Multidisciplinary management of diabetic foot infection associated with improved 8-year overall survival.

AIMS: Diabetic foot syndrome is a global challenge best managed through multidisciplinary collaboration. This study aimed to investigate the effect of a systematic multidisciplinary team (MDT) on the overall survival and major amputation-free survival of hospitalized patients with diabetic foot infection (DFI). METHODS: This retrospective cohort study was conducted at Tampere University Hospital. Cohorts of hospitalized patients with DFI before and after the initiation of multidisciplinary wound ward were compared after an 8-year follow-up. RESULTS: Kaplan-Meier analysis revealed significantly higher overall survival in the post-MDT cohort (37.8 % vs 22.6 %, p < 0.05) in 8-year follow-up. Similarly, major amputation-free survival was superior in this cohort (31.8 % vs 16.9 %, p < 0.05). Additionally, early major amputation was associated with inferior overall survival (35.1 % vs 12.0 %, p < 0.05). In a multivariable Cox-regression analysis cohort (hazard ratio [HR] 1.38, 95 % confidence interval [CI95%] 1.01-1.87), early amputation (HR 1.64, CI95% 1.14-2.34) and diagnosed peripheral artery disease (HR 2.23, CI95% 1.61-3.09), congestive heart failure (HR 2.13, CI95% 1.47-3.08), or moderate kidney disease (HR 1.95, CI95% 1.34-2.84) were identified as significant risk factors affecting overall survival. CONCLUSIONS: After systematic MDT approach we found improved long-term overall and major amputation-free survival. Multidisciplinary approach is therefore highly recommended for managing patients hospitalized for DFI.

Myofibroblasts reside in the middle dermis of the keloids but do not predict the response to injection therapies: a double-blinded, randomized, controlled trial.

Introduction: Keloids form as a pathological response to skin wound healing, and their etiopathology is poorly understood. Myofibroblasts, which are cells transformed from normal fibroblasts, are believed to contribute to pathological scar formation in wounds. Methods: We carried out a double-blinded randomized controlled trial (RCT) comparing the efficacy of intralesional 5-fluorouracil (5-FU) and triamcinolone (TAC) injections in treating keloids. A total of 43 patients with 50 keloids were treated with either intralesional TAC or 5-FU injections, and their clinical response was evaluated. Biopsies were collected before, during, and after injection therapy from the active border of a keloid. To understand the role of myofibroblasts in keloids, we conducted an immunohistochemical analysis to identify myofibroblasts [α-smooth muscle actin (αSMA)] from the biopsies. We first defined the three histologically distinct regions-superficial, middle, and deep dermis-in each keloid. Results: We then demonstrated that myofibroblasts almost exclusively exist in the middle dermis of the keloids as 80% of the cells in the middle dermis were αSMA positive. However, both the percentage of myofibroblasts as well as the area covered by them was substantially lower in the superficial and deep dermis than in the middle dermis of the keloids. Myofibroblasts do not predict the clinical response to intralesional injection therapies. There is no difference in the myofibroblast numbers in keloids or in the induced change in myofibroblasts between the responders and non-responders after treatment. Discussion: This study demonstrates that myofibroblasts reside almost exclusively in the middle dermis layer of the keloids, but their numbers do not predict the clinical response to intralesional injection therapies in the RCT.

ESPRAS Survey: National and European Societies for Plastic Surgeons.

BACKGROUND: The European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS) comprises 40 national societies across Europe. In addition to ESPRAS, there are 8 different European Plastic Surgery societies representing Plastic Surgeons in Europe. The 4th European Leadership Forum (ELF) of ESPRAS, held under the motto "Stronger together in Europe" in Munich in 2023, aimed to collect and disseminate information regarding the national member societies of ESPRAS and European societies for Plastic Surgeons. The purpose was to identify synergies and redundancies and promote improved cooperation and exchange to enhance coordinated decision-making at the European level. MATERIAL AND METHODS: An online survey was conducted regarding the organisational structures, objectives and challenges of national and European societies for Plastic Surgeons in Europe. This survey was distributed to official representatives (Presidents, Vice Presidents and General Secretaries) and delegates of national and European societies at the ELF meeting. Missing information was completed using data obtained from the official websites of the respective European societies. Preliminary results were discussed during the 4th ELF meeting in Munich in March 2023. RESULTS: The ESPRAS survey included 22 national and 9 European Plastic Surgery societies representing more than 7000 Plastic Surgeons in Europe. Most national societies consist of less than 500 full members (median 182 members (interquartile range (IQR) 54-400); n=22). European societies, which covered the full spectrum or subspecialities, differed in membership types and congress cycles, with some requiring applications by individuals and others including national societies. The main purposes of the societies include research, representation against other disciplines, specialisation and education as well as more individual goals like patient care and policy regulation. CONCLUSION: This ESPRAS survey offers key insights into the structures, requirements and challenges of national and European societies for Plastic Surgeons, highlighting the relevance of ongoing close exchange between the societies to foster professional advancement and reduce redundancies. Future efforts of the ELF will continue to further explore strategies for enhancing collaboration and harmonisation within the European Plastic Surgery landscape.

Myth-busting the zone of injury concept: a prospective study on the vascular response to high-energy lower extremity trauma.

BACKGROUND: Although the zone of injury concept is widely accepted, no histologic studies of vessel wall changes causing the phenomena are reported. This prospective study investigated the vascular response to high-energy lower extremity trauma to evaluate the validity of the zone of injury concept. METHODS: The histologic appearance of arterial and venous walls in the zone of injury was studied in 19 patients (median age 46 [interquartile range 29.5-62.5] years) who underwent osteosynthesis and free-flap reconstruction due to high-energy lower extremity open fracture. Vascular samples were harvested from the injured extremity and control samples were harvested from the free-flap donor site. Histologic and morphometric characteristics of the vessels were analyzed microscopically and using digital pathology QuPath software. RESULTS: Vascular samples were harvested on post-injury days 1-11. Intimal thickness was >3 times greater in arteries harvested from the zone of injury than in control samples (P<0.01) and the intima/media ratio was 2-fold that in control samples (P=0.01). Arterial intimal fibrosis was more evident in vessels harvested from the zone of injury (P<0.01), but medial fibrosis and medial thickness did not differ significantly between groups. Venous intimal thickening (P<0.01) and the intima/media ratio (P=0.02) were superior in samples from the zone of injury. Fibrosis-related changes did not differ between groups (P=0.45). CONCLUSIONS: These findings support the validity of the zone of injury concept by providing a novel histologic basis for this phenomenon. Intimal thickening and arterial intimal fibrosis are prominent histologic features of vessels affected by major lower extremity trauma.

Implementing an orthoplastic treatment protocol for open tibia fractures reduces complication rates in tertiary trauma unit.

INTRODUCTION: Open tibia fracture (OTF) causes a considerable increase in morbidity and risk for complications compared to closed fractures. The most significant OTF complication leading to morbidity is commonly considered to be fracture-related infection (FRI). In September 2016, Tampere University Hospital (TAUH) introduced a treatment protocol for OTFs based on the BOAST 4 guideline. The aim of this study is to investigate the outcomes before and after implementation of the OTF treatment protocol. MATERIALS AND METHODS: A retrospective cohort study was conducted using handpicked data from the patient record databases of TAUH from May 1, 2007, to May 10, 2021. For patients with OTF, we collected descriptive information, known risk factors for FRI and nonunion, bony fixation method, possible soft tissue reconstruction method, information about the timing of internal fixation and soft tissue coverage, and timing of primary operation. As outcome measures, we collected information on FRI, reoperation due to non-union, flap failure, and secondary amputation. We then compared the incidence of complications before and after the implementation of the OTF treatment protocol at TAUH. RESULTS: After predefined exclusions, a total of 203 patients with OTF were included. Of these, 141 were treated before and 62 after the implementation of the OTF treatment protocol. The FRI rate in the pre-protocol group was significantly higher compared to the protocol group (20.6% vs 1.6%, p = 0.0015). The incidence of reoperation due to nonunion was also significantly higher in the pre-protocol group (27.7% vs 9.7%, p = 0.0054). According to multivariable analysis, definitive fixation and soft tissue coverage performed in separate operations was an independent risk factor for both FRI and reoperation due to nonunion. CONCLUSIONS: After implementation, the BOAST 4 based OTF treatment protocol reduced the rate of FRI and reoperation due to nonunion in patients with OTF treated at TAUH during the study period. We, therefore, recommend the implementation of such a treatment protocol in all major trauma centers treating patients with OTF. Furthermore, we also recommend the immediate referral of patients with complex OTF from hospitals lacking the preconditions to provide BOAST 4 based treatment to specialized centers.

Quality registry improves the data of chronic ulcers: Validation of Tampere Wound Registry.

Quality registries are potential tools for improving health care documentation, but the quality and completeness of each registry should be ensured. This study aimed to evaluate the completion rate (completeness) and accuracy of data, first contact-to-registration time (timeliness), and case coverage of the Tampere Wound Registry (TWR) to assess whether it can be reliably used in clinical practice and for research purposes. Data from all 923 patients registered in the TWR between 5 June 2018 and 31 December 2020 were included in the analysis of data completeness, while data accuracy, timeliness and case coverage were analysed in those registered during the year 2020. In all analyses values over 80% were considered good and values over 90% excellent. The study showed that the overall completeness of the TWR was 81% and overall accuracy was 93%. Timeliness achieved 86% within the first 24 h, and case coverage was found to be 91%. When completion of seven selected variables was compared between TWR and patient medical records, the TWR was found to be more complete in five out of seven variables. In conclusion, the TWR proved to be a reliable tool for health care documentation and an even more reliable data source than patient medical records.

Phase 1 Lymfactin® Study: 24-month Efficacy and Safety Results of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema.

BACKGROUND: Lymphedema is a common problem after breast cancer treatment. Lymfactin® is a prolymphangiogenic growth factor vector inducing the expression of human vascular endothelial growth factor C (VEGF-C). It promotes growth and repair of lymphatic vessels. METHODS: Lymfactin® was combined with microvascular lymph node transfer surgery (VLNT) to study the safety and efficacy of the treatment in breast cancer-related upper limb lymphedema (BCRL) patients. This is a continuation study with a 3 year efficacy and 5 year safety follow-up. RESULTS: Fifteen patients were recruited in the study between June 2016 and February 2018. Three patients received a lower dose (1 × 1010 viral particles (vp)), and 12 patients received a higher dose (1 × 1011 vp) of Lymfactin®, respectively. In the higher dose group, the reduction of excess arm volume was on average 46% after the 12 month follow-up, and the transport index was improved in 7/12 patients. At baseline, removal of the compression garment for 7 days resulted in significant arm swelling (105.7±161.0 ml, p=0.0253). However, at 12 months, there was less and not significant swelling after removal of the garment (84.4±143.0 ml, p=0.0682). Lymphedema Quality of Life Inventory (LQOLI or LyQLI) questionnaire showed significant and sustained improvement of quality of life. CONCLUSIONS: During 24 months' of follow-up, the results indicate that Lymfactin® is well tolerated. The most promising findings were a 46% reduction in excess arm volume and a nonsignificant volume increase after garment removal at 12 months, suggesting that there is potential for the reduction of lymphedema.

Surgical and patient-reported outcomes after total knee arthroplasty requiring soft tissue flap reconstruction - A 12-year experience from high-volume arthroplasty hospital.

BACKGROUND: This study investigates the outcomes of complex knee joint reconstructions performed by an orthoplastic surgery team at a tertiary referral hospital. METHODS: Retrospective review of all the total knee arthroplasty (TKA)/revision TKA (rTKA) procedures with soft tissue flap reconstruction performed between 2008 and 2019 was conducted. Patients were stratified into two groups according to the urgency of surgery: scheduled non-complicated (SNC) and emergent complicated (EC). The whole study cohort was also categorized into non-infected and infected groups. RESULTS: Of 20,184 TKAs operated, 58 patients required flap reconstruction (SNC group n = 27; EC group n = 31). The most common reconstruction was medial gastrocnemius flap (74%). Mean follow-up time was 31.9 months. Functional knee joint salvage was achieved in 96.3% the SNC group and in 80.6% the EC group patients (p = 0.07). Transfemoral amputation rates were 3.7% in the SNC group vs. 6.5% in the EC group (p = 0.36). Oxford Knee Score was 34.5 vs. 25.5 (p = 0.21), and range of motion was 100° vs. 93° (p = 0.37) in the SNC and EC groups, respectively. Superior functional knee joint salvage rates were achieved in the non-infected group compared to the infected group (97.1% vs. 75.0%, p = 0.004). However, the transfemoral amputation rate was nearly three-fold in the infected group (8.3% vs. 2.9%, p = 0.36). Estimated five-year survival with functional knee joint was higher in the non-infected group (p = 0.03). CONCLUSIONS: Both the SNC and EC groups had similar acceptable limb salvage rates, and functional and PROM outcomes. Infection reduces the probability of a functional knee joint after TKA and flap reconstruction.

ESPRAS Survey on Continuing Education in Plastic, Reconstructive and Aesthetic Surgery in Europe.

BACKGROUND: Specialty training in plastic, reconstructive and aesthetic surgery is a prerequisite for safe and effective provision of care. The aim of this study was to assess and portray similarities and differences in the continuing education and specialization in plastic surgery in Europe. MATERIAL AND METHODS: A detailed questionnaire was designed and distributed utilizing an online survey administration software. Questions addressed core items regarding continuing education and specialization in plastic surgery in Europe. Participants were addressed directly via the European Leadership Forum (ELF) of the European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS). All participants had detailed knowledge of the organization and management of plastic surgical training in their respective country. RESULTS: The survey was completed by 29 participants from 23 European countries. During specialization, plastic surgeons in Europe are trained in advanced tissue transfer and repair and aesthetic principles in all parts of the human body and within several subspecialties. Moreover, rotations in intensive as well as emergency care are compulsory in most European countries. Board certification is only provided for surgeons who have had multiple years of training regulated by a national board, who provide evidence of individually performed operative procedures in several anatomical regions and subspecialties, and who pass a final oral and/or written examination. CONCLUSION: Board certified plastic surgeons meet the highest degree of qualification, are trained in all parts of the body and in the management of complications. The standard of continuing education and qualification of European plastic surgeons is high, providing an excellent level of plastic surgical care throughout Europe. HINTERGRUND: Die Facharzt-Weiterbildung für Plastische und Ästhetische Chirurgie ist eine Grundvoraussetzung für sichere und effektive Patientenversorgung. Ziel der vorliegenden Studie war die Darstellung von Gemeinsamkeiten und Unterschieden in der Weiterbildung für Plastische Chirurgie innerhalb von Europa. MATERIALIEN UND METHODEN: Ein internetbasierter Fragebogen wurde mit Hilfe eines kostenlosen Formularerstellungstools erstellt und verteilt. Die Fragen betrafen Kernpunkte der Weiterbildung für Plastische Chirurgie in Europa. Die Teilnehmer wurden direkt über das European Leadership Forum (ELF) der European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS) kontaktiert. Alle Teilnehmer hatten weitreichende Kenntnisse über die Organisation und Struktur der plastisch-chirurgischen Weiterbildung in ihrem jeweiligen Land. ERGEBNISSE: 29 Teilnehmer*innen aus 23 europäischen Ländern nahmen an der Umfrage teil. Die Weiterbildung für Plastische Chirurgie beinhaltet grundlegende Prinzipien und Techniken zur Wiederherstellung von Form und Funktion innerhalb der verschiedenen Säulen der Plastischen Chirurgie, sowie in allen Körperregionen. In den meisten europäischen Ländern ist eine Rotation in der Intensiv- und Notfallmedizin und die Behandlung kritisch kranker Patienten obligatorisch. Voraussetzung für die Facharztbezeichnung ist die mehrjährige, national organisierte Weiterbildung, der Nachweis einer festgelegten Anzahl selbstständig durchgeführter Operationen, sowie die mündliche und/oder schriftliche Abschlussprüfung. SCHLUSSFOLGERUNG: Fachärzte für Plastische und Ästhetische Chirurgie sind hochqualifiziert und auch im Umgang mit Komplikationen geschult. Der Standard der Weiterbildung der europäischen Plastischen Chirurgen ist hoch, so dass innerhalb Europas eine hohe Qualität plastisch-chirurgischer Versorgung gewährleistet ist.

Adipose tissue as a source of growth factors to promote wound healing: a human study of skin graft donor sites.

OBJECTIVE: In the microenvironment of wound sites, naturally occurring growth factors are crucial for cell migration, opsonisation, chemotaxis, differentiation and angiogenesis. Exogenous growth factors, such as platelet-rich plasma (PRP) and adipose tissue, also improve healing. METHOD: In the present within-subject study, we described the effects of PRP and adipose tissue extract (ATE) on skin graft donor site wound healing in patients requiring split-thickness skin grafts. Each patient, having at least two donor sites, received both control (no growth factor) and experimental (PRP or ATE) treatments. Wounds were evaluated on days 5, 7, 10, 15, 30 and 60. Digital photography and spectral images were used to analyse haemoglobin and melanin content, and re-epithelialisation area. Pain was assessed by visual analogue scale. Scar characteristics were scored on days 30 and 60. Biomaterial samples were analysed for growth factor and protein content. RESULTS: The study included 24 patients (18 male and six female; mean age: 59.1 years). PRP was topically applied to wounds in 11 patients (13 donor sites) and ATE in 13 patients (15 sites). ATE-treated donor sites exhibited significantly accelerated wound re-epithelialisation on days 5 and 7 compared with control sites (p=0.003 and 0.04, respectively). PRP accelerated healing on day 7 compared with control sites (p=0.001). Additionally, the application of ATE improved scar quality on days 30 and 60 (p=0.0005 and 0.02, respectively). Pain scores did not differ significantly between treatments. CONCLUSION: In this study, both growth factor sources stimulated wound healing. ATE is an alternative source of growth factors that promote early wound healing and improve scar quality.

The Development of Lower Limb Amputations in Finland from 1997 to 2018: A Nationwide Retrospective Registry Study.

OBJECTIVE: To investigate the rates of transfemoral, transtibial foot and toe amputations, and lower limb revascularisations in Finland between 1997 and 2018. METHODS: Retrospective observational cohort study. Data from the Finnish National Hospital Discharge Register for the period 1997 - 2018 were used. The study population covered all patients 20 years and older who underwent lower limb revascularisations or amputations in private and public hospitals during the study period. All (outpatient and inpatient) amputations and revascularisations were included. The age adjusted incidence rates were based on the annual mid populations, which were obtained from the Official Statistics of Finland. Continuous variables were presented as median with interquartile range (IQR) or as mean with standard deviation. The 95% confidence intervals (CI) for the incidence rates were calculated using the Poisson exact method. All changes in incidence were calculated as relative change (%). RESULTS: A total of 75 230 patients underwent 149 492 lower limb revascularisations and amputations between 1997 and 2018 in Finland. The median (IQR) age of the patients was 73 (65, 80) and 60% of the patients were men. The incidence of all endovascular lower limb revascularisations increased by 159% while the incidence of lower limb amputations increased by 25%. The most notable increase occurred in toe (84%) and foot (107%) amputations, while the incidence of transfemoral amputations remained steady and transtibial amputations decreased by 53%. The first minor-major amputation ratio (CI) increased from 1.13 (1.03 - 1.24) to 1.49 (1.36 to 1.62) during the study period. CONCLUSION: The findings of this nationwide cohort study suggest that the incidence of both lower limb revascularisations and amputations is increasing. More specifically, revascularisations are more often performed endovascularly, and the incidence of transtibial amputations is declining, whereas the incidence of toe and foot amputations is increasing.

Major Amputation Profoundly Increases Mortality in Patients With Diabetic Foot Infection.

Introduction: An acute diabetic foot infection (DFI) is a serious condition and a leading cause of hospitalization and major amputation in patients with diabetes. Aim of this study was to evaluate the long term survival and risk factors for death and amputation after the DFI requiring hospital treatment. Materials and Methods: A retrospective study included all adult patients hospitalized for DFI treatments during 2010-2014. Overall survival (OS) and amputation free survival (AFS) (without major amputation) was calculated. We performed a Cox regression analysis of several clinical parameters to evaluate the effects of clinical parameters on overall and amputation-free survival. Results: Total of 324 patients with mean age of 66.8 (SD 12.8) years were included. The one- and five-year OS after DFI 81.2% (95%CI 77.5-84.9%) and 49.7% (95%CI 44.8-54.6%), respectively. Major amputation, wound ischemia, older age, and a low glomerular filtration rate reduced the OS after DFI. After a major amputation, the one- and five-year OS was 41.7% (95%CI 13.9-69.5) and 8.3% (95%CI 0.0-24.0%), respectively. Wound ischemia, older age, and elevated C-reactive protein reduced AFS. In contrast, hypertensive medication use was identified as a protective factor. Conclusion: Mortality after a DFI remains high and is significantly increased after a major amputation. Findings highlight the importance of early wound and ischemia management for DFI prevention.

Pathogens Causing Diabetic Foot Infection and the Reliability of the Superficial Culture.

Background: Diabetic foot infection (DFI) is a severe complication of diabetes and a leading cause of hospitalization in the population with diabetes. Empirical intravenous antibiotic agents are initiated according to guidelines based on previously published data on typical pathogens. Therefore, regular evaluation of the pathogens in DFI and their resistance is important to validate current therapies. We evaluated the most current data on bacterial cultures in patients treated at our hospital for DFI and the resistance to the most common antibiotic agents, as well as the reliability of superficial cultures compared with deep tissue cultures. Patients and Methods: This retrospective study was performed at the University Hospital of Tampere and comprised 325 patients with 405 hospitalizations for DFI during the years 2010-2014. Results: The most frequent pathogens in superficial and deep samples were Staphylococcus aureus (36.9%), gram-negative bacilli (24.6%), and ß-hemolytic streptococci (BHS, 19.5%). Septicemia was caused most often by Staphylococcus aureus and BHS (34.6% each). The specificity of superficial culture was 91.8%-92.8% and sensitivity 66.7%-87.5%. Conclusions: This study indicates the need to cover Staphylococcus aureus, BHS, and gram-negative bacilli when treating DFI. The reliability of superficial culture was surprisingly good.

Phase 1 LymfactinⓇ Study: Short-term Safety of Combined Adenoviral VEGF-C and Lymph Node Transfer Treatment for Upper Extremity Lymphedema.

OBJECTIVE: To study the safety and tolerability of LymfactinⓇ treatment combined with microvascular lymph node transfer surgery in patients with upper limb lymphedema. BACKGROUND: Upper limb lymphedema is a common clinical challenge after breast cancer surgery and/or radiotherapy. LymfactinⓇ is an adenovirus type 5-based gene therapy involving expression of human vascular endothelial growth factor C (VEGF-C) in the damaged tissue. It aims to correct deficient lymphatic flow by promoting the growth and repair of lymphatic vessels. METHODS: In Phase I, LymfactinⓇ was combined with microvascular lymph node transfer surgery to study the safety and tolerability of LymfactinⓇ and the biodistribution of the viral vector in patients with upper limb lymphedema. RESULTS: Fifteen patients with breast cancer-associated secondary lymphedema of the upper arm were recruited between December 2016 and February 2018. Three patients received a lower dose (1 × 1010) and 12 a higher dose (1 × 1011) of viral particles, respectively. No dose-limiting toxicities were observed, and the study was completed with the pre-determined maximum dose. Commonly reported adverse events during the 12-month follow-up were common cold, fever, gastroenteritis, pain in the operation area, headache, muscle ache and elevated liver enzymes. Serious adverse events consisted of two erysipelas infections in the lymphedema arm (requiring hospitalization) and one hematoma of the flap donor site. CONCLUSIONS: After 12 months' follow-up, results indicate that LymfactinⓇ is well tolerated. The study continues with a 36-months efficacy and 5 years safety follow-up of the patients. The oncological safety aspects of LymfactinⓇ will require a longer follow-up period.

Surgical and oncological outcomes after hindquarter amputation for pelvic sarcoma.

AIMS: Survival rates and local control after resection of a sarcoma of the pelvis compare poorly to those of the limbs and have a high incidence of complications. The outcome for patients who need a hindquarter amputation (HQA) to treat a pelvic sarcoma is poor. Our aim was to evaluate the patient, tumour, and reconstructive factors that affect the survival of the patients who undergo HQA for primary or recurrent pelvic sarcoma. METHODS: We carried out a retrospective review of all sarcoma patients who had undergone a HQA in a supraregional sarcoma unit between 1996 and 2018. Outcomes included oncological, surgical, and survival characteristics. RESULTS: A total of 136 patients, with a mean age of 51 (12 to 83) underwent HQA, 91 for a bone sarcoma and 45 for a soft tissue sarcoma. The overall survival (OS) after primary HQA for a bone sarcoma was 90.7 months (95% confidence interval (CI) 64.1 to 117.2). In patients undergoing a secondary salvage HQA it was 90.3 months (95% CI 58.1 to 122.5) (p = 0.727). For those treated for a soft tissue sarcoma (STS), the mean OS was 59.3 months (95% CI 31.1 to 88.6) for patients with a primary HQA, and 12.5 months (95% CI 9.4 to 15.5) for those undergoing a secondary salvage HQA (p = 0.038). On multivariate analysis, high histological grade (hazard ratio (HR) 2.033, 95% CI 1.127 to 3.676; p = 0.018) and a diagnosis of STS (HR 1.653, 95% CI 1.027 to 2.660; p = 0.039) were associated with a poor prognosis. The 30-day mortality for patients with curative intent was 0.8% (1/128). For those in whom surgery was carried out with palliative intent it was 33.3% (2/6) (p = 0.001). In total, 53.7% (n = 73) of patients had at least one complication with 23.5% (n = 32) requiring at least one further operation. Direct closure was inferior to flap reconstruction in terms of complete primary wound healing (60.0% (3/5) vs 82.0% (82/100); p = 0.023). CONCLUSION: In carefully selected patients HQA is associated with satisfactory overall survival, with a low risk of perioperative mortality, but considerable morbidity. However, caution must be exercised when considering the procedure for palliation due to the high incidence of early postoperative mortality. Cite this article: Bone Joint J 2020;102-B(6):788-794.

Histopathology and immunohistochemical analysis of 5-fluorouracil and triamcinolone treated keloids in double-blinded randomized controlled trial.

Keloids are a major complication related to surgical wound healing and very challenging condition to treat. Many treatment options are available, but the efficacy of the treatment is poor in most of cases and some keloids do not respond to the treatment at all. We compared the efficacy of intralesional 5-fluorouracil (5-FU) and triamcinolone (TAC) injections in a double-blind randomized controlled trial (RCT). Forty-three patients with 50 keloid scars were treated with either intralesional TAC or 5-FU-injections over 6 months. We wanted to find out whether biological features (cell density, cell proliferation rate, vascular density, myofibroblast numbers, steroid hormone receptor expression) in keloids could be used to predict the response to therapy and define the biological changes that take place in patients receiving a response. As there was no statistically significant difference in the remission rate between TAC and 5-FU treatments, all patients were combined and analyzed as responders and nonresponders. Although responders have slightly more myofibroblasts than the nonresponders in their keloids in the pretreatment biopsy samples, we could not identify a single predictive factor that could identify those patients that respond to drug injections. The good clinical response to therapy is associated with the simultaneous reduction of myofibroblasts in the keloid. This study demonstrates that myofibroblasts are reduced in number in those keloids that were responsive to therapy, and that both 5-FU and TAC injections are useful for keloid treatment.

Transverse myocutaneous gracilis flap reconstruction is feasible after pelvic exenteration: 12-year surgical and oncological results.

INTRODUCTION: Pelvic exenteration (PE) is the only curative treatment for certain locally advanced intrapelvic malignancies. PE has high morbidity, and optimal reconstruction of the pelvic floor remains undetermined. MATERIALS AND METHODS: A retrospective chart review was performed at a tertiary university center to assess the surgical and oncological outcomes of 39 PE procedures over a 12-year period. The majority of patients (n = 25) underwent transverse musculocutaneous gracilis (TMG) flap reconstruction for pelvic floor reconstruction. RESULTS: The 1- and 5-year overall survival (OS) was 72% (95%CI 58%-86%) and 48% (95%CI 31%-65%), respectively. In multivariate analysis, lymph node metastasis (HR 3.070, p = 0.024) and positive surgical margins (HR 3.928, p = 0.009) were risk factors for OS. In this population, 71.8% of the patients had at least one complication. The complication rate was 65.4% and 84.6% for patients with versus without flap reconstruction, respectively (p = 0.191). The length of stay was longer for patients with a major complication 16,0 ±â€¯5,9 days vs. 29,4 ±â€¯14,8 days, p = 0,001, but complications did not affect OS. CONCLUSION: For selected patients, PE is a curative option for locally advanced, residual, or recurrent intrapelvic tumors. Pelvic floor and vulvovaginal defects can reliably be reconstructed using TMG flaps. TMG flaps are favored in our institution over abdominal-based flaps because the donor site morbidity is reasonable and TMG does not interfere with enterostomy.

Clinical results and quality of life after reconstruction following sacrectomy for primary bone malignancy.

BACKGROUND: Sacrectomy is a rare and demanding surgical procedure that results in major soft tissue defects and spinopelvic discontinuity. No consensus is available on the optimal reconstruction algorithm. Therefore, the present study evaluated the results of sacrectomy reconstruction and its impact on patients' quality of life (QOL). METHODS: A retrospective chart review was conducted for 21 patients who underwent sacrectomy for a primary bone tumour. Patients were divided into groups based on the timing of reconstruction as follows: no reconstruction, immediate reconstruction or delayed reconstruction. QOL was measured using the EQ-5D instrument before and after surgery in patients treated in the intensive care unit. RESULTS: The mean patient age was 57 (range 22-81) years. The most common reconstruction was gluteal muscle flap (n = 9) and gluteal fasciocutaneous flap (n = 4). Four patients required free-tissue transfer, three latissimus dorsi flaps and one vascular fibula bone transfer. No free flap losses were noted. The need for unplanned re-operations did not differ between groups (p = 0.397), and no significant differences were found for pre- and post-operative QOL or any of its dimensions. DISCUSSION: Free flap surgery is reliable for reconstructing the largest sacrectomy defects. Even in the most complex cases, surgery can be safely staged, and final reconstruction can be carried out within 1 week of resection surgery without increasing peri­operative complications. Sacrectomy does not have an immoderate effect on the measured QOL.

Adipose tissue extract shows potential for wound healing: in vitro proliferation and migration of cell types contributing to wound healing in the presence of adipose tissue preparation and platelet rich plasma.

Growth factors are the key elements in wound healing signaling for cell migration, differentiation and proliferation. Platelet-rich plasma (PRP), one of the most studied sources of growth factors, has demonstrated to promote wound healing in vitro and in vivo. Adipose tissue is an alternative source of growth factors. Through a simple lipoaspirate method, adipose derived growth factor-rich preparation (adipose tissue extract; ATE) can be obtained. The authors set out to compare the effects of these two growth factor sources in cell proliferation and migration (scratch) assays of keratinocyte, fibroblast, endothelial and adipose derived stem cells. Growth factors involved in wound healing were measured: keratinocyte growth factor, epidermal growth factor, insulin-like growth factor, interleukin 6, platelet-derived growth factor beta, tumor necrosis factor alfa, transforming growth factor beta and vascular endothelial growth factor. PRP showed higher growth factor concentrations, except for keratinocyte growth factor, that was present in adipose tissue in greater quantities. This was reflected in vitro, where ATE significantly induced proliferation of keratinocytes at day 6 (p < 0.001), compared to plasma and control. Similarly, ATE-treated fibroblast and adipose stem cell cultures showed accelerated migration in scratch assays. Moreover, both sources showed accelerated keratinocyte migration. Adipose tissue preparation has an inductive effect in wound healing by proliferation and migration of cells involved in wound closure. Adipose tissue preparation appears to offer the distinct advantage of containing the adequate quantities of growth factors that induce cell activation, proliferation and migration, particularly in the early phase of wound healing.