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.

[Robotic-Assisted DIEP Flap Harvest for Autologous Breast Reconstruction: Case Report, Technical Aspects and Identification of Suitable Patients]. / Die robotisch-assistierte Hebung der DIEP-Lappenplastik zur Brustrekonstruktion: Fallbericht, technische Aspekte und Identifikation geeigneter Patientinnen.

BACKGROUND: Robotic-assisted harvest of the deep inferior epigastric perforator (DIEP) flap is an innovative modification of the traditional open preparation for autologous breast reconstruction. It is assumed that donor-site morbidity (herniae, bulging) is reduced by minimising the fascial incision length in robotic-assisted DIEP flap harvest. MATERIAL & METHODS: This is the first report of a robotic-assisted DIEP harvest in Germany, which was performed in April 2023 at the University Hospital of Freiburg in an interdisciplinary approach of the Departments of Plastic Surgery, Urology and Gynaecology. To determine the value of this novel technique, we assessed the demand by retrospectively performing an analysis of potential patients and conducted a cost analysis based on the breast reconstructions with DIEP flap harvest performed between April 2021 and May 2023 at the Department of Plastic Surgery at Freiburg University Hospital. To this end, we carried out a retrospective analysis of preoperative CT angiographies to determine the proportion of patients suitable for a robotic-assisted procedure in a post-hoc analysis. Furthermore, we describe the basic robotic-assisted techniques and discuss the TEP and TAPP laparoscopic approaches. RESULTS: In line with the previously published literature, a short intramuscular course (≤25 mm) and a perforator diameter of≥1.5 mm and≥2.7 mm (subgroup) were defined as a crucial condition for the robotic-assisted procedure. We analysed 65 DIEP flaps harvested in 51 patients, of which 26 DIEP flaps in 22 patients met both criteria, i. e.≤25 mm intramuscular course and≥1.5 mm diameter of the perforator, while 10 DIEP flaps in 10 patients additionally met the criteria of the subgroup (≥2.7 mm diameter). Based on the intramuscular course of the perforators in the CT angiographies of those 26 DIEP flaps, a potential reduction of the fascial incision of 96.8±25.21 mm (mean±standard deviation) compared with the conventional surgical approach was calculated. The additional material costs in our case were EUR 986.01. However, ischaemia time was 33,5 minutes longer than the median of the comparative cohort. CONCLUSION: The robotic-assisted procedure has already proven to be a feasible alternative in a suitable patient population. However, further studies are needed to confirm that robotic-assisted DIEP flap harvest actually reduces harvest site morbidity and thereby justifies the additional costs and complexity.

Non-invasive monitoring of neoadjuvant radiation therapy response in soft tissue sarcomas by multiparametric MRI and quantification of circulating tumor DNA-A study protocol.

BACKGROUND: Wide resection remains the cornerstone of localized soft-tissue sarcomas (STS) treatment. Neoadjuvant radiation therapy (NRT) may decrease the risk of local recurrences; however, its effectiveness for different histological STS subtypes has not been systematically investigated. The proposed prospective study evaluates the NRT response in STS using liquid biopsies and the correlation of multiparametric magnetic resonance imaging (mpMRI) with histopathology and immunohistochemistry. METHODS: Patients with localized high-grade STS, who qualify for NRT, are included in this study. LIQUID BIOPSIES: Quantification of circulating tumor DNA (ctDNA) in patient blood samples is performed by targeted next-generation sequencing. Soft-tissue sarcoma subtype-specific panel sequencing in combination with patient-specific exome sequencing allows the detection of individual structural variants and point mutations. Circulating free DNA is isolated from peritherapeutically collected patient plasma samples and ctDNA quantified therein. Identification of breakpoints is carried out using FACTERA. Bioinformatic analysis is performed using samtools, picard, fgbio, and the MIRACUM Pipeline. MPMRI: Combination of conventional MRI sequences with diffusion-weighted imaging, intravoxel-incoherent motion, and dynamic contrast enhancement. Multiparametric MRI is performed before, during, and after NRT. We aim to correlate mpMRI data with the resected specimen's macroscopical, histological, and immunohistochemical findings. RESULTS: Preliminary data support the notion that quantification of ctDNA in combination with tumor mass characterization through co-registration of mpMRI and histopathology can predict NRT response of STS. CLINICAL RELEVANCE: The methods presented in this prospective study are necessary to assess therapy response in heterogeneous tumors and lay the foundation of future patient- and tumor-specific therapy concepts. These methods can be applied to various tumor entities. Thus, the participation and support of a wider group of oncologic surgeons are needed to validate these findings on a larger patient cohort.

Secondary dynamic midface reanimation with gracilis free muscle transfer after failed reconstruction attempt: A 15-year experience.

BACKGROUND: The quantitative outcome of secondary reanimation after a failed primary reconstruction attempt for facial paralysis is rarely reported in the literature. This study aimed to investigate the feasibility of secondary reanimation with gracilis free muscle transfer (GFMT) and whether this outcome is influenced by the primary reconstruction. METHODS: Twelve patients with previously failed static procedures (static group, n = 6), temporal muscle transfer (temporal transfer group, n = 2), and GFMT (GFMT group, n = 4) were all secondarily reanimated with GFMT. The clinical outcome was graded with the eFACE metric. The objective oral commissure excursion was measured with Emotrics, and the artificial intelligence software FaceReader evaluated the intensity score (IS) of emotional expression. RESULTS: The mean follow-up was 40 ± 27 months. The eFACE metric showed a statistically significant (p < 0.05) postoperative improvement in the dynamic and smile scores across all groups. In the GFMT group, oral commissure with smile (75.75 ± 20.43 points), oral commissure excursion while smiling with teeth showing (32.7 ± 4.35 mm), and the intensity of happiness emotion while smiling without teeth showing (IS of 0.37 ± 0.23) were significantly lower as compared with the static group postoperatively (98.83 ± 2.86 points, p = 0.038; 41.7 ± 4.35 mm, p = 0.025; IS 0.83 ± 0.16, p = 0.01). CONCLUSIONS: Our data suggest that secondary dynamic reconstruction with GFMT is feasible should the primary reconstruction fail. The secondary GFMT appears to improve the outcome of primary GFMT; however, the oral commissure excursion while smiling might be lower than that in patients who had static procedures as primary reconstruction.

Special Issue: Evidence-Based Diagnosis and Management of Facial Nerve Disorders.

Although there has been a rapid increase in the number of new publications and studies in relation to the diagnostics, impacts and rehabilitation methods of facial nerve disorders, a general structure in evidence-based medicine is still difficult to establish [...].

Age-related outcomes of facial reanimation surgery using gracilis free functional muscle transfer innervated by the masseteric nerve: A retrospective cohort study.

BACKGROUND: The free functional muscle gracilis transfer is an established approach in facial reanimation surgery; however, the significance of its neurotization and the patient's age is still inconclusive. Several donor nerves are available for facial reanimation using the free functional gracilis muscle transfer. OBJECTIVE: This retrospective cohort study investigates whether the masseteric nerve is an equally reliable donor nerve in both older and younger patients. METHODS: We included 46 patients (13-71 years, male and female) who underwent nerve-to-masseter (NTM)-driven free functional muscle transfer (FFMT) between January 2008 and December 2019. Patients were distributed into three cohorts according to their age at surgery. We assessed the facial symmetry before and after surgery using the pupillo-modiolar angle. Commissure height and excursion deviation were measured with the Emotrics software. Patient-reported outcome measurements were taken using the Facial Clinimetric Examination (FaCE) scale. RESULTS: All patients had successful flap innervation, except for one patient in the middle-aged cohort (31-51 years). The postoperative facial symmetry at rest, smiling, and laughing was analyzed with the pupillo-modiolar angle and the Emotrics software and showed similar results between all cohorts. The FaCE scale showed similar scores for the middle-aged (31-51 years) cohort and the senior cohort (52-71 years). The social function score in the senior cohort was higher than in the middle-aged cohort, without statistical significance. One patient in the middle-aged (31-51 years) cohort and the senior cohort (52-71 years), respectively, underwent emergency revision due to impaired flap perfusion and could be salvaged. CONCLUSIONS: NTM-driven FFMT for facial reanimation is a safe and reliable procedure across all age groups of patients.

Correlation between facial vascularized composite allotransplantation rejection and laboratory markers: Insights from a retrospective study of eight patients.

BACKGROUND: The field of facial vascularized composite allotransplantation (fVCA) is still new and a limited number of patients have undergone the procedure. This has led to a lack of understanding about the impact of fVCA rejection on standard laboratory markers (e.g., CBC, BMP, CRP) for the acute management of these patients. It is not clear if rejection elicits a systemic inflammatory response that influences common inflammatory markers such as WBC and CRP. A comprehensive understanding of changes in these markers could help in the management of fVCA patients in the acute setting. METHODS: The medical records of 8 fVCA patients with a total of 9 transplants were reviewed retrospectively, and data on standard laboratory values (CBC, BMP, LFTs, CRP) and vital signs were extracted. To examine the relationship between laboratory values and rejection status, linear mixed models were used to analyze the data, taking into account their longitudinal nature (repeated measures). RESULTS: A statistically significant relationship was found between the Banff grade of rejection and the relative number of basophils in the patient's blood during rejection (p = 0.005). In addition, in patients with clinical signs of rejection (e.g., facial erythema, edema) and skin biopsy showing Banff ≥ II, CRP was found to be significantly elevated (p = 0.03). The WBC count remained stable during rejection, and the relative number of neutrophils was lower at the time of rejection, indicating possible consumption at the site of rejection. CONCLUSION: During fVCA rejection, most standard laboratory parameters and vital signs appear to be stable. However, the levels of CRP and basophils were elevated during rejection, while the neutrophil count was lower. Leukocytosis can likely be used as a marker of microbial infection in fVCA patients, as WBC does not seem to increase at the time of allograft rejection.

Functional Outcome of Dual Reinnervation with Cross-Facial Nerve Graft and Masseteric Nerve Transfer for Facial Paralysis.

BACKGROUND: The combination of cross-facial nerve graft (CFNG) and masseteric nerve transfer (MNT) for reinnervation of facial paralysis may provide advantages of both neural sources. However, quantitative functional outcome reports with a larger number of patients are lacking in the literature. Here we describe our 8-year experience with this surgical technique. METHODS: Twenty patients that presented with a complete facial paralysis (duration <12 months) received dual reinnervation with CFNG and MNT. The functional outcome of the procedure was evaluated with the physician-graded outcome metric eFACE. The objective artificial intelligence-driven software Emotrics and FaceReader were used for oral commissure measurements and emotional expression assessment, respectively. RESULTS: The mean follow-up was 31.75±23.32 months. In the eFACE score, the nasolabial fold depth and oral commissure at rest improved significantly (p<0.05) towards a more balanced state after the surgery. Postoperatively, there was a significant decrease in oral commissure asymmetry while smiling (19.22±6.1mm to 12.19±7.52mm). For the emotionality expression, the median intensity score of happiness, as measured by the FaceReader software, increased significantly while smiling (0.28, IQR 0.13-0.64). In 5 (25%) patients, a secondary static midface suspension with fascia lata strip had to be performed due to an unsatisfactory resting symmetry. Older patients and patients with greater preoperative resting asymmetry were more likely to receive static midface suspension. CONCLUSIONS: Our results suggest that the combination of MNT and CFNG for reinnervation of facial paralysis provides good voluntary motion and may lessen the use of static midface suspension in the majority of patients.

Dermatofibrosarcoma protuberans of the scalp: Surgical management in a multicentric series of 11 cases and systematic review of the literature.

BACKGROUND: Dermatofibrosarcoma protuberans is a rare, slow-growing soft-tissue malignancy originating in the dermis that is characterized by an infiltrating growth pattern with a marked tendency of local recurrence. Complete surgical resection with pathological margin clearance must be achieved to reduce the risk of tumor recurrence. Resulting defects often require extensive reconstructive procedures. Dermatofibrosarcoma protuberans of the scalp poses particular challenges owing to the proximity to the face and brain. This study aims to evaluate treatment options and proposes an algorithm for management of scalp dermatofibrosarcoma protuberans based on a multicentric case series and systematic review of the literature. METHODS: A retrospective multicentric chart analysis of 11 patients with scalp dermatofibrosarcoma protuberans who presented within the last 20 years was performed regarding demographic data, pathological tumor characteristics, and surgical management (resection and reconstruction). Additionally, a further 42 patients (44 cases) were identified through a systematic Preferred Reporting Systems for Systematic Reviews and Meta-Analysis-based review of the literature searching the Medline and Embase databases. RESULTS: In total, 30 cases were classified as primary and 20 cases as recurring scalp dermatofibrosarcoma protuberans (data from 5 cases were missing). The median tumor size was 24 cm2 (interquartile range 7.8-64), and the median defect size was 55.8 cm2 (interquartile range 48-112). Recurring scalp dermatofibrosarcoma protuberans was more often associated with invasion of deeper layers and required more extensive tumor resection to achieve negative margins. Within the subgroup that was managed with peripheral and deep en face margin assessment, no recurrence was observed. Most patients required local (41. 8%) or free flap (27.8%) reconstruction after dermatofibrosarcoma protuberans resection. CONCLUSION: Whenever possible, peripheral and deep en face margin assessment-based techniques should be preferred for resection of scalp dermatofibrosarcoma protuberans because they provide superior oncological safety while preserving uninvolved tissue. Patients with locally advanced and recurring scalp dermatofibrosarcoma protuberans often require multidisciplinary treatment including neurosurgery, radiotherapy, and microvascular reconstructive surgery and should be referred to a specialized center.

Multiparametric magnetic resonance imaging for radiation therapy response monitoring in soft tissue sarcomas: a histology and MRI co-registration algorithm.

Rationale: To establish a spatially exact co-registration procedure between in vivo multiparametric magnetic resonance imaging (mpMRI) and (immuno)histopathology of soft tissue sarcomas (STS) to identify imaging parameters that reflect radiation therapy response of STS. Methods: The mpMRI-Protocol included diffusion-weighted (DWI), intravoxel-incoherent motion (IVIM), and dynamic contrast-enhancing (DCE) imaging. The resection specimen was embedded in 6.5% agarose after initial fixation in formalin. To ensure identical alignment of histopathological sectioning and in vivo imaging, an ex vivo MRI scan of the specimen was rigidly co-registered with the in vivo mpMRI. The deviating angulation of the specimen to the in vivo location of the tumor was determined. The agarose block was trimmed accordingly. A second ex vivo MRI in a dedicated localizer with a 4 mm grid was performed, which was matched to a custom-built sectioning machine. Microtomy sections were stained with hematoxylin and eosin. Immunohistochemical staining was performed with anti-ALDH1A1 antibodies as a radioresistance and anti-MIB1 antibodies as a proliferation marker. Fusion of the digitized microtomy sections with the in vivo mpMRI was accomplished through nonrigid co-registration to the in vivo mpMRI. Co-registration accuracy was qualitatively assessed by visual assessment and quantitatively evaluated by computing target registration errors (TRE). Results: The study sample comprised nine tumor sections from three STS patients. Visual assessment after nonrigid co-registration showed a strong morphological correlation of the histopathological specimens with ex vivo MRI and in vivo mpMRI after neoadjuvant radiation therapy. Quantitative assessment of the co-registration procedure using TRE analysis of different pairs of pathology and MRI sections revealed highly accurate structural alignment, with a total median TRE of 2.25 mm (histology - ex vivo MRI), 2.22 mm (histology - in vivo mpMRI), and 2.02 mm (ex vivo MRI - in vivo mpMRI). There was no significant difference between TREs of the different pairs of sections or caudal, middle, and cranial tumor parts, respectively. Conclusion: Our initial results show a promising approach to obtaining accurate co-registration between histopathology and in vivo MRI for STS. In a larger cohort of patients, the method established here will enable the prospective identification and validation of in vivo imaging biomarkers for radiation therapy response prediction and monitoring in STS patients via precise molecular and cellular correlation.

Newly identified axon types of the facial nerve unveil supplemental neural pathways in the innervation of the face.

INTRODUCTION: Neuromuscular control of the facial expressions is provided exclusively via the facial nerve. Facial muscles are amongst the most finely tuned effectors in the human motor system, which coordinate facial expressions. In lower vertebrates, the extracranial facial nerve is a mixed nerve, while in mammals it is believed to be a pure motor nerve. However, this established notion does not agree with several clinical signs in health and disease. OBJECTIVES: To elucidate the facial nerve contribution to the facial muscles by investigating axonal composition of the human facial nerve. To reveal new innervation pathways of other axon types of the motor facial nerve. METHODS: Different axon types were distinguished using specific molecular markers (NF, ChAT, CGRP and TH). To elucidate the functional role of axon types of the facial nerve, we used selective elimination of other neuronal support from the trigeminal nerve. We used retrograde neuronal tracing, three-dimensional imaging of the facial muscles, and high-fidelity neurophysiological tests in animal model. RESULTS: The human facial nerve revealed a mixed population of only 85% motor axons. Rodent samples revealed a fiber composition of motor, afferents and, surprisingly, sympathetic axons. We confirmed the axon types by tracing the originating neurons in the CNS. The sympathetic fibers of the facial nerve terminated in facial muscles suggesting autonomic innervation. The afferent fibers originated in the facial skin, confirming the afferent signal conduction via the facial nerve. CONCLUSION: These findings reveal new innervation pathways via the facial nerve, support the sympathetic etiology of hemifacial spasm and elucidate clinical phenomena in facial nerve regeneration.

Application of fibrin glue for hematoma prophylaxis in selective aponeurectomy in Dupuytren's disease.

INTRODUCTION: Fibrin glue (FG) can be applied in several surgical procedures at wound closure to reduce postoperative complications such as hematoma formation and wound impairment. The purpose of this study is to assess these preventive surgical benefits in Dupuytren's disease of the hand. PATIENTS AND METHODS: We performed a monocentric retrospective cohort study. All patients who underwent selective aponeurectomy for Dupuytren's disease between 2010 and 2020 were included. Patients were divided into two groups: either receiving or not receiving FG. The primary outcome variables were postoperative bleeding, wound healing impairment, and further pooled postoperative complications. RESULTS: One hundred and thirty-three patients were included in the analysis of which 108 patients were treated with FG, while 24 did not. There was no statistically significant difference in outcomes regarding postoperative bleeding, infections, or revision surgery. However, in the group receiving FG, there was a tendency toward higher wound healing impairment (13%, p = 0.07). The FG group showed a significantly higher pooled complication rate (18.5%, p < 0.02). Complication in general increased with higher Tubiana classification and number of resected cords. Smoking tripled the risk of impaired wound, while cardiovascular comorbidities increased postoperative bleeding by the factor of 11. CONCLUSION: FG did not show a preventive outcome regarding bleeding. The FG group had a tendency for a higher wound healing incidence. Smoking and arterial hypertension correlated with a higher postoperative complication rate. The overall incidence of complications was higher in the FG group. The quality of the surgical intervention as well as accurate hemostasis cannot be corrected by the application of FG.

A novel phosphocholine-mimetic inhibits a pro-inflammatory conformational change in C-reactive protein.

C-reactive protein (CRP) is an early-stage acute phase protein and highly upregulated in response to inflammatory reactions. We recently identified a novel mechanism that leads to a conformational change from the native, functionally relatively inert, pentameric CRP (pCRP) structure to a pentameric CRP intermediate (pCRP*) and ultimately to the monomeric CRP (mCRP) form, both exhibiting highly pro-inflammatory effects. This transition in the inflammatory profile of CRP is mediated by binding of pCRP to activated/damaged cell membranes via exposed phosphocholine lipid head groups. We designed a tool compound as a low molecular weight CRP inhibitor using the structure of phosphocholine as a template. X-ray crystallography revealed specific binding to the phosphocholine binding pockets of pCRP. We provide in vitro and in vivo proof-of-concept data demonstrating that the low molecular weight tool compound inhibits CRP-driven exacerbation of local inflammatory responses, while potentially preserving pathogen-defense functions of CRP. The inhibition of the conformational change generating pro-inflammatory CRP isoforms via phosphocholine-mimicking compounds represents a promising, potentially broadly applicable anti-inflammatory therapy.

C-reactive protein, immunothrombosis and venous thromboembolism.

C-reactive protein (CRP) is a member of the highly conserved pentraxin superfamily of proteins and is often used in clinical practice as a marker of infection and inflammation. There is now increasing evidence that CRP is not only a marker of inflammation, but also that destabilized isoforms of CRP possess pro-inflammatory and pro-thrombotic properties. CRP circulates as a functionally inert pentameric form (pCRP), which relaxes its conformation to pCRP* after binding to phosphocholine-enriched membranes and then dissociates to monomeric CRP (mCRP). with the latter two being destabilized isoforms possessing highly pro-inflammatory features. pCRP* and mCRP have significant biological effects in regulating many of the aspects central to pathogenesis of atherothrombosis and venous thromboembolism (VTE), by directly activating platelets and triggering the classical complement pathway. Importantly, it is now well appreciated that VTE is a consequence of thromboinflammation. Accordingly, acute VTE is known to be associated with classical inflammatory responses and elevations of CRP, and indeed VTE risk is elevated in conditions associated with inflammation, such as inflammatory bowel disease, COVID-19 and sepsis. Although the clinical data regarding the utility of CRP as a biomarker in predicting VTE remains modest, and in some cases conflicting, the clinical utility of CRP appears to be improved in subsets of the population such as in predicting VTE recurrence, in cancer-associated thrombosis and in those with COVID-19. Therefore, given the known biological function of CRP in amplifying inflammation and tissue damage, this raises the prospect that CRP may play a role in promoting VTE formation in the context of concurrent inflammation. However, further investigation is required to unravel whether CRP plays a direct role in the pathogenesis of VTE, the utility of which will be in developing novel prophylactic or therapeutic strategies to target thromboinflammation.

Individualized Mini-Panel Sequencing of ctDNA Allows Tumor Monitoring in Complex Karyotype Sarcomas.

Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin with high mortality. After curative resection, about one third of patients suffer from distant metastases. Tumor follow-up only covers a portion of recurrences and is associated with high cost and radiation burden. For metastasized STS, only limited inferences can be drawn from imaging data regarding therapy response. To date there are no established and evidence-based diagnostic biomarkers for STS due to their rarity and diversity. In a proof-of-concept study, circulating tumor DNA (ctDNA) was quantified in (n = 25) plasma samples obtained from (n = 3) patients with complex karyotype STS collected over three years. Genotyping of tumor tissue was performed by exome sequencing. Patient-individual mini-panels for targeted next-generation sequencing were designed encompassing up to 30 mutated regions of interest. Circulating free DNA (cfDNA) was purified from plasma and ctDNA quantified therein. ctDNA values were correlated with clinical parameters. ctDNA concentrations correlated with the tumor burden. In case of full remission, no ctDNA was detectable. Patients with a recurrence at a later stage showed low levels of ctDNA during clinical remission, indicating minimal residual disease. In active disease (primary tumor or metastatic disease), ctDNA was highly elevated. We observed direct response to treatment, with a ctDNA decline after tumor resections, radiotherapy, and chemotherapy. Quantification of ctDNA allows for the early detection of recurrence or metastases and can be used to monitor treatment response in STS. Therapeutic decisions can be made earlier, such as the continuation of a targeted adjuvant therapy or the implementation of extended imaging to detect recurrences. In metastatic disease, therapy can be adjusted promptly in case of no response. These advantages may lead to a survival benefit for patients in the future.

An Analysis of the Implantable Doppler Probe for Postoperative Free-Flap Monitoring and Risk Factor Analysis for Revision Surgery in Facial Reanimation Surgery.

Background: Postoperative monitoring after free functional gracilis transfer for smile reconstruction in long-standing facial paralysis is challenging as clinical assessments are limited. Objective: In patients receiving free gracilis transfer for smile reconstruction, we compared the implantable Doppler probe with a handheld Doppler/intraoperative blood flow regarding the reliability in detecting perfusion compromised free flaps. Methods: In a retrospective cohort study we analyzed facial paralysis patients who, after free functional smile reconstruction, were postoperatively monitored using the implantable Doppler probe. Furthermore, we conducted a multiple logistic regression analysis on risk factors for vascular complications. Results: We included 119 patients who received 125 free functional gracilis transfers. The sensitivity of the implanted Doppler probe was 1.0 and the specificity 0.88. There were no false-negative results (negative predictive value = 1.0). The calculated positive predictive value was 0.41. We used a handheld Doppler device to verify signal changes. The combined positive predictive value of both tests was 0.91. Previous surgery in the surgical field was a risk factor for impaired blood flow. Conclusions: The implantable Doppler probe proved to be a reliable tool for postoperative monitoring of free functional gracilis transfer in facial reanimation surgery. Special care should be taken in preoperated patients.

Autologous free tissue transfer in paediatric patient with a univentricular heart.

We report on the case of a 30-month-old boy who developed severe deep cervical necrosis after bypass surgery for total cavopulmonary connection, followed by low-cardiac output and extracorporeal life support. As several bedside debridements failed to result in sufficient wound healing, a 2-stage necrectomy followed by autologous reconstruction with a free anterolateral thigh-flap was required. Due to impaired circulation, postoperative flap monitoring was extremely difficult. To ensure flap perfusion, mean arterial pressure had to be raised by catecholamines over 7 days.

Risk factors in distal interphalangeal joint arthrodesis in the hand: a retrospective study of 173 cases.

In this retrospective study we aimed to analyse the risk factors for complications after different methods of distal interphalangeal arthrodesis in the hand. Forty-four per cent were treated with K-wire/cerclage fixation, 46% with X-fuse® implants (Stryker GmbH, Selzach, Switzerland) and 10% with headless compression screws (HBS®-screw, KLS Martin Group, Tuttlingen, Germany). The median follow-up was 16 weeks (range 6-224). The overall complication incidence was 44% (minor complications 29% and major 15%). The logistic regression showed that osteoarthritis, revisional arthrodesis and smoking had a negative impact on the total complication incidence. A Cox-regression analysis showed that HBS®-screw arthrodesis was associated with a significantly lower incidence of major complications compared with K-wire/cerclage and X-Fuse®-arthrodesis. Revisional arthrodesis was five times more frequently connected with major complications than primary surgery. Smokers were three times more likely to experience major complications than non-smokers. We conclude that arthrodesis of the distal interphalangeal joint often leads to complications. Risk factors must be kept in mind.Level of evidence: III.

Oncological Safety and Recurrence in the Surgical Treatment of Atypical Fibroxanthoma and Pleomorphic Dermal Sarcoma of the Scalp.

Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are two distinct designations for a rare dermal sarcoma entity. These tumors arise predominantly in the sun-damaged skin of elderly patients. Although both AFX and PDS have a similar clinical presentation and nearly identical genetic features, they significantly differ in prognosis. Here we present a retrospective single-center chart review analyzing the outcomes of patients treated for dermal sarcoma. The radicality of the tumor-resection extent and soft-tissue reconstructive options were assessed. Patients between January 2010 and August 2021 were included. We recorded resection margins, tumor recurrence, overall survival, number of operations until complete tumor resection, and reconstructive procedures; any complications were recorded. Furthermore, we analyzed a subgroup of patients with satellite metastases. A total of 32 patients met the inclusion criteria (30 male, 2 female, median age of 77.5 years (interquartile range (IQR) 74-81)). Histopathology revealed AFX in 14 patients and PDS in 18 patients. Margin-free resection was achieved in 31 cases, and 27 patients were remission free over the reported period. The local recurrence rate was 5, and distant metastasis was detected in four cases. Of all the PDS cases, nine presented with satellite metastasis. No AFX had satellite metastases. Due to their rarity, managing these tumors requires an interdisciplinary setting in a specialized sarcoma center.

Age-related outcome of facial reanimation surgery using cross face nerve graft and gracilis free functional muscle transfer-A retrospective cohort study.

BACKGROUND: Free functional muscle transfer has become the criterion standard for the treatment of long-standing flaccid facial paralysis. Clinical experience suggests that a two-stage approach using a cross-face nerve graft (CFNG) as a donor nerve for free functional muscle transfers (FFMT) is less successful in older patients when compared to the pediatric population. However, clear data and scientific evidence are still rare. This study examines the age-related outcome of CFNG-driven FFMT. METHODS: Twenty-eight patients with a mean age of 20.73 years (ranging 5-51 years) who received two-stage facial reanimation with CFNG-driven gracilis FFMT at our institution from 1998 to 2019 were included. The ipsilateral sural nerve was used as CFNG. After 12 months, the ipsilateral gracilis muscle was used as FFMT. Patients were distributed equally into three cohorts according to their age. We assessed facial symmetry before and after facial reanimation measuring the angle between the interpupillary and the intermodiolar line (pupillo-modiolar angle). Additionally, the commissure height was measured using the Emotrics software. RESULTS: The mean follow-up of the pediatric, young adults and the middle-aged cohort was 29.5 ± 7.3, 24.9 ± 6.3, and 25.5 ± 12.4 months, respectively. One patient suffered flap loss due to flap ischemia. Four patients suffered insufficient innervation of the FFMT. Otherwise no major complication occurred. The likelihood of successful innervation of the FFMT was significantly higher in patients younger than 31 years (100% vs. 50%; p = .003). Smiling facial symmetry (pupillo-modiolar angle) significantly improved in the pediatric cohort (5-16 years; 8.68° ± 0.69° to 1.48° ± 0.67°; p < .001) and the young adults' cohort (17-30 years; 11.55° ± 1.95° to 4.62° ± 1.08°; p = .005), but improved only slightly in the middle-aged cohort (31-51 years; 11.77° ± 1.16° to 9.4° ± 1.8° p = .27). The postoperative smiling symmetry showed a significant correlation with increasing age (r = .62, p < .001). The smiling commissure height deviation significantly improved in the pediatric cohort (5-16 years; 6.5-2.3 mm; p = .006) and the postoperative result was significantly better than the middle-aged group (31-51 years; 2.3 vs. 7.5 mm; p = .02). CONCLUSIONS: The outcome of CFNG-driven gracilis FFMT is age-related. Static as well as dynamic facial symmetry after two-stage facial reanimation was best in the pediatric and young adult population. For older patients, other approaches like the nerve-to-masseter-driven FFMT should be considered.