A novel surgical risk predictor combining frailty and hypoalbuminemia - A cohort study of 9.8m patients from the ACS-NSQIP database.

INTRODUCTION: The functional decline seen in frail patients is associated with significant morbidity and mortality. The modified frailty index 5 (mFI-5) score is an accepted risk predictor score in surgery. Hypoalbuminemia has been correlated with poor postoperative outcomes.There exists, however, a gap in the literature regarding the combined assessment of frailty and hypoalbuminemia and the predictive power of this combined assessment. This retrospective cohort study aimed to investigate the association of preoperative albumin and frailty, as assessed with the mFI-5 score, and its ability to predict surgical outcomes. METHODS: We queried the ACS-NSQIP database (2008-2021) to identify all surgical patients. Perioperative data, including demographics and preoperative laboratory values, including albumin, were collected. The predictive power of the mFI-5 and hypoalbuminemia (Alb) independently, and in combination (mFI-5+Alb), was assessed using multivariable linear and logistic regression models 30-day outcomes were assessed including mortality, length of hospital stay, reoperation, medical and surgical complications, and discharge destination. RESULTS: A total of 9,782,973 patients were identified of whom 4,927,520 (50.4%) were non-frail (mFI=0), 3,266,636 had a frailty score of 1 (33.4%), 1,373,968 a score of 2 (14.0%), 188,821 a score of 3 (1.9%) and 26,006 a score greater or equal to 4 (0.3%). Albumin levels were available for 4,570,473 patients (46.7%), of whom 848,315 (18.6%) had hypoalbuminemia. The combined assessment (mFI-5+Alb) was found to be a more accurate risk predictor than each factor independently for all outcomes. A weak negative correlation between serum albumin levels and mFI scores was established (Spearman R: -0.2; <0.0001). CONCLUSIONS: Combined assessment of frailty and albumin was the strongest risk predictor. Therefore, for patients undergoing surgery, we recommend consideration of both serum albumin and frailty in order to optimally determine perioperative planning, including multi-disciplinary care mobilization and pre- and posthabilitation.

A single-center retrospective comparison of muscle versus cutaneous free flaps for posterior elbow defect reconstruction.

INTRODUCTION: Comparative data on free flap outcomes for elbow defect reconstruction are still lacking. This study aimed to compare complication rates of free muscle flaps (MFs) versus cutaneous flaps (CFs) for posterior elbow reconstruction. METHODS: In a single-center retrospective analysis, patients who underwent posterior elbow reconstruction with free MFs and CFs from 2000 to 2021 were analyzed. Retrospective chart review included patient demographics, operative details, and post-operative complications. Outcomes of interest that were compared included microvascular complications, partial or total flap necroses, wound dehiscence, hematoma or flap infection, and donor-site complications. RESULTS: Sixty-six free flaps (CFs: n = 42; MFs: n = 24) were included, with a trend over time toward using CFs (64%). MFs were used for larger defects (CF: 175 ± 82 vs. MF: 212 ± 146 cm2; p = 0.13). Outcome analysis revealed an equal distribution of microvascular complications (10% vs. 13%; p = 0.7), partial flap necrosis (7% vs. 8%; p > 0.9), wound dehiscence (7% vs. 4%; p > 0.9), evacuation of hematoma (10% vs. 4%; p = 0.7), and infection (0% vs. 4%; p = 0.4). Total flap necrosis requiring additional flap surgery was necessary in one CF (2%) and in no MF (0%) (p > 0.9). CONCLUSION: Surgical outcomes, flap necrosis rates, and microsurgical complications did not differ between CFs and MFs. Both flap types are safe and effective options. The free anterolateral thigh and latissimus dorsi flaps represent indispensable workhorses for the reconstruction of extensive elbow defects.

C-reactive protein orchestrates acute allograft rejection in vascularized composite allotransplantation via selective activation of monocyte subsets.

INTRODUCTION: Despite advancements in transplant immunology and vascularized composite allotransplantation (VCA), the longevity of allografts remains hindered by the challenge of allograft rejection. The acute-phase response, an immune-inflammatory reaction to ischemia/reperfusion that occurs directly after allogeneic transplantation, serves as a catalyst for graft rejection. This immune response is orchestrated by acute-phase reactants through intricate crosstalk with the mononuclear phagocyte system. OBJECTIVE: C-reactive protein (CRP), a well-known marker of inflammation, possesses pro-inflammatory properties and exacerbates ischemia/reperfusion injury. Thus, we investigated how CRP impacts acute allograft rejection. METHODS: Prompted by clinical observations in facial VCAs, we employed a complex hindlimb transplantation model in rats to investigate the direct impact of CRP on transplant rejection. RESULTS: Our findings demonstrate that CRP expedites allograft rejection and diminishes allograft survival by selectively activating non-classical monocytes. Therapeutic stabilization of CRP abrogates this activating effect on monocytes, thereby attenuating acute allograft rejection. Intravital imagining of graft-infiltrating, recipient-derived monocytes during the early phase of acute rejection corroborated their differential regulation by CRP and their pivotal role in driving the initial stages of graft rejection. CONCLUSION: The differential activation of recipient-derived monocytes by CRP exacerbates the innate immune response and accelerates clinical allograft rejection. Thus, therapeutic targeting of CRP represents a novel and promising strategy for preventing acute allograft rejection and potentially mitigating chronic allograft rejection.

A nomogram for predicting outcomes following pedicled flap reconstruction of the lower extremity.

INTRODUCTION: Lower extremity reconstructions with soft tissue flaps account for a significant proportion of reconstructive surgery. Pedicled flaps are a procedure of choice, particularly in multimorbid patients and those with small to medium-sized defects. Complication rates are high and should not be underestimated, with accurate preoperative risk factor assessment being imperative. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program Database (2008-2021), we analyzed all patients who underwent pedicled flap reconstruction of the lower extremity. Demographic data, comorbidities, and perioperative data were extracted. We identified risk factors of major surgical complications within 30 days of surgery through uni- and multivariate regression analyses. On this basis, a nomogram for predicting the risk of complications was developed to allow for feasible point-of-care risk assessment. RESULTS: A total of 6475 adult patients were identified. The most common comorbidities were hypertension (n = 3363, 51.9%) and obesity (n = 2306, 35.6%) and most common American Society of Anesthesiologists (ASA) class was class 3 (n = 3703, 57.2%). The most common complication was bleeding/transfusion (n = 1293, 19.9%). Multivariate regression revealed longer procedures, inpatient setting, higher ASA scores, hypertension, and procedures performed by orthopedic and vascular surgeons as predictors for higher risk of post-operative complications. CONCLUSION: Leveraging a risk- and case-mix-adjusted multi-institutional database, a nomogram for post-operative surgical complications within 30 days after pedicled flap reconstruction in the lower extremity was developed. This broadly applicable risk prediction tool can aid in decision-making when assessing patient eligibility.

Robot-assisted Microsurgery: Lessons Learned from 50 Consecutive Cases.

Background: The potential of robot-assisted surgery in plastic and reconstructive surgery remains to be established, especially in free tissue transfer. This prospective study aimed to present our experience and findings from the first 50 consecutive cases of robot-assisted microsurgery using the Symani surgical system. Methods: A prospective database was maintained, recording patient demographics and surgical details for all cases of robot-assisted microsurgery in a large academic institution. All surgeons underwent an intensive training program with the Symani surgical system. Results: A total of 50 patients who underwent robot-assisted microsurgical reconstruction were identified. Free microsurgical tissue transfer was performed in 45 cases, targeted muscle reinnervation in four cases, and lymphovenous anastomoses in a single case. A total of 94 robot-assisted anastomoses and coaptations were performed, (46 venous and 30 arterial anastomoses, 16 nerve coaptations, two lymphovenous anastomoses). Six cases involved perforator-to-perforator anastomoses. Ninety-eight percent of attempted anastomoses were completed using the robot. Size-mismatch anastomoses, seen in 37.8% of cases, took significantly longer. Minor complications occurred in three cases and major in six cases. There were three cases of microvascular compromise requiring revision. One partial flap loss and no complete flap loss occurred. Conclusions: Our study highlights the immense potential of robot-assisted microsurgery, and a feasible and effective modality for various microsurgical procedures, with outcomes comparable to those of conventional microsurgery. Despite challenges, such as increased operating times and higher costs, the technology offers significant advantages, such as enhanced precision and motion scaling. We identify a slow learning curve and a necessity for higher caseloads.

The free vastus lateralis-And conjoined vastus lateralis anterolateral thigh/tensor fascia lata flap for oncological chest wall reconstruction.

INTRODUCTION: A reconstructive option for extensive chest wall reconstruction is the free myocutaneous vastus lateralis muscle (VL) flap which can be performed in isolation or in conjunction with a fasciocutaneus anterolateral thigh (cVLALT) and/or myofasciocutaneous tensor fascia lata flap (cVLTFL). We aimed to directly compare the outcomes of these reconstructive options. METHODS: Patients who underwent oncological chest wall reconstruction with a free VL, cVLALT, or cVLTFL flap between February 2010 and 2022 were included in this retrospective study. Patient demographics, surgical characteristics, as well as medical and reconstructive outcomes, were evaluated. The operative outcomes between myocutaneous VL, cVLALT, and cVLTFL flap reconstructions were compared. RESULTS: A total of 41 patients underwent chest wall reconstruction with a free myocutaneous VL (n = 25; 61%), cVLALT (n = 14; 34%), or cVLTFL Three acute flap thromboses occurred in the entire cohort (3/41, 7%), with one myocutaneous VL flap failing because of recurrent venous thrombosis during the salvage procedure. Total flap necrosis was seen in two cases (5%; VL flap: n = 1; cVLALT flap: n = 1), and partial flap necrosis in one VL flap (1/25, 4%) and in the distal ALT portion of three cVLALT flaps (3/14, 21%). No significant difference was seen between isolated VL and conjoined VL flaps regarding the partial (p = .28) or total flap necrosis rate (p = .9). CONCLUSION: The free (conjoined) VL flap provides reliable outcomes for obliterating dead space achieving durable reconstruction of complex chest wall defects.

A new surgical concept for the efficient treatment of large and deep burns.

Effective burn surgery is based on two fundamental principles: prompt excision of necrotic tissue and definitive coverage preserving functional dermis and body contour. There is often compromise, either prioritizing the urgency of excision or opting for patient stability and optimal conditions prior to autografting. We propose a surgical concept that addresses this critical treatment gap. In 2022 we implemented a new three-phase protocol, EDM: (Excision phase, E) Immediate excision of the burn wound preserving body contour; (Dermis phase, D) definitive temporization of the wound bed, using Biodegradable Temporizing Matrix (BTM), to prepare it for successful grafting. (Meek phase, M): Upon complete dermal temporization, full autologous coverage in a single micrografting procedure. We performed a retrospective single-center cohort study to characterize the EDM protocol compared to the prior standard of care (>40%TBSA, n=5 in EDM vs. n=10 matched controls). Primary outcomes were total surgeries required, total surgeries to achieve>90% healing, uninterrupted recovery time without surgery, and time on mechanical ventilation. The EDM group required fewer surgeries in total (5 vs. 9.5 ; p=0.01) and to achieve>90% healing (3 vs. 6.5; p=0.001). EDM patients experienced longer uninterrupted recovery (24 vs. 14 days, p=0.001). Additionally, EDM patients spent less time on mechanical ventilation (210 vs. 1136 hours, p=0.005). The EDM protocol could improve surgical efficiency, ultimately having the potential to expedite rehabilitation in severely burned patients. The study underscores the potential of combining fundamentals of burn surgery, with innovative surgical techniques and materials, in order to bridge the gap between excision and grafting.

The Epidemiology and Outcomes of Perineal and Genital Burn Injury in Low- and Middle- Income Countries: A Global Burn Registry Study.

INTRODUCTION: The epidemiology, care, and outcomes of perineal and genital burns (PG) in high-income countries have been previously described, but an analysis of this topic in LMICs has yet to be performed. We use the World Health Organization's Global Burn Registry to fill this gap. METHODS: The GBR was searched from inception to November 2023 to identify all burn patients, excluding cases from high-income countries. Demographics and mechanism of injury were retrieved. Primary outcomes were length of hospital stay (LOHS), surgical intervention, discharge with physical impairment, and mortality. A multivariate regression analysis was performed controlling for burnt total body surface area (TBSA), age, sex, inhalation injury, mechanism of burn and care center characteristics. RESULTS: Of 9041 patients identified, 1213 (13.4 %) had PG burns with 136 (1.6 %) isolated to the PG region. PG patients had higher TBSA (p < 0.001) and more inhalation injury (p < 0.001). They had better access to rehabilitation and lower access to theater space for burns (p < 0.001). Multivariable analysis showed that PG patients had longer LOHS (p = 0.001), greater mortality (p < 0.001), were less likely to undergo surgery (p = 0.01) or be discharged home with physical impairment (p = 0.03). CONCLUSION: Similarities and differences exist between high- and low/middle-income countries in terms of the patterns of injury, care, and recovery in patients with PG burns. The longer LOHS and higher mortality among PG patients, previously reported in high-income countries, are verified. This highlights the importance of greater vigilance when caring for such patients.

Quality of life and satisfaction after breast augmentation: A systematic review and meta-analysis of Breast-Q patient-reported outcomes.

BACKGROUND: Breast augmentation ranks among the most popular plastic surgery procedures. Yet, reports on post-operative patient-reported quality of life (QoL) and satisfaction remain conflicting. METHODS: A systematic review was conducted following the PRISMA guidelines. Three databases were searched for eligible studies that reported pre-and/or post-operative Breast-Q™ augmentation scores for patient QoL (psychosocial, sexual, and physical well-being) and/or satisfaction. RESULTS: A total of 39 studies (53 patient cohorts and 18,322 patients) were included in the quantitative synthesis. The pairwise meta-analysis revealed significant improvements in patient-reported psychosocial (MD: +38.10) and sexual well-being (MD: +40.20) as well as satisfaction with breast (MD: +47.88) (all p < 0.00001). Physical well-being improved slightly after breast augmentation (MD: +6.97; p = 0.42). The single-arm meta-analysis yielded comparable results, with Breast-Q™ scores in psychosocial and sexual well-being as well as satisfaction with breast increasing from 37.2, 31.1, and 26.3 to 75.0, 70.6, and 72.7, respectively (all p < 0.00001). Physical well-being improved by 8.1 (75.8 pre-operatively to 83.9 post-operatively; p = 0.17). Subgroup analyses highlighted higher QoL and satisfaction following breast augmentation for purely esthetic purposes and alloplastic mammaplasty. Although patient-reported physical and sexual well-being increased in the long term, psychosocial well-being was the highest in the short term. CONCLUSION: Patient satisfaction with breast, psychosocial, and sexual well-being increased significantly after breast augmentation. In contrast, patient-reported physical well-being yielded ambivalent results, varying by mammaplasty technique and post-operative follow-up time. Plastic surgeons should be sensitized about our findings to refine eligibility criteria and gain a deeper understanding of the patients' perceived surgical experience. PROSPERO TRIAL REGISTRATION NO: CRD42023409605.

Characterization of Immune Cell Infiltration and Collagen Type III Disorganization in Human Secondary Lymphedema: A Case-control Study.

Background: Secondary lymphedema (SL) affects 120 million people globally, posing a lifelong burden for up to 37% of cancer survivors. Chronic inflammation and progressive fibrosis are key drivers of SL, yet detailed characterization of immune cell subpopulations across lymphedema stages is lacking. This study aimed to investigate the immunologic profile of lymphedematous skin and its association with extracellular matrix changes, which could serve as clinical biomarkers or therapeutic targets. Methods: This case-control study analyzed the skin from 36 patients with and without SL, using immunofluorescence to quantify T cells, B cells, macrophages, and their subpopulations. Collagen quantity and composition were examined using picrosirius red staining, and mast cell infiltration was assessed with toluidine blue staining. Early and late SL stages were compared to identify histomorphological and immunologic correlates of stage progression. Results: We found a predominance of CD4+ T cells and mast cells in SL skin (1.4/mm² versus 1.0/mm², P < 0.01; 1.2/mm² versus 0.2/mm², P < 0.0001) and a higher ratio of collagen III to collagen I fibers (51.6% versus 75.0%, P < 0.001). M2 macrophages were more abundant in late-stage than in early-stage lymphedema (1.7/mm² versus 1.0/mm², P = 0.02). Conclusions: This study demonstrated a shift toward CD4+ T cell and mast cell infiltration in SL skin, correlating with extracellular matrix disorganization and an altered collagen III/I ratio. These findings enhance our understanding of the cellular and morphological changes in SL, potentially guiding future diagnostic and therapeutic strategies.

Inferior long-term Results of a Prospective Randomized Controlled Trial initially demonstrating enhanced Sensory Nerve Recovery using a Chitosan Nerve Tube.

INTRODUCTION: Traumatic peripheral nerve injuries can result in significant functional impairments and long-term sequelae. This study evaluated the long-term outcomes of a chitosan tube implantation protecting the epineural coaptation after peripheral nerve injuries using two different tube versions (V 1.0 and V 2.0 with different wall thickness and resorption characteristics) compared to a control group. The study focused on pain levels, sensory function, and overall functional outcomes. METHODS: Patients who received tube implantation around direct coaptation sites of digital nerves were prospectively randomized and compared to control patients without additional tube protection. Pain levels, sensory function, grip force, and functional scores were assessed at different time points, ranging from three months to five years after the procedure. Furthermore, biodegradation of the tubes was measured via high-resolution MR-neurography (MRN) and categorized. RESULTS: Long-term evaluation revealed that patients with V 1.0 had higher pain levels compared to the control group after five years. They also reported more symptoms of numbness and hypersensitivity. V 2.0 patients exhibited higher pain levels at three months, which did not persist at six months. However, they showed compromised sensory function, with higher values of two-point discrimination compared to V 1.0 and the control group. No differences were found in grip force or functional scores between the groups. MRI displayed remnants of implants even in long-term follow-up. DISCUSSION: The findings suggest potential limitations due to pain increase and impaired sensory function associated with tube implantation in the long term. However, in the short term, the material seemed to have a protective effect (as published previously). The resorption process was not completed at the end of the observation period of five years. This might explain the prolonged scarring and inferior long-term results. Future research should focus on improving tube materials and design to minimize adverse effects and enhance functional outcomes in patients with peripheral nerve injuries.

The Application of a Synthetic Biodegradable Temporizing Matrix in Extensive Burn Injury: A Unicenter Experience of 175 Cases.

Objectives: Addressing extensive and deep burn wounds poses considerable challenges for both patients and surgeons. The NovoSorb® Biodegradable Temporizing Matrix (BTM) emerged as a novel dermal substitute and has been subjected to evaluation in large burn wound cases, with a specific focus on identifying risk factors associated with suboptimal take rates. Methods: All patients with burn wounds greater than 10% body surface that underwent BTM treatment between March 2020 and November 2023 were eligible for inclusion. Univariate analyses and linear regression models were employed to discern risk factors and predictors influencing the take rates of both the BTM and split-thickness skin grafts (STSGs). Results: A total of 175 patients (mean age 56.2 ± 19.8 years, 70.3% male) were evaluated. The mean take rates of the BTM and STSGs were 82.0 ± 24.7% and 87.3 ± 19.0%, respectively. There were significant negative correlations between BTM take and the number of surgeries before BTM application (r = -0.19, p = 0.01), %TBSA and STSG take (r = -0.36, p = <0.001) and significant positive correlations between BTM and STSG take (r = 0.41, p ≤ 0.001) in addition to NPWT and STSG take (r = 0.21, p = 0.01). Multivariate regression analyses showed that a larger number of surgeries prior to BTM application (OR -3.41, 95% CI -6.82, -0.03, p = 0.04) was associated with poorer BTM take. Allograft treatment before BTM application (OR -14.7, 95% CI -23.0, -6.43,p = 0.01) and failed treatment with STSG before BTM application (OR -20.8, 95% CI -36.3, -5.23, p ≤ 0.01) were associated with poorer STSG take, whereas higher BTM take rates were associated with overall higher STSG take (OR -0.15, 95% 0.05, 0.26, p = 0.01). The Meek technique was used in 24 patients and showed similar take rates (BTM: 76.3 ± 28.0%, p = 0.22; STSG: 80.7 ± 21.1, p = 0.07). Conclusions: This study summarizes our findings on the application of a BTM in the context of large burn wounds. The results demonstrate that successful treatment can be achieved even in patients with extensive burns, resulting in satisfying take rates for both the BTM and STSG. The data underscore the importance of promptly applying a BTM to debrided wounds and indicate good results when using Meek.

How Framing Bias Impacts Preferences for Innovation in Bone Tissue Engineering.

It is currently unknown if surgeons and biomaterial scientists &or tissue engineers (BS&orTE) process and evaluate information in similar or different (un)biased ways. For the gold standard of surgery to move "from bench to bedside," there must naturally be synergies between these key stakeholders' perspectives. Because only a small number of biomaterials and tissue engineering innovations have been translated into the clinic today, we hypothesized that this lack of translation is rooted in the psychology of surgeons and BS&orTE. Presently, both clinicians and researchers doubt the compatibility of surgery and research in their daily routines. This has led to the use of a metaphorical expression "squaring of the circle," which implies an unsolvable challenge. As bone tissue engineering belongs to the top five research areas in tissue engineering, we choose the field of bone defect treatment options for our bias study. Our study uses an online survey instrument for data capture such as incorporating a behavioral economics cognitive framing experiment methodology. Our study sample consisted of surgeons (n = 208) and BS&orTE (n = 59). And we used a convenience sampling method, with participants (conference attendants) being approached both in person and through email between October 22, 2022, and March 13, 2023. We find no distinct positive-negative cognitive framing differences by occupation. That is, any framing bias present in this surgical decision-making setting does not appear to differ significantly between surgeon and BS&orTE specialization. When we explored within-group differences by frames, we see statistically significant (p < 0.05) results for surgeons in the positive frame ranking autologous bone graft transplantation lower than surgeons in the negative frame. Furthermore, surgeons in the positive frame rank Ilizarov bone transport method higher than surgeons in the negative frame (p < 0.05).

Elevated Shear Stress Modulates Heterogenous Cellular Subpopulations to Induce Vascular Remodeling.

Rationale: Elevated shear stress (ESS) induces vascular remodeling in veins exposed to arterial blood flow, which can lead to arteriovenous (AV) fistula failure. The molecular mechanisms driving remodeling have not been comprehensively examined with a single-cell resolution before. Objective: Using an in vivo animal mode, single-cell RNA sequencing, and histopathology, we precisely manipulate blood flow to comprehensively characterize all cell subpopulations important during vascular remodeling. Methods: AV loops were created in saphenous vessels of rats using a contralateral saphenous vein interposition graft to promote ESS. Saphenous veins with no elevated shear stress (NSS) were anastomosed as controls. Findings: ESS promoted transcriptional homogeneity, and NSS promoted considerable heterogeneity. Specifically, ESS endothelial cells (ECs) showed a more homogeneous transcriptional response promoting angiogenesis and upregulating endothelial-to-mesenchymal transition inhibiting genes (Klf2). NSS ECs upregulated antiproliferation genes such as Cav1, Cst3, and Btg1. In macrophages, ESS promoted a large homogeneous subpopulation, creating a mechanically activated, proinflammatory and thus proangiogenic myeloid phenotype, whereas NSS myeloid cells expressed the anti-inflammatory and antiangiogenetic marker Mrc1. Conclusion: ESS activates unified gene expression profiles to induce adaption of the vessel wall to hemodynamic alterations. Targeted depletion of the identified cellular subpopulations may lead to novel therapies to prevent excessive venous remodeling, intimal hyperplasia, and AV fistula failure.

[Modern concepts of interdisciplinary extremity reconstruction in open fractures]. / Moderne Konzepte der interdisziplinären Extremitätenrekonstruktion bei offenen Frakturen.

The orthoplastic approach involves the collaboration of orthopedic/trauma surgeons, vascular surgeons and reconstructive microsurgeons. In cases of complex limb fractures, the aims are to optimize blood flow, restore bone stability, reconstruct soft tissue defects, and enhance function and sensitivity. The early administration of antibiotics and a timely, high-quality debridement after initial interdisciplinary assessment are carried out. This is followed by fracture stabilization and temporary wound coverage in order to plan the definitive interdisciplinary procedure. This includes definitive osteosynthesis and soft tissue reconstruction, using local tissue transfer if feasible, or free tissue transfer in cases of extensive trauma zones. The orthoplastic approach allows for faster definitive stabilization, fewer operations, shorter hospital stays, lower complication and revision rates, higher cost-effectiveness and improved long-term function.

Free Flap Reconstruction of Sternal Defects after Cardiac Surgery: An Algorithmic Approach for Dealing with Sparse Recipient Vessels.

Background: Sparsity of recipient vessels poses a challenge for microsurgical free flap reconstruction of sternal defects following deep sternal wound infection after cardiac surgery. Methods: From January 2013, a standardized algorithm for dealing with sparse recipient vessels was strictly followed. In this retrospective study including 75 patients, we compared operative details, surgical complications, and reconstructive outcomes of patients treated according to this algorithm (group A: January 2013-May 2021; n = 46) with a historical control group (group B: January 2000-December 2012, n = 29). Results: The left internal mammary artery had been harvested for arterial bypass grafting in 40 of 46 cases (87%) in group A and in all cases in group B. The right internal mammary artery (RIMA) and right internal mammary vein (RIMV) were the first choice as recipient vessels. In case of unsuitability of the RIMV, a right cephalic vein (CV) turndown was used for venous outflow. If both RIMA and RIMV proved insufficient, a single-stage arterio-venous loop (AVL) between the CV and subclavian artery (CV-SA AVL), CV and thoracoacromial artery (CV-TA AVL), or subclavian artery and subclavian vein (SA-SV AVL) was established. The algorithmic approach significantly reduced partial flap necrosis [group A: n = 3 (7%) versus group b: n = 7 (24%); P = 0.04], and overall operation time [group A: 360 ±â€…88 min versus group B: 415 ±â€…80 min; P = 0.01]. Conclusions: Standardized approaches improve clinical outcomes in microsurgical free flap sternal reconstruction after cardiac surgery.

Fibrin Glue Coating Limits Scar Tissue Formation around Peripheral Nerves.

Scar tissue formation presents a significant barrier to peripheral nerve recovery in clinical practice. While different experimental methods have been described, there is no clinically available gold standard for its prevention. This study aims to determine the potential of fibrin glue (FG) to limit scarring around peripheral nerves. Thirty rats were divided into three groups: glutaraldehyde-induced sciatic nerve injury treated with FG (GA + FG), sciatic nerve injury with no treatment (GA), and no sciatic nerve injury (Sham). Neural regeneration was assessed with weekly measurements of the visual static sciatic index as a parameter for sciatic nerve function across a 12-week period. After 12 weeks, qualitative and quantitative histological analysis of scar tissue formation was performed. Furthermore, histomorphometric analysis and wet muscle weight analysis were performed after the postoperative observation period. The GA + FG group showed a faster functional recovery (6 versus 9 weeks) compared to the GA group. The FG-treated group showed significantly lower perineural scar tissue formation and significantly higher fiber density, myelin thickness, axon thickness, and myelinated fiber thickness than the GA group. A significantly higher wet muscle weight ratio of the tibialis anterior muscle was found in the GA + FG group compared to the GA group. Our results suggest that applying FG to injured nerves is a promising scar tissue prevention strategy associated with improved regeneration both at the microscopic and at the functional level. Our results can serve as a platform for innovation in the field of perineural regeneration with immense clinical potential.

Administration and effects of beta blockers and oxandrolone in severely burned adults: a post hoc analysis of the RE-ENERGIZE trial.

Background: Prospective randomized trials in severely burned children have shown the positive effects of oxandrolone (OX), beta blockers (BB) and a combination of the two (BBOX) on hypermetabolism, catabolism and hyperinflammation short- and long-term post-burn. Although data on severely burned adults are lacking in comparison, BB, OX and BBOX appear to be commonly employed in this patient population. In this study, we perform a secondary analysis of an international prospective randomized trial dataset to provide descriptive evidence regarding the current utilization patterns and potential treatment effects of OX, BB and BBOX. Methods: The RE-ENERGIZE (RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury, NCT00985205) trial included 1200 adult patients with severe burns. We stratified patients according to their receipt of OX, BB, BBOX or none of these drugs (None) during acute hospitalization. Descriptive statistics describe the details of drug therapy and unadjusted analyses identify predisposing factors for drug use per group. Association between OX, BB and BBOX and clinical outcomes such as time to discharge alive and 6-month mortality were modeled using adjusted multivariable Cox regressions. Results: More than half of all patients in the trial received either OX (n = 138), BB (n = 293) or BBOX (n = 282), as opposed to None (n = 487, 40.6%). Per study site and geographical region, use of OX, BB and BBOX was highly variable. Predisposing factors for the use of OX, BB and BBOX included larger total body surface area (TBSA) burned, higher acute physiology and chronic health evaluation (APACHE) II scores on admission and younger patient age. After adjustment for multiple covariates, the use of OX was associated with a longer time to discharge alive [hazard ratio (HR) 0.62, confidence interval (CI) (0.47-0.82) per 100% increase, p = 0.001]. A higher proportion of days on BB was associated with lower in-hospital-mortality (HR: 0.5, CI 0.28-0.87, p = 0.015) and 6-month mortality (HR: 0.44, CI 0.24-0.82, p = 0.01). Conclusions: The use of OX, BB and BBOX is common within the adult burn patient population, with its use varying considerably across sites worldwide. Our findings found mixed associations between outcomes and the use of BB and OX in adult burn patients, with lower acute and 6-month-mortality with BB and longer times to discharge with OX. Further research into these pharmacological modulators of the pathophysiological response to severe burn injury is indicated.

In Vivo Engineering and Transplantation of Axially Vascularized and Epithelialized Flaps in Rats.

The arteriovenous loop (AVL) model allows the in vivo engineering of axially vascularized flaps, the so-called AVL flaps. Although AVL flaps can be transplanted microsurgically to cover tissue defects, they lack an epithelial layer on the surface. Therefore, the objective of this study was to engineer axially vascularized AVL flaps with an accompanying epithelial layer for local defect reconstruction. In this study, AVLs were established in 20 male Lewis rats. Minimally invasive injection of keratinocytes onto the surface of the AVL flaps was performed on postoperative day (POD) 21. AVL flaps were explanted from 12 rats on POD 24 or POD 30, then the epithelium formed by the keratinocytes on the surface of the flaps was evaluated using immunofluorescence staining. In six other rats, the AVL flap was locally transposed to cover a critical defect in the rats' leg on POD 30 and explanted for analysis on POD 40. In two control rats, sodium chloride was applied instead of keratinocytes. These control flaps were also transplanted on POD 30 and explanted on POD 40. Our results revealed that 3 days after keratinocyte application, a loose single-layered epithelium was observed histologically on the AVL flaps surface, whereas after 9 days, a multilayered and structured epithelium had grown. The epithelium on the transplanted AVL flaps showed its physiological differentiation when being exposed to an air-liquid interface. Histologically, a layered epithelium identical to the rats' regular skin was formed. In the sodium chloride control group, no epithelium had been grown. This study clearly demonstrates that axially vascularized AVL flaps can be processed in the subcutaneous chamber by minimally invasive injection of keratinocytes. Thus, AVL flaps with an intact epithelial layer were engineered and could be successfully transplanted for local defect coverage in a small animal model.

Hypoxia as a stimulus for tissue formation: The concept of organogenesis in microsurgically vascularized tissue engineering constructs.

Axial vascularization of tissue constructs is essential to maintain an adequate blood supply for a stable regeneration of a clinically relevant tissue size. The versatility of the arterio-venous loop (AVL) has been previously shown in various small and large animal models as well as in clinical reports for bone regeneration. We have previously demonstrated the capability of the AVL to induce axial vascularization and to support the nourishment of tissue constructs in small animal models after applying high doses of ionizing radiation comparable to those applied for adjuvant radiotherapy after head and neck cancer. We hypothesize that this robust ability to induce regeneration after irradiation could be related to a state of hypoxia inside the constructs that triggers the HIF1 (hypoxia induced factor 1) - SDF1 (stromal derived factor 1) axis leading to chemotaxis of progenitor cells and induction of tissue regeneration and vascularization. We analyzed the expression of HIF1 and SDF1 via immunofluorescence in axially vascularized bone tissue engineering constructs in Lewis rats 2 and 5 weeks after local irradiation with 9Gy or 15Gy. We also analyzed the expression of various genes for osteogenic differentiation (collagen 1, RUNX, alkaline phosphatase and osteonectin) via real time PCR analysis. The expression of HIF1 and SDF1 was enhanced two weeks after irradiation with 15Gy in comparison to non-irradiated constructs. The expression of osteogenic markers was enhanced at the 5-weeks time point with significant results regarding collagen, alkaline phosphatase and osteonectin. These results indicate that the hypoxia within the AVL constructs together with an enhanced SDF1 expression probably play a role in promoting tissue differentiation. The process of tissue generation triggered by hypoxia in the vicinity of a definite vascular axis with enhanced tissue differentiation over time resembles hereby the well-known concept of organogenesis in fetal life.