7%) who had an unhealed wound due to the recurrence of infrapopliteal lesions between January 2015 and May 2020. We compared the clinical outcomes of 40 patients who underwent the subsequent inframalleolar BSX with those of 100 patients who underwent repeat EVT. The outcome measures were amputation-free survival (AFS) and wound healing rate. Propensity score matching analysis was conducted to minimize differences in baseline characteristics. RESULTS: Propensity score matching extracted 38 pairs (38 patients in the subsequent BSX group and 83 patients in the repeat EVT group). AFS was not significantly different between the repeat EVT and subsequent BSX groups (81.9% vs 82.6% at 1 year, p=0.97). Neither was cumulative wound healing (42.8% vs 43.3% at 1 year, p=0.55). No baseline characteristics had any significant interaction effect on the association between repeat EVT, subsequent BSX, and failure of AFS. CONCLUSION: This study using propensity score matching revealed that the clinical outcomes following repeat EVT were comparable with those following subsequent inframalleolar BSX, indicating that repeat EVT may be a viable treatment option for CLTI with infrapopliteal lesion recurrence. CLINICAL IMPACT: Although endovascular therapy (EVT) has expanded the treatment options for chronic limb-threatening ischemia (CLTI), the recurrence rate after EVT is higher than that after bypass surgery (BSX). This retrospective study compared the clinical outcomes of repeat EVT with those of subsequent BSX for CLTI with infrapopliteal lesion recurrence. After propensity score matching, amputation-free survival (AFS) was not significantly different between the repeat EVT and subsequent BSX groups (81.9% vs 82.6% at 1 year, p=0.97). Neither was cumulative wound healing (42.8% vs 43.3% at 1 year, p=0.55). There was no difference between the 2 revascularization strategies when treating infrapopliteal restenosis lesions.

A novel low-density lipoprotein/fibrinogen apheresis method for chronic limb-threatening ischemia in patients with poor options for revascularization: A multicenter, single-arm clinical trial.

INTRODUCTION: Low-density lipoprotein (LDL) apheresis is a treatment option for patients with unhealed chronic limb-threatening ischemia (CLTI) after revascularization. The newly developed AS-25 is a direct hemoperfusion-type apheresis device that differs from conventional LDL apheresis therapy and is designed to specifically adsorb both LDL-C and fibrinogen. We evaluate the efficacy and safety of AS-25. METHODS: This study included 61 patients whose ulcers failed to heal after revascularization or were ineligible for revascularization. Of these, 50 were undergoing hemodialysis. The primary endpoint was the healing rate of a target lesion of interest (ulcer), using historical data as control. RESULTS: The ulcer healing rate of 45.9% was significantly higher than the historical data. No significant safety concerns were observed. CONCLUSIONS: AS-25 was effective in healing ulcers and preventing major amputation even in CLTI refractory patients on hemodialysis, thus showing potential clinical applicability and high significance. CLINICAL TRIAL REGISTRATION: UMIN study ID UMIN000020336.

Free Flap Salvage in the Ischemic Foot: A Case Report.

We performed distal bypass and free flap transfer in a single-stage operation to repair an extensive soft tissue defect in an ischemic foot of an 84-year-old woman. The nutrient artery of the free flap was anastomosed to the bypass graft in an end-to-side manner. Subsequently, the bypass graft became occluded on several occasions. Although intravascular and surgical interventions were performed each time, the bypass graft eventually became completely occluded. However, despite late occlusion of the nutrient artery, the free flap has remained viable and the patient is ambulatory. The time required for a transplanted free flap to become completely viable without a nutrient artery is likely longer for an ischemic foot compared with a healthy foot. However, the exact period of time required is not known. A period of month was required in our patient. We report this case to help clarify the process by which a free flap becomes viable when applied to an ischemic foot.

Factors that Affected Functional Outcome After a Delayed Excision and Split-Thickness Skin Graft on the Dorsal Side of Burned Hands.

Early excision and skin grafting is the principle treatment for a burned hand although there are occasions when it cannot be done such as severe general condition, delayed consultation, and the lack of a definitive assessment of burn depth. This study analyzes the factors that affected function after a delayed excision and skin graft for hands with a deep dermal burn. This study retrospectively evaluated 43 burned hands that required a delayed excision and split-thickness skin graft on the dorsal side. Cases were required to only have split-thickness skin grafting from the dorsum of the hand and fingers distally to at least the proximal interphalangeal joint at least 8 days after the injury. The hands were divided into two functional categories: Functional category A, normal or nearly normal joint movements, and functional category B, abnormal joint movements. Demographic data were assessed statistically by a univariate analysis following a multiple regression analysis by a stepwise selection. A significant difference was observed between the groups in the number of days from grafting to complete wound healing of the graft site and with or without an escharotomy in the analysis. These parameters were statistically significant predictors of functional category B. The functional outcome of a burned hand after a delayed excision and split-thickness skin graft on the dorsal side became degraded depending on the number of days from grafting to complete wound healing. Cases that underwent an escharotomy also showed deterioration in function.

Detection of a novel silent deletion, a missense mutation and a nonsense mutation in TCOF1.

BACKGROUND: Treacher Collins syndrome (TCS) is a disorder of craniofacial development, that is caused by mutations in the TCOF1 gene. TCS is inherited as an autosomal dominant trait, and haploinsufficiency of the TCOF1 gene product treacle is proposed to be etiologically involved. METHODS: Mutational analysis of the TCOF1 gene was done in 10 patients diagnosed with TCS using single-strand conformation polymorphism and direct sequencing. RESULTS: Among these 10 patients, a novel 9 bp deletion was found, together with a previously reported 2 bp deletion, a novel missense mutation and a novel nonsense mutation in three different families. Familial studies allowed judgment of whether these abnormal findings were responsible for the TCS phenotype, or not. The 9 bp deletion of three amino acids Lys-Glu-Lys (1378-1380), which was located in the nuclear localization domain of treacle, seemed not essential for the treacle function. In contrast, the novel mutation of Ala26Val is considered to affect the LisH domain, an important domain of treacle. All of the mutations thus far detected in exon 5 have resulted in frameshift, but a nonsense mutation was detected (Lys159Stop). CONCLUSION: The information obtained in the present study provides additional insights into the functional domains of treacle.

Sentinel node biopsy versus elective lymph node dissection in patients with cutaneous melanoma in a Japanese population.

BACKGROUND: In Japan, elective lymph node dissection (ELND) has been the standard treatment for patients with possible nodal melanoma. Sentinel node biopsy (SNB) has now replaced ELND, not only in Japan but also worldwide. The objective of this study was to compare the interim outcomes of SNB and ELND. METHODS: A retrospective study was conducted among patients with clinically node-negative disease treated at our institute with either SNB (n = 30) or ELND (n = 72). RESULTS: The background was similar in the two groups. Nodal metastases were found in 40.0% of patients in the SNB group, but in only 26.4% in the ELND group (P = 0.173). The median follow-up was 31.5 months for the SNB group and 82 months for the ELND group. The incidence of locoregional recurrence and distant metastasis in the SNB group was 10.0% and 16.7%, respectively, and for the ELND group the incidence was 5.6% and 31.9%, respectively. The 3-year disease-free survival rate was similar in the two groups (P = 0.280), and the 3-year disease-free survival rates for node-positive patients were also similar in the two groups (P = 0.90), as were the 3-year disease-free survival rates for node-negative patients (P = 0.193). CONCLUSION: This interim result in a Japanese melanoma population with clinically node-negative disease demonstrated that SNB identified more nodal micrometastases than ELND. This increase in accurate staging likely resulted from the reliable identification of the lymph node field by lymphoscintigraphy, as well as the more detailed pathologic examination of the nodes removed in SNB. It is quite reasonable to perform SNB instead of ELND in this population.

New grading system for patients with treacher Collins syndrome.

Treacher Collins syndrome (TCS) is a congenital, craniofacial disorder affecting the development of structures derived from the first and second branchial arches. The associated clinical features and their severity are variable. Therefore, we reasoned that objective assessment of the clinical features and their severity in TCS is necessary to plan the treatment and to evaluate the outcome. We hereby propose a new grading system for Treacher Collins syndrome (TCS). Since 1978, 16 patients have been diagnosed with TCS. Eleven out of the 16 TCS patients, for whom we were able to estimate the severity of the clinical features in each region, and to make an objective assessment of the therapeutic outcomes, were selected. By allocating points according to the degree of severity of the clinical features in each region, then summing them up and categorizing them, we classified the overall clinical features into 3 grades. The severity increases from grades I to III. In summary, there were 3 patients of grade I, 4 patients of grade II and 4 patients of grade III. Distinctive differences regarding the degree of severity of the clinical features were clearly observed between each grade. We propose a new TCS grading system and applied it to 11 patients. We believe that this system may be useful for planning treatment and to evaluate the outcome in TCS patients.

Mutational analysis of the TCOF1 gene in 11 Japanese patients with Treacher Collins Syndrome and mechanism of mutagenesis.

Treacher Collins Syndrome (TCS) (OMIM 154500) is a congenital, craniofacial disorder inherited as an autosomal dominant trait. The responsible gene for TCS, TCOF1, was mapped to 5q32-33.1 and identified in 1996. Since then, TCOF1 mutations in patients with TCS have been reported from Europe, North and South America, however, no TCS cases from an Asian country have been molecularly characterized. Here we report mutational analysis for 11 Japanese patients with TCS for the first time, and have identified TCOF1 mutations in 9 of them. The mutations detected were various, but most likely all the mutations are predicted to result in a truncated gene product, known as treacle. One mutation frequently reported was included in our cases, but no missense mutations were detected. These findings are similar to those for the previous studies for TCS in other races. We have speculated about the molecular mechanisms of the mutations in most cases. Collectively, we have defined some of the characteristic molecular features commonly observed in TCS patients, irrespective of racial difference.

Treacher Collins syndrome with craniosynostosis, choanal atresia, and esophageal regurgitation caused by a novel nonsense mutation in TCOF1.

Treacher Collins syndrome (TCS) is caused by mutations in TCOF1 of the nonsense, small deletion, and small insertion types, which most likely result in haploinsufficiency. We report a novel de novo nonsense mutation 2731C --> T, resulting in Arg911Stop, which truncates the protein. Our patient had the classic findings of TCS, but with documented craniosynostosis, choanal atresia, and esophageal regurgitation.

Follow-up study of upper limb lymphedema patients treated by microsurgical lymphaticovenous implantation (MLVI) combined with compression therapy.

We present a follow-up study of 18 patients with upper limb lymphedema treated by microsurgical lymphaticovenous implantation (MLVI) combined with compression therapy. This combined technique provides increased lymphatic flow through newly created lymphaticovenous bypasses by the MLVI surgery, with assistance for pumping function in the lymphatics by compression therapy. Preoperative assessment of the affected limb was performed by the average enlargement of edema circumference (AEEC), comparing the lymphedema limb and normal limb circumferences. Objective improvement was analyzed by the percent reduction of edema circumference (%REC) at two levels of the lymphedema limb. With an average follow-up of 24 months, 77.8% of patients presented excellent or good results, with %REC >50% at either the distal or proximal site of the treated limb. This combined treatment can be expected to provide favorable long-term results, even for patients with AEEC >8 cm.