[Robot-assisted Microsurgery in Lower Extremity Reconstruction]. / Roboter-assistierte Mikrochirurgie in der Rekonstruktion der unteren Extremität.

BACKGROUND: In recent years, various robotic systems specifically designed for microsurgical tasks have been developed and approved. There is not much evidence for these systems to date. In our study, we examined the use of robot-assisted microsurgery in the reconstruction of the lower extremity. PATIENTS/MATERIAL AND METHODS: Data was prospectively collected between February and November 2023. The Symani robotic system was used in 42 robot-assisted microsurgical procedures on the lower extremity, and the results were evaluated and documented. RESULTS: The average age of the patients was 57±18 years. A total of 39 free flap reconstructions (95%), one lymphatic surgical procedure (3%) and two nerve transfers (5%) were performed. In total, 46 anastomoses and coaptations were carried out. This included six arterial end-to-end anastomoses (11%), seven arterial end-to-side anastomoses (13%), 36 venous end-to-end anastomoses (65%), two lymphovenous anastomoses (4%), and five epineural coaptations in the context of nerve transfers (9%). Arterial end-to-end anastomoses took an average of 26±12 minutes, and arterial end-to-side anastomoses took 42±21 minutes. The venous anastomoses took an average of 33±12 minutes. Epineural coaptations took an average of 24±13 minutes. In no procedure was there a need for a conversion to conventional hand suturing. There were two arterial thromboses (5%), one of which was successfully revised to save the flap. One total flap loss occurred, but there were no partial flap losses. CONCLUSION: Using the Symani robotic system for microsurgical reconstruction of the lower extremity, we were able to demonstrate results that are comparable to conventional microsurgery.

Patient characteristics and disease spectrum in a German vascular anomalies center.

BACKGROUND: Vascular malformations are rare diseases that should be treated in dedicated vascular anomaly centers (VAC). There is only a small amount of data on the diagnostic and therapeutic handling of these patients, before they are referred to a VAC. PURPOSE: To demonstrate the disease-specific patient characteristics in a German VAC, which are required to determine diagnostic and therapeutic steps. MATERIAL AND METHODS: In a retrospective study, all patients who were treated in the VAC from April 2014 until August 2021 were identified. In total, 593 patients were included in this study. RESULTS: Almost all patients had previously consulted a physician (591/593, 99.7%). A mean of two different physicians had been consulted (range 0-10). Patients with more complex, syndromal vascular malformations had significantly more previous appointments (P = 0.0018). In only 44% (261/593) of patients, the referral diagnosis was made correctly. Most patients had been previously treated for their vascular anomaly: pharmacotherapy (n = 130; 21.9%), compression garments (n = 141; 23.8%), surgical resection (n = 80; 17.3%) and sclerotherapy (n = 68; 11.5%). Fifty-two patients who had been falsely diagnosed had also received therapy prior to their referral to the VAC (8.8%). Most patients received an ultrasound examination in the VAC (n = 464; 78.2%). Most frequently, compression therapy was prescribed (n = 256; 43.2%), followed by sclerotherapy (n = 175, 29.5%) and pharmacotherapy (n = 55; 9.3%). CONCLUSION: Patients suffering from vascular anomalies often go through a complicated scheduling with numerous outpatient appointments and have a high risk of misdiagnosis and mistreatment prolonging the medical condition. Therefore, patients with vascular anomalies should be treated in a dedicated vascular anomaly center.

Scalp Reconstruction Using the Latissimus Dorsi Free Flap: A 12-Year Experience.

BACKGROUND: Complex scalp defects are regularly reconstructed using microvascular tissue transfer. The latissimus dorsi free flap is one of the workhorse flaps used in scalp reconstruction. These cases necessitate, particularly in the elderly, a close cooperation between plastic surgeons and neurosurgeons. The purpose of this study was to evaluate the suitability of the latissimus dorsi free flap for complex scalp reconstructions and to analyze potential risk factors. METHODS: A retrospective study identified 43 patients undergoing complex scalp reconstruction using a latissimus dorsi free flap at our department between 2010 and 2022. RESULTS: The mean patient age was 61 ± 18 years. Defects were mostly caused by oncologic tumor resections (n = 23; 55%), exposure to a cranioplasty (n = 10; 23%) or infection (n = 4; 9%). The most frequent recipient vessels were the superficial temporal artery (n = 28; 65%), external carotid artery (n = 12; 28%) and the venae comitantes (n = 28; 65%), external jugular vein (n = 6; 14%). The reconstructive success rate was 97.7%. There was one total flap loss (2%). Partial flap loss occurred in five cases (12%). Follow-up was 8 ± 12 months. Major complications were seen in 13 cases, resulting in a revision rate of 26%. Multivariate logistic regression identified active tobacco use as the only risk factor for major complications (odds ratio 8.9; p = 0.04). CONCLUSION: Reconstruction of complex scalp defects using the latissimus dorsi free flap yielded high success rates. Among the potential risk factors, active tobacco use seems to affect the outcome of complex scalp reconstructions.

Enzymatic Debridement in Geriatric Burn Patients-A Reliable Option for Selective Eschar Removal.

The treatment of geriatric burn patients represents a major challenge in burn care. The objective of this study was to evaluate the efficacy of enzymatic debridement (ED) in geriatric burn patients. Adult patients who received ED for treatment of mixed pattern and full thickness burns (August 2017-October 2022) were included in this study and grouped in the younger (18-65 years) and geriatric (≥65 years) groups. Primary outcome was a necessity of surgery subsequent to ED. Both groups (patient characteristics, surgical and non-surgical treatment) were compared. Multiple logistic and linear regression models were used to identify the effect of age on the outcomes. A total of 169 patients were included (younger group: 135 patients, geriatric group: 34 patients). The burn size as indicated by %TBSA (24.2 ± 20.4% vs. 26.8 ± 17.1%, p = 0.499) was similar in both groups. The ASA (2.5 ± 1.1 vs. 3.4 ± 1.1, p < 0.001) and ABSI scores (6.1 ± 2.8 vs. 8.6 ± 2.3, p < 0.001) were significantly higher in the geriatric group. The %TBSA treated with ED (5.4 ± 5.0% vs. 4.4 ± 4.3%, p = 0.245) were similar in both groups. The necessity of additional surgical interventions (63.0 % vs. 58.8 %, p = 0.763) and the wound size debrided and grafted (2.9 ± 3.5% vs. 2.2 ± 2.1%; p = 0.301) were similar in both groups. Regression models yielded that age did not have an effect on efficacy of ED. We showed that ED is reliable and safe to use in geriatric patients. Age did not have a significant influence on the surgical outcomes of ED. In both groups, the size of the grafted area was reduced and, in many patients, surgery was avoided completely.

A Retrospective Matched-Pair Analysis of Long-term Outcomes after Successful Lower Extremity Free Flap Salvage.

BACKGROUND: Pedicle occlusion with total free flap loss after microvascular lower extremity reconstruction is a considerably rare yet devastating complication. Fortunately, in the majority of cases, emergency salvage takebacks of compromised free flaps are initiated in a timely manner. In this report, we present our analysis of long-term outcomes following transient vascular compromise mitigated through successful free flap salvage in the lower extremity. METHODS: We performed a single-center retrospective matched-pair analysis of 46 patients with lower extremity free flap reconstructions. Cases underwent successful revisions of microvascular compromise (n = 23), whereas controls had uneventful postoperative courses (n = 23). Patient-reported outcome questionnaires and physical evaluations were used to assess general quality of life, functional outcomes, and cosmesis (Lower Extremity Functional Scale [LEFS], Lower Limb Outcomes Questionnaire [LLOQ], Short Form 36 (SF-36), Vancouver Scar Scale [VSS]). The mean follow-up time was 4.4 years. RESULTS: The health-related quality of life assessed by the SF-36 did not differ significantly between both groups in any of the subscales (p ≥ 0.15 for all subscales). Functional outcomes did not show significant differences between both groups according to the LEFS (p = 0.78) and LLOQ (p = 0.45). The overall scar appearance assessed by the VSS showed significantly poorer cosmesis in the re-exploration group (p = 0.014). CONCLUSION: Salvage of compromised free flaps in the lower extremity yields similar long-term outcomes compared to noncompromised free flaps with regard to function and quality of life. However, free flap revisions may lead to impaired scar formation. This study provides further evidence that the opportunity for urgent re-exploration is indispensable.

Performance of a vascular anomaly center: a retrospective analysis of 461 cases over seven years.

BACKGROUND: Vascular malformations are rare diseases that are best managed in multidisciplinary vascular anomaly centers (VAC). So far, there are few published data on the logistic structure, patient allotment, and internal workflow in an interdisciplinary VAC. PURPOSE: To demonstrate the referral structure and patient allotment in a European VAC. MATERIAL AND METHODS: A retrospective cohort study was conducted. All patients treated in the VAC since its establishment in April 2014 until June 2020 were identified. A total of 461 patients were included in this study. RESULTS: Most often, a venous malformation was diagnosed (49.9%), followed by arteriovenous malformations (8.7%) and syndromal vascular malformations (8.2%). Only 45.1% of referral diagnoses were correct. Of referrals, 35.1% were internal on-campus references, 28.0% were external references through physicians in private practice, and 19.7% came via external cooperating hospitals. Of the patients, 17.1% were self-admissions without a referral. CONCLUSION: The most important referring clinics are internal medicine, pediatric, and vascular surgery. A substantial proportion of referrals came from private practices. Recruiting these cooperation partners should be considered a high priority when establishing a new VAC. The rate of misdiagnosis is high, and more education of fellow clinicians is urgently needed. Therefore, patients with vascular malformations should be referred to and treated in dedicated centers for vascular anomalies.

Long-term diazepam treatment enhances microglial spine engulfment and impairs cognitive performance via the mitochondrial 18 kDa translocator protein (TSPO).

Benzodiazepines are widely administered drugs to treat anxiety and insomnia. In addition to tolerance development and abuse liability, their chronic use may cause cognitive impairment and increase the risk for dementia. However, the mechanism by which benzodiazepines might contribute to persistent cognitive decline remains unknown. Here we report that diazepam, a widely prescribed benzodiazepine, impairs the structural plasticity of dendritic spines, causing cognitive impairment in mice. Diazepam induces these deficits via the mitochondrial 18 kDa translocator protein (TSPO), rather than classical γ-aminobutyric acid type A receptors, which alters microglial morphology, and phagocytosis of synaptic material. Collectively, our findings demonstrate a mechanism by which TSPO ligands alter synaptic plasticity and, as a consequence, cause cognitive impairment.

Interdisciplinary management of peripheral arteriovenous malformations: review of the literature and current proceedings.

Arteriovenous malformations (AVMs) are a rare congenital vascular disorder. They represent a fast-flow vascular malformation. Clinically, AVMs present a heterogenous expression and can affect every part of the body. Here, we will solely focus on extracranial AVMs. Generally, AVMs progress with the patient's age. Patients often suffer from pulsation, skin discoloration, pain, ulceration, bleeding, and disfigurement. Diagnostic tools include color-coded duplex sonography, MRI and CT imaging, as well as the clinical examination. 4D dynamic perfusion-computed tomography may help in the interventional planning. Digital subtraction angiography is required during interventional therapy. AVMs pose a great challenge to the treating physician. The therapy of this rare disease should be managed in an interdisciplinary center for vascular malformations. It consists of conservative measures, such as compression garments and pain medication, transcatheter or, more rarely, percutanous embolization, and surgical resection. In smaller, localized lesions, resection with primary wound closure may be feasible, whereas extensive AVMs regularly require the reconstruction of the resulting soft tissue defect and possibly affected functional structures by means of free tissue transfer. In the interdisciplinary setting required for an appropriate treatment of AVMs, extensive knowledge of the various therapies, including those from different specialties, is necessary. Therefore, this article aims to provide an overview over both the interventional and surgical therapeutic options.

Molecular diagnostics helps to identify distinct subgroups of spinal astrocytomas.

Primary spinal cord astrocytomas are rare, hence few data exist about the prognostic significance of molecular markers. Here we analyze a panel of molecular alterations in association with the clinical course. Histology and genome sequencing was performed in 26 spinal astrocytomas operated upon between 2000 and 2020. Next-generation DNA/RNA sequencing (NGS) and methylome analysis were performed to determine molecular alterations. Histology and NGS allowed the distinction of 5 tumor subgroups: glioblastoma IDH wildtype (GBM); diffuse midline glioma H3 K27M mutated (DMG-H3); high-grade astrocytoma with piloid features (HAP); diffuse astrocytoma IDH mutated (DA), diffuse leptomeningeal glioneural tumors (DGLN) and pilocytic astrocytoma (PA). Within all tumor entities GBM (median OS: 5.5 months), DMG-H3 (median OS: 13 months) and HAP (median OS: 8 months) showed a fatal prognosis. DMG-H3 tend to emerge in adolescence whereas GBM and HAP develop in the elderly. HAP are characterized by CDKN2A/B deletion and ATRX mutation. 50% of PA tumors carried a mutation in the PIK3CA gene which is seemingly associated with better outcome (median OS: PIK3CA mutated 107.5 vs 45.5 months in wildtype PA). This exploratory molecular profiling of spinal cord astrocytomas allows to identify distinct subgroups by combining molecular markers and histomorphology. DMG-H3 tend to develop in adolescence with a similar dismal prognosis like GBM and HAP in the elderly. We here describe spinal HAP with a distinct molecular profile for the first time.

Fibroadipose Vascular Anomaly of the Upper Extremity: Case Report of Extensive Resection and Secondary Tendon Transfer.

ABSTRACT: Alomari and colleagues described in 2014 for the first time a distinct combination of vascular malformation, fibrofatty muscular infiltration and contracture which was termed fibroadipose vascular anomaly (FAVA) (J Pediatr Orthoped 34, 109-117 (2014). So far only few publications (J Pediatr Orthoped (2014) 34, 109-117; J Hand Surg (2020). 45, 68.e1, 68.e13; Ann Vasc Dis (2014) 7, 316-319; Pediatr Radiol 46, 1179-1186 (2016)) concerning this newly described disease have been published, covering only a limited number of cases. We present a case of a 19-year-old male patient suffering from a FAVA of the proximal forearm with a severe contracture of the infiltrated flexor musculature. Upon surgery, we observed infiltration of the ulnar nerve. We were able to successfully resect the vascular malformation. Secondary tendon transfer was performed after extensive resection of the flexor musculature.FAVA presents a differential diagnosis in patients with solid growth of the upper or lower extremity and contracture of the involved extremity. We conclude that patients suffering from FAVA of the upper extremity should be referred to a center specialized in oncologic extremity surgery and reconstructive hand and microsurgery.

A surprising diagnosis in a young patient with intermittent claudication: Symptomatic isolated external iliac artery aneurysm associated with cystic media necrosis.

Aneurysms of the external iliac artery are extremely rare. We present a case of a middle-aged male patient with calf claudication owing to peripheral arterial embolism on the basis of a thrombosed true aneurysm of the external iliac artery caused by cystic media necrosis. Vascular imaging established the diagnosis and we proceeded to removal of the aneurysm via open repair, with excellent surgical and clinical results.

Microsurgical Technique of Locoregional Injection into the Hepatic Artery in Tumor-Bearing Mice.

BACKGROUND: Intraarterial injection into the hepatic artery represents an important route for locoregional administration for the treatment of hepatic tumors. In the present work, we describe microsurgical methodology for injection into the hepatic artery in mice. The technique was recently used for analysis of the phenomenon of endothelial capture in liver tumors. METHODS: Two different models of hepatic tumors in C57BL/6 mice were used. Tumors were induced by intrahepatic cell inoculation. The preferential blood supply of tumors was studied using blocking of bioavailability of nontumoral endothelial epitope and the subsequent injection of fluorescent endothelium-specific antibody. The selective intraarterial injection of labeled antibody was performed in tumor-bearing mice. The procedure addressed variations of vascular anatomy of the hepatic artery in mice and used direct intraarterial injection with dispensable catheterization. RESULTS: Both experimental tumor models showed preferential blood supply from the hepatic artery. The technique of hepatic arterial injection was adapted and performed according to two major anatomic variations of the hepatic artery. Using this technique, the selective enrichment of labeled antibody to tumor and liver blood vessels, which were perfused during the first intravascular passage, was demonstrated. CONCLUSIONS: The experimental hepatic arterial injection in mice is a feasible but demanding microsurgical procedure. The choice of subsequent operation steps is dependent on the vascular anatomy of the hepatic artery which has two major variations in mice.

Evaluation of perfusion by near-infrared fluorescence imaging in late pedicle obstruction of a parascapular flap to the lower extremity: A case report.

Late free flap failures due to pedicle obstruction are rare adverse events. The purpose of this report is to present a case in which the near-infrared indocyanine green video angiography (ICG-NIR-VA) was used to evaluate the perfusion in a compromised fasciocutaneous flap in the late postoperative period. A 55-year-old male patient, who initially suffered from an open tibial fracture, developed concurrent osteomyelitis with fistulae of the proximal tibia requiring excision. Reconstruction was achieved using a parascapular flap of 25 × 8 cm, anastomosed to an arterio-venous (AV) Loop in the adductor canal. On the 2nd postoperative day the patient developed a thrombosis of the AV-Loop. After thrombectomy, the postoperative course was uneventful. Seven weeks postoperatively the patient presented with a mottled, partially bluish and cold flap. Anticoagulation prophylaxis was stopped 2 days earlier. Angiography confirmed a thrombus in the arterial pedicle leading to flap ischemia. Near infrared guided fluorescence imaging revealed a delayed recapillarization of the proximal part of the flap closest to the vascular pedicle, albeit flap overall perfusion remained intact. Thus, no surgical intervention was undertaken. However, anticoagulation and prostaglandin therapy was initiated and the flap was salvaged. Genetic analysis uncovered a polymorphism in the prothrombin genes. The flap remained viable and without further complications until the last follow-up visit at 36 weeks after microsurgical reconstruction. The patient was fully mobilized with complete return to function. Near-infrared guided fluorescence imaging may be a viable tool for the assessment of late fasciocutaneous free flap complications and guide the decision-making process.

Phenomenon of Endothelial Antibody Capture: Principles and Potential for Locoregional Targeting of Hepatic Tumors.

The systemic drug circulation represents a source of adverse effects during tumor targeting. We studied the binding efficacy of endothelium-specific antibodies after a very short contact with an antigen target, along with assessing the intravascular capture and targeting potential of these antibodies after locoregional injection. Fast-binding anti-CD 146 (clone ME-9F1) and anti-CD31 (clone 390) antibodies were selected based on histological analysis of their binding activity. The efficacy of antibody capture by hepatic endothelium under different conditions was analyzed using an isolated liver perfusion model. The local enrichment of R-phycoerythrin and 125 I-conjugated antibody was studied in vivo in two hepatic tumor models using biodistribution, scintigraphic imaging, and fluorescence microscopy. Upon injection into the tumor-feeding artery, the antibody was immediately captured in the microvasculature during the first passage. At doses not exceeding the saturation level of endothelial epitopes, the capture efficacy was almost 90%. We showed that the efficacy of endothelial capture is controlled by factors such as antibody affinity, number of binding sites on the endothelium, and microvascular flow rate. The targeting potential of endothelial capture was experimentally proven in vivo using scintigraphic imaging and biodistribution analysis after locoregional intra-arterial injection of 125 I-labeled antibodies in hepatic tumor models. Conclusion: The unique phenomenon of endothelial capture can broadly prevent systemic circulation of the antibody or antibody-drug conjugates applied by intravascular injection and may have specific relevance for targeting of hepatic tumors.

Development of a competency-based formative progress test with student-generated MCQs: Results from a multi-centre pilot study.

INTRODUCTION: Progress tests provide students feedback on their level of proficiency over the course of their medical studies. Peer-assisted learning and competency-based education have become increasingly important in medical education. Although progress tests have been proven to be useful as a longitudinal feedback instrument, there are currently no progress tests that have been created in cooperation with students or that focus on competency in medical education. In this study, we investigated the extent to which students can be included in the development of a progress test and demonstrated that aspects of knowledge related to competency can be represented on a competency-based progress test. METHODS: A two-dimensional blueprint for 144 multiple-choice questions (MCQs) covering groups of medical subjects and groups of competency areas was generated by three expert groups for developing the competency-based progress test. A total of 31 students from seven medical schools in Germany actively participated in this exercise. After completing an intensive and comprehensive training programme, the students generated and reviewed the test questions for the competency-based progress test using a separate platform of the ItemManagementSystem (IMS). This test was administered as a formative test to 469 students in a pilot study in November 2013 at eight medical schools in Germany. The scores were analysed for the overall test and differentiated according to the subject groups and competency areas. RESULTS: A pool of more than 200 MCQs was compiled by the students for pilot use, of which 118 student-generated MCQs were used in the progress test. University instructors supplemented this pool with 26 MCQs, which primarily addressed the area of scientific skills. The post-review showed that student-generated MCQs were of high quality with regard to test statistic criteria and content. Overall, the progress test displayed a very high reliability. When the academic years were compared, the progress test mapped out over the course of study not only by the overall test but also in terms of the subject groups and competency areas. OUTLOOK: Further development in cooperation with students will be continued. Focus will be on compiling additional questions and test formats that can represent competency at a higher skill level, such as key feature questions, situational judgement test questions and OSCE. In addition, the feedback formats will be successively expanded. The intention is also to offer the formative competency-based progress test online.

Error monitoring is altered in musician's dystonia: evidence from ERP-based studies.

Musician's dystonia (MD) is a task-specific movement disorder characterized by a loss of voluntary motor control in highly trained movements like piano playing. Its underlying pathophysiology is defined by deficient functioning of neural pathways at different levels of the central nervous system. However, a few studies have examined the brain responses associated with executive functions such as error monitoring in MD. We recorded the electroencephalogram (EEG) in professional pianists during the performance of memorized music sequences at fast tempi. Event-related potentials (ERPs) locked to pitch errors were investigated in MD and a control group. In MD patients, significantly larger error-related brain responses before and following errors were observed as compared with healthy pianists. Our results suggest that in MD, the generalized degraded neural activity at all levels of the central nervous system is manifested in specific neural correlates of the executive functions that monitor an overlearned sensorimotor performance.

EEG oscillatory patterns are associated with error prediction during music performance and are altered in musician's dystonia.

Skilled performance requires the ability to monitor ongoing behavior, detect errors in advance and modify the performance accordingly. The acquisition of fast predictive mechanisms might be possible due to the extensive training characterizing expertise performance. Recent EEG studies on piano performance reported a negative event-related potential (ERP) triggered in the ACC 70 ms before performance errors (pitch errors due to incorrect keypress). This ERP component, termed pre-error related negativity (pre-ERN), was assumed to reflect processes of error detection in advance. However, some questions remained to be addressed: (i) Does the electrophysiological marker prior to errors reflect an error signal itself or is it related instead to the implementation of control mechanisms? (ii) Does the posterior frontomedial cortex (pFMC, including ACC) interact with other brain regions to implement control adjustments following motor prediction of an upcoming error? (iii) Can we gain insight into the electrophysiological correlates of error prediction and control by assessing the local neuronal synchronization and phase interaction among neuronal populations? (iv) Finally, are error detection and control mechanisms defective in pianists with musician's dystonia (MD), a focal task-specific dystonia resulting from dysfunction of the basal ganglia-thalamic-frontal circuits? Consequently, we investigated the EEG oscillatory and phase synchronization correlates of error detection and control during piano performances in healthy pianists and in a group of pianists with MD. In healthy pianists, the main outcomes were increased pre-error theta and beta band oscillations over the pFMC and 13-15 Hz phase synchronization, between the pFMC and the right lateral prefrontal cortex, which predicted corrective mechanisms. In MD patients, the pattern of phase synchronization appeared in a different frequency band (6-8 Hz) and correlated with the severity of the disorder. The present findings shed new light on the neural mechanisms, which might implement motor prediction by means of forward control processes, as they function in healthy pianists and in their altered form in patients with MD.