Wound Healing Disorders Research Articles

Blood-saving dissection with monopolar tungsten needle electrodes and Teflon-coated spatula electrodes in tumor orthopedics

IntroductionResection of musculoskeletal tumors and reconstruction with tumor endoprostheses often results in blood loss requiring transfusion of blood products. We assessed the blood-saving potential of using monopolar tungsten needle electrodes and polytetrafluoroethylene (PTFE)-coated spatula electrodes (intervention) compared with conventional dissection with sharp instruments and coagulation with uncoated steel electrodes (control).MethodsWe retrospectively analyzed data of 132 patients (79 interventions, 53 controls) undergoing surgery by one single experienced surgeon in our tertiary referral center between 2012 and 2021.ResultsIntraoperative blood loss in the intervention group was reduced by 29% [median (IQR): 700 (400–1200) vs 500 (200–700) ml; p = 0.0043]. Postoperative wound drainage decreased by 41% [median (IQR): 1230 (668–2041) vs 730 (450–1354) ml; p = 0.0080]. Additionally, patients in need of PRBCs during surgery declined from 43% to 15% (23/53 vs 12/79; p = 0.0005), while the transfusion rate after surgery did not change notably. The number of patients in need of revision surgery due to wound healing disorders was low in both groups (control group: 4/53 vs intervention group: 4/79). Only one patient in the control group and two patients in the intervention group underwent revision surgery due to hemorrhage. Baseline characteristics were similar between groups (sex, Charlson Comorbidity score, tumor entity).ConclusionDissection with tungsten needle electrodes and PTFE-coated spatula electrodes appears an effective surgical blood-saving measure without increased risk of wound healing disorders.Level of evidenceIII, retrospective comparative study.Clinical trial registration. The study was registered at ClinicalTrials.gov. Identifier: NCT05164809.

574 The Impact of Age on Wound Healing Progression in Burns

Abstract Introduction Increasing incidences of wound healing disorders are a growing problem in our aging society. Moreover, the survival rate of the elderly is diminished when it comes to extensive high-grade burn injuries. Here, we characterized the systemic and local reactions towards burn injuries in young, middle aged and aged rats. Additionally, we provide a comparison in wound healing progression between burn wounds and full-thickness wounds of the same sizes. Methods For this study, 54 male Wistar rats from three different age groups (11; 27; and 56 weeks) either received high-grade contact burns, full-thickness skin wounds (2x2 wounds, Ø 10 mm each) or served as unwounded controls. Throughout the study regular wound documentation and non-invasive imaging methods were performed. Blood was sampled from the tail vein to detect differences in plasma cytokine concentrations. Moreover, body weight and food intake were measured daily. On the final study day (day 7), tissue biopsies were collected from the wound and control areas and were analyzed on a histological and molecular level. Mainly inflammatory markers (interleukins, TGFb, TNFa etc.) and markers for tissue perfusion (VEGFa, HIF1a) were quantified by qPCR. Repeated measures analysis of variance was performed to compare the means among groups. Results We found that epidermal thickness of unwounded skin declined with age and was lowest in 56-weeks-old rats. On day 4 after wounding, tissue perfusion was significantly impaired in 27- and 56-weeks-old rats compared to 11-weeks-old rats (p < 0.001). Histological scores for the immune response showed an age-dependent effect in both burns and excisional wounds. Neutrophil and lymphocyte counts were highest in the 27-weeks-old rats (11 weeks vs. 27 weeks: p < 0.001). Eosinophil counts, however, were significantly increased in burn wounds compared to excisional wounds (p = 0.013), regardless of age. We did not detect any age-dependent effects in wound sizes on the final day, nor in the animals’ weight loss after wounding. Conclusions Although there are significant age-related differences in the thickness of the epidermis, the angiogenic potential of the skin and the local immune response, these differences do not seem to affect healing. It is reasonable to assume that decreased wound healing progression occurs only when additional factors, such as impaired perfusion, diabetes etc are involved. Applicability of Research to Practice We believe the precise knowledge of processes involved in wound healing is crucial for the development of new therapeutic strategies and to support healing after burns. Our results might challenge the paradigm of impaired healing in aged individuals and draw attention to the necessity to dig for other influential factors. However, as skin morphology and healing dynamics differ between rodents and humans, we plan to implement a translational approach using human abdominal skin flaps of donors from different age groups.

Complications arising from aesthetic surgery procedures in foreign countries and Switzerland

Cosmetic surgery tourism has increased in popularity in recent years, with arising complications and post-operative follow-up care often managed in the client's home country, thereby burdening the Swiss health care system. We retrospectively reviewed patients with complications after cosmetic surgeries abroad and in Switzerland who were treated at the University Hospital Zurich between 2015 and 2019. Data were collected from medical records and reviewed for patient characteristics, procedures, complications, and treatment modalities. A total of 228 patients (207 females and 21 males) were identified with female mean age of 40.9±12.0 years and male mean age of 34.3±8.9 years. Most complications were observed for procedures performed in Europe (69%) with only thirty-six patients (16%) experiencing complications due to a procedure undertaken in Switzerland. Breast surgery was the most frequently performed procedure (60%), followed by body contouring (17%) and facial surgery (12%). The most common complications occurring after surgeries abroad were pain and discomfort (19%) as well as aesthetic dissatisfaction (18%), followed by wound breakdown (14%) and infection (11%). Most patients (76%) were treated as outpatients and the treatment of all patients over the observed period cost the healthcare system $ 795,574. There is an ongoing trend of cosmetic surgery tourism leading to an increasing number of patients with complications requiring aftercare in Switzerland. In contrast to previous research, more men are seeking cosmetic surgery abroad and the most common complications, such as wound healing disorders and infection, descreased in favor of aethetic dissatisfaction, possibly indicating ameliorated patient aftercare abroad.

Comparison of Two Umbilicoplasty Techniques in 72 Patients after Breast Reconstruction with a Free DIEP Flap

The appearance of the umbilicus after DIEP flap surgery or abdominoplasty plays an important role in aesthetic perception (1). Although the umbilicus has no function, there is no doubt about the importance of its shape for the self-esteem of patients, especially after breast cancer (2). In the present study, we compared two of the preferred techniques described in the literature on 72 patients in terms of aesthetic outcome, complications and sensitivity: the caudal flap (domed shape) and the oval shape of the umbilicus. Seventy-two patients who underwent a DIEP flap for breast reconstruction between January 2016 and July 2018 were retrospectively included in this study. Two techniques for umbilical reconstruction were compared: the transverse oval shape of the umbilicus and umbilicoplasty using a caudal flap, which results in a dome shape of the umbilicus. To compare the aesthetic results, an evaluation by the patients and an assessment by three independent plastic surgeons were carried out at least 6 months postoperatively. Patients and surgeons were asked to rate the general appearance of the umbilicus, including scarring and shape, on a scale from 1 to 6 (1=very good, 2=good, 3=fair, 4=sufficient, 5=poor, 6=insufficient). Furthermore, the occurrence of wound healing disorders was examined, and patients were asked about the sensitivity of the umbilicus. Both techniques showed similar degrees of aesthetic satisfaction (p=0,49) as part of the patients' self-assessment. The plastic surgeons gave the caudal flap technique a significantly better rating than the umbilicus with a transverse oval shape (p=0,042). More wound healing disorders occurred in the caudal lobule (11,1%) compared with the transverse oval umbilicus. However, this was not significant (p=0,16). A surgical revision was not necessary. The caudal flap umbilicus showed a tendency to improved sensitivity (60 vs. 45%), but this was not significant (p=0,19). Patient satisfaction showed similar results for the two methods of umbilicoplasty. On average, both techniques were given a good rating for their results. However, surgeons rated the caudal flap umbilicoplasty as more aesthetically pleasing.

Human In Vitro Skin Models for Wound Healing and Wound Healing Disorders.

Skin wound healing is essential to health and survival. Consequently, high amounts of research effort have been put into investigating the cellular and molecular components involved in the wound healing process. The use of animal experiments has contributed greatly to the knowledge of wound healing, skin diseases, and the exploration of treatment options. However, in addition to ethical concerns, anatomical and physiological inter-species differences often influence the translatability of animal-based studies. Human in vitro skin models, which include essential cellular and structural components for wound healing analyses, would improve the translatability of results and reduce animal experiments during the preclinical evaluation of novel therapy approaches. In this review, we summarize in vitro approaches, which are used to study wound healing as well as wound healing-pathologies such as chronic wounds, keloids, and hypertrophic scars in a human setting.

Protein Interaction Network Analysis of β-catenin to Map its Crucial Interacting Genes using Systems Biology Approach

β-catenin (CTNNB1), a scaffold protein, plays a vital role in embryonic development, adult tissue homeostasis, neurodegenerative diseases, bone diseases, chronic obstructive pulmonary diseases, wound healing, and pigment disorders. β-catenin is the crucial component in the Wnt-signaling pathway. β-catenin levels in the cytosol balance the Wnt-signaling pathway. The activated Wnt-signaling pathway allows the accumulation of β-catenin in the nucleus and further act as a promoter to initiate transcription of several oncogenes responsible for carcinogenesis. In the present study, we have used a systems biology approach to map β-catenin interactors. Primary protein-protein interaction databases such as PubChem, CTD, and STITCH databases were used to collect all the experimentally valid β-catenin interactors and their subcellular location was traced using UniProtKB database. The interactome was constructed and analyzed by utilizing STRING and Cytoscape tools. MCODE, Cytoscape tool, was utilized to construct and analyze the sub-networks. Correlation between modular seed proteins and β-catenin was studied using UALCAN database. Functional enrichment analysis was done using DAVID database. Cytohubba, a Cytoscape tool was utilized to identify the top gene interactors of β-catenin. Further, the expression and gene ontology of each β-catenin gene interactor were analyzed using UALCAN and CleuGO tools. The analysis reveals β-catenin interactors, TP53, EP300, RPS27A, UBC, HDAC1, SRC, AKT1, EGFR, HSP90AA1, and CREBBP as the first top gene interactors. This study uses a systems biology-driven approach and successfully identifies and understands the biological roles of the top β-catenin interactors.

A prospective, randomized, single-blind study to compare two methods of treating cystic lesions in the jaw

The study aimed to assess the usefulness of a bovine bone substitute material in treating cystic lesions in the jaw with a maximum diameter of <4 cm. In this prospective, randomized, single-blind intervention study of 116 patients, 61 underwent cystectomy with a subsequent filling of the defect using a bovine xenograft, and 55 underwent cystectomy alone. Volumetric measurement of the cysts was performed preoperatively and 6 and 12 months postoperatively using the available digital volume tomography data sets. Follow-up appointments were made 14 days and 1, 3, 6, and 12 months postoperatively. Almost complete regeneration was seen in both treatment groups within 12 months, with no significant difference in absolute volume loss between the 2 groups (P=.521). Examination 14 days after surgery revealed a tendency for more wound healing disorders with the use of a bone substitute (P=.077). It was no longer possible to detect any further differences in later examinations. Using bovine bone substitute material has no radiologically measurable advantage over cystectomy alone without defect filling regarding bone regeneration. In addition, there was a tendency for more wound-healing disorders to occur in the bone substitute group.

Donor Site Defect Coverage of the Forearm with Dermal Substitute After Harvesting Radial Forearm Free Flap for Phalloplasty: Is MatriDerm® Worth the Effort?

An aesthetically and functionally pleasing phalloplasty is most commonly performed by a free radial forearm flap. However, the problem with donor site morbidity on the forearm remains unsolved. The aim of this study was to evaluate if the use of a dermal template such as MatriDerm® on the donor site significantly decreases the incidence of complications based on the Clavien–Dindo classification, such as wound healing disorders and reoperation rate, and if it could shortens the duration of hospital stay. A case series analysis was conducted at our institution. A total of 21 patients divided into two groups undergoing the phallic construction after the Gottlieb and Levine design in a single center underwent the donor site defect coverage either by MatriDerm® and split-thickness skin graft from the thigh or by full-thickness skin graft from the groin area. The use of MatriDerm® and split-thickness skin graft showed to have a statistically significant impact on the rate of complications (p = 0.008). Complications that were treated conservatively as well as that require surgical revision were significantly lower in the MatriDerm® group than in the full-thickness skin graft group (p = 0.002). Complications occurred not only at the forearm but also at the groin, where the full-thickness skin graft was harvested. The large dimension of the free radial forearm flap used for phalloplasty resulted in a significant donor site morbidity, leading to wound healing disorders, reoperations, and extended length of hospital stay. Therefore, we consider the use of dermal templates such as MatriDerm® as worth the additional effort and costs in this patient collective.

Clinical evaluation of vertebral body replacement of carbon fiber–reinforced polyetheretherketone in patients with tumor manifestation of the thoracic and lumbar spine

PurposeRadiolucent anterior and posterior implants by carbon fiber–reinforced polyetheretherketone (CFR PEEK) aim to improve treatment of primary and secondary tumors of the spine during the last years. The aim of this study was to evaluate clinical and radiological outcomes after dorsoventral instrumentation using a CFR PEEK implant in a cohort of patients representing clinical reality. MethodsA total of 25 patients with tumor manifestation of the thoracic and lumbar spine underwent vertebral body replacement (VBR) using an expandable CFR PEEK implant between January 2021 and January 2022. Patient outcome, complications, and radiographic follow-up were analyzed.ResultsA consecutive series aged 65.8 ± 14.7 (27.6–91.2) years were treated at 37 vertebrae of tumor manifestation, including two cases (8.0%) of primary tumor as well as 23 cases (92.0%) of spinal metastases. Overall, 26 cages covering a median of 1 level (1–4) were implanted. Duration of surgery was 134 ± 104 (65–576) min, with a blood loss of 792 ± 785 (100–4000) ml. No intraoperative cage revision was required. Surgical complications were reported in three (12.0%) cases including hemothorax in two cases (one intraoperative, one postoperative) and atrophic wound healing disorder in one case. In two cases (8.0%), revision surgery was performed (fracture of the adjacent tumorous vertebrae, progressive construct failure regarding cage subsidence). No implant failure was observed.ConclusionVBR using CFR PEEK cages represents a legitimate surgical strategy which opens a variety of improvements—especially in patients in need of postoperative radiotherapy of the spine and MRI-based follow-up examinations.

Engineered extracellular vesicles for ischemic stroke treatment

Engineered extracellular vesicles for ischemic stroke treatment

Seasonal Impact on Free Flap Surgery in Terms of Flap Loss and Wound Healing Disorders: A Retrospective Cohort Study of 158 Free Flaps.

(1) Background: Postoperative flap loss and wound healing disorders are severe complications after microsurgical free flap surgery. Despite multiple clinical observations, a possible influence of season and external temperature on outcome are largely missing. (2) Methods: Retrospectively, data were collected from 151 patients receiving microsurgical free flaps from March 2018 to August 2019. Patients were divided into two cohorts. The winter group includes all patients who underwent surgery from October 2018 to March 2019 and the summer group al those who underwent surgery from April 2018 to September 2018. Data included demographic information, pre-existing conditions, flap characteristics, and postoperative complications like flap losses and wound healing problems. External temperatures during the first 14 postoperative days were documented and the predictor of flap loss and wound healing disorders was detected. (3) Results: In the winter group (October-March; Ø 7.24 °C) 72 patients (46 female, 24 males; Ø 57.0 years) and in the summer group (April-September; Ø 18.79 °C) 81 patients (48 female, 33 males; Ø 56.0 years) received free flap surgery. There were no significant differences in demography (age: p = 0.593; gender: p = 0.419; BMI: p = 0.141). We found a significant increase in flap loss during summer (χ2(1) = 6.626; p = 0.010; V = 0.209) strengthened by logistic regression analysis (p = 0.037; Exp(B) = 9.655). Additionally higher average temperatures 14 days postoperatively represents another main driver (p = 0.023, Exp(B) = 1.161) for postoperative flap loss. (4) Conclusions: The data confirm a significantly higher postoperative flap loss in the summer group. This information may potentially contribute to optimization of perioperative management and planning of elective and semi-elective surgeries.

Gracilis muscle transposition in complex anorectal fistulas of diverse types and etiologies: long-term results of 60 cases

PurposeComplex fistulas often require several attempts at repair and continue to be a challenging task for the surgeon, but above all, a major burden for the affected patient. This study is aimed at evaluating the potential of gracilis muscle transposition (GMT) as a therapeutic option for complex fistulas of diverse etiologies.MethodsA retrospective study was conducted over a period of 16 years with a total of 60 patients (mean age 50 years). All were treated for complex fistula with GMT at St. Josef’s Hospital in Regensburg, Germany. Follow-up data were collected and analyzed using a prospective database and telephone interview. Success was defined as the absence of fistula.ResultsA total of 60 patients (44 women, 16 men; mean age 50 years, range 24–82 years) were reviewed from January 2005 to June 2021. Primary fistula closure after GMT was achieved in 20 patients (33%) and 19 required further interventions for final healing. Overall healing rate was 65%. Fistula type was heterogeneous, with a dominant subgroup of 35 rectovaginal fistulas. Etiologies of the fistulas were irradiation, abscesses, obstetric injury, and iatrogenic/unknown, and 98% of patients had had previous unsuccessful repair attempts (mean 3.6, range 1–15). In 60% of patients with a stoma (all patients had a stoma, 60/60), stoma closure could be performed after successful fistula closure. Mean follow-up after surgery was 35.9 months (range 1–187 months). No severe intraoperative complications occurred. Postoperative complications were observed in 25%: wound healing disorders (n = 6), gracilis necroses (n = 3), incisional hernia (n = 2), scar tissue pain (n = 2), suture granuloma (n = 1), and osteomyelitis (n = 1). In 3 patients, a second gracilis transposition was performed due to fistula recurrence (n = 2) or fecal incontinence (n = 1).ConclusionBased on the authors’ experience, GMT is an effective therapeutic option for the treatment of complex fistulas when other therapeutic attempts have failed and should therefore be considered earlier in the treatment process. It should be seen as the main but not the only step, as additional procedures may be required for complete closure in some cases.

Perioperative Safety of Bilateral Internal Thoracic Artery Coronary Bypass in Elderly.

The benefits of utilizing internal thoracic arteries (ITAs) in coronary bypass surgery are well-known. However, the safety of this practice in elderly patients needs to be proven. We studied all patients who are 75 years of age and older, who received at least one ITA graft while undergoing isolated, conventional (median sternotomy) coronary artery bypass graft surgery (CABG) between Jan 1st 2002 and Dec 31st 2020 (19 years). Emergent surgeries were excluded. Propensity score matching was used to reduce the patient selection effect. Study outcomes were 30-days mortality, and two sets of dependent intraoperative parameters and postoperative parameters. A total of 1855 patients undergoing CABG was included, of which 1114 received a single left (s)ITA and 741 received combined left and right (d)ITA grafts. 519 pairs were matched. The decision for sITA or dITA was made individually. Thirty-days mortality was low and similar in both groups (sITA 3.3%; dITA 2.9%, p = 0.859). The incidence of sternal wound healing disorder was higher after dITA (3.3 vs 6.9%; p 0.011), which had also a longer skin-to-skin operative time (181 vs 205 min; p 0.0001). Re-thoracotomy rates were similar (4.6 vs 6.2%; p = 0.340). There were no significant differences in other secondary parameters. harvesting both ITAs in elderly patients is safe and feasible. However, it increases the risk of sternal wound healing disorders. Long term benefit still needs to be proven.

Perfusion Changes in Perforator-Based Propeller Flaps

AbstractBackground To cover soft tissue defects, the perforator-based propeller flap offers the option to rotate healthy tissue into complex wounds. By rotating the flap, the perforator is torqued. As a result, perfusion changes are possible.Methods A retrospective data analysis of patients was done, who received a propeller flap to cover soft tissue defects of the lower extremity as well as a peri- and postoperative perfusion monitoring with a laser-Doppler-spectrophotometry system. Additionally, patient-specific data were collected.Results Seven patients were identified. Four patients experienced early complications, two epidermolysis of the distal flap areas, three wound healing disorders, and one partial flap necrosis. Intraoperative perfusion monitoring showed a decline of blood flow after incision of the flap, especially at distal flap site. In case of complications, there were prolonged blood flow declines up to the first postoperative day.Conclusion Torqueing the perforator by rotating the flap can cause an impairment in inflow and outflow. If the impairment is prolonged, perfusion-associated complications are possible. The identification of a viable perforator is particularly important. In addition, a conservative postoperative mobilization is necessary to compensate for the impaired and adapting outflow.

Itaconate promotes a wound resolving phenotype in pro-inflammatory macrophages

Pathological conditions associated with dysfunctional wound healing are characterized by impaired remodelling of extracellular matrix (ECM), increased macrophage infiltration, and chronic inflammation. Macrophages also play an important role in wound healing as they drive wound closure by secretion of molecules like transforming growth factor beta-1 (TGF-β). As the functions of macrophages are regulated by their metabolism, local administration of small molecules that alter this might be a novel approach for treatment of wound-healing disorders. Itaconate is a tricarboxylic acid (TCA) cycle-derived metabolite that has been associated with resolution of macrophage-mediated inflammation. However, its effects on macrophage wound healing functions are unknown. In this study, we investigated the effects of the membrane-permeable 4-octyl itaconate (4-OI) derivative on ECM scavenging by cultured human blood monocyte-derived macrophages (hMDM). We found that 4-OI reduced signalling of p38 mitogen-activated protein kinase (MAPK) induced by the canonical immune stimulus lipopolysaccharide (LPS). Likely as a consequence of this, the production of the inflammatory mediators like tumor necrosis factor (TNF)-α and cyclooxygenase (COX)-2 were also reduced. On the transcriptional level, 4-OI increased expression of the gene coding for TGF-β (TGFB1), whereas expression of the collagenase matrix metalloprotease-8 (MMP8) was reduced. Furthermore, surface levels of the anti-inflammatory marker CD36, but not CD206 and CD11c, were increased in these cells. To directly investigate the effect of 4-OI on scavenging of ECM by macrophages, we developed an assay to measure uptake of fibrous collagen. We observed that LPS promoted collagen uptake and that this was reversed by 4-OI-induced signaling of nuclear factor erythroid 2–related factor 2 (NRF2), a regulator of cellular resistance to oxidative stress and the reduced glycolytic capacity of the macrophage. These results indicate that 4-OI lowers macrophage inflammation, likely promoting a more wound-resolving phenotype.

Minimal-invasive Vorfußchirurgie: Konzept und Techniken

Minimally invasive surgery (MIS) has advanced to an established approach in the correction of all deformities of the forefoot. For the first ray the minimally invasive chevron and Akin osteotomy (MICA) shows very good clinical results and provides a broad spectrum of indications in comparison to the classical chevron osteotomy. The minimally invasive treatment of hallux rigidus also seems to achieve comparable results to the open techniques, although the surgical indications must be thoroughly evaluated. Lesser toe deformities are often easier to treat with minimally invasive osteotomy, capsule release and tendon lengthening than with complex open procedures and usually do not require any internal fixation material. Compared to the classical Weil osteotomy, distal metatarsal osteotomy shows areduced rate of cock-up deformities and does not require internal fixation. In relation to open procedures, minimally invasive approaches should be accepted as avaluable addition and alternative to the classical open techniques due to the reduced rate of wound healing disorders and postoperative pain.

Postoperative complications and oncologic outcomes after multimodal therapy of localized high risk soft tissue sarcoma

BackgroundStandard therapy for localized high-risk soft tissue sarcoma includes surgical resection and neoadjuvant or adjuvant radiation therapy (± chemotherapy and locoregional hyperthermia). No difference in oncologic outcomes for patients treated with neoadjuvant and adjuvant radiation therapy was reported, whereas side effect profiles differ. The aim of this analysis was to analyse oncologic outcomes and postoperative complications in patients treated with multimodal treatment.MethodsOncologic outcomes and major wound complications (MWC, subclassified as wound healing disorder, infection, abscess, fistula, seroma and hematoma) were evaluated in 74 patients with localized high-risk soft tissue sarcoma of extremities and trunk undergoing multimodal treatment, and also separately for the subgroup of lower extremity tumors. Clinical factors and treatment modalities (especially neoadjuvant vs. adjuvant radiotherapy) were evaluated regarding their prognostic value and impact on postoperative wound complications.ResultsOncologic outcomes were dependent on number of high risk features (tumor size, depth to superficial fascia and grading), but not on therapy sequencing (however with higher risk patients in the neoadjuvant group). Different risk factors influenced different subclasses of wound healing complications. Slightly higher MWC-rates were observed in patients treated with neoadjuvant therapy, compared to adjuvant radiotherapy, although only with a trend to statistical significance (31.8% vs. 13.3%, p = 0.059). However, except for wound infections, no significant difference for other subclasses of postoperative complications was observed between neoadjuvant and adjuvant therapy. Diabetes was confirmed as a major risk factor for immune-related wound complications.ConclusionRates of major wound complications in this cohort are comparable to published data, higher rates of wound infections were observed after neoadjuvant radiotherapy. Tumor localization, patient age and diabetes seem to be major risk factors. The number of risk factors for high risk soft tissue sarcoma seem to influence DMFS. Neoadjuvant treatment increases the risk only for wound infection treated with oral or intravenous antibiotic therapy and appears to be a safe option at an experienced tertiary center in absence of other risk factors.

Bariatric surgery in liver cirrhosis.

Obesity is frequently associated with its hepatic manifestation, the nonalcoholic fatty liver disease (NAFLD). The most effective treatment for morbid obesity is bariatric surgery (BS) also improving NAFLD and liver function. In patients where NAFLD has already progressed to liver cirrhosis, BS can be considered a high-risk procedure. Hence, consideration of the procedure and the most appropriate timing is crucial. Obese patients suffering from NAFLD who underwent BS from two German University Medical Centers were retrospectively analyzed. Twenty-seven patients underwent BS. Most common procedures were laparoscopic Roux-en-Y-gastric (RYGB) and laparoscopic sleeve gastrectomy (SG). All patients suffered from liver cirrhosis Child A. A preoperative transjugular portosystemic shunt (TIPS) was established in three patients and failed in another patient. Postoperative complications consisted of wound healing disorders (n = 2), anastomotic bleeding (n = 1), and leak from the staple line (n = 1). This patient suffered from intraoperatively detected macroscopic liver cirrhosis. Excess weight loss was 73% and 85% after 1 and 2 years, respectively. Two patients suffered from postoperative aggravation of their liver function, resulting in a higher Child-Pugh score, while three could be removed from the waiting list for a liver transplantation. BS leads to weight loss, both after SG and RYGB, and potential improvement of liver function in liver cirrhosis. These patients need to be considered with care when evaluated for BS. Preoperative TIPS implantation may reduce the perioperative risk in selected patients.

Engineering Human Mesenchymal Bodies in a Novel 3D-Printed Microchannel Bioreactor for Extracellular Vesicle Biogenesis.

Human Mesenchymal Stem Cells (hMSCs) and their derived products hold potential in tissue engineering and as therapeutics in a wide range of diseases. hMSCs possess the ability to aggregate into "spheroids", which has been used as a preconditioning technique to enhance their therapeutic potential by upregulating stemness, immunomodulatory capacity, and anti-inflammatory and pro-angiogenic secretome. Few studies have investigated the impact on hMSC aggregate properties stemming from dynamic and static aggregation techniques. hMSCs' main mechanistic mode of action occur through their secretome, including extracellular vesicles (EVs)/exosomes, which contain therapeutically relevant proteins and nucleic acids. In this study, a 3D printed microchannel bioreactor was developed to dynamically form hMSC spheroids and promote hMSC condensation. In particular, the manner in which dynamic microenvironment conditions alter hMSC properties and EV biogenesis in relation to static cultures was assessed. Dynamic aggregation was found to promote autophagy activity, alter metabolism toward glycolysis, and promote exosome/EV production. This study advances our knowledge on a commonly used preconditioning technique that could be beneficial in wound healing, tissue regeneration, and autoimmune disorders.

Safety and efficacy of direct cardiac shockwave therapy in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (the CAST-HF trial): study protocol for a randomized controlled trial—an update

Coronary artery disease (CAD) remains a severe socio-economic burden in the Western world. Coronary obstruction and subsequent myocardial ischemia result in the progressive replacement of contractile myocardium with dysfunctional, fibrotic scar tissue. Post-infarctional remodelling is causal for the concomitant decline of left-ventricular function and the fatal syndrome of heart failure. Available neurohumoral treatment strategies aim at the improvement of symptoms. Despite extensive research, therapeutic options for myocardial regeneration, including (stem)-cell therapy, gene therapy, cellular reprogramming or tissue engineering, remain purely experimental. Thus, there is an urgent clinical need for novel treatment options for inducing myocardial regeneration and improving left-ventricular function in ischemic cardiomyopathy. Shockwave therapy (SWT) is a well-established regenerative tool that is effective for the treatment of chronic tendonitis, long-bone non-union and wound-healing disorders. In preclinical trials, SWT regenerated ischemic myocardium via the induction of angiogenesis and the reduction of fibrotic scar tissue, resulting in improved left-ventricular function. In this prospective, randomized controlled, single-blind, monocentric study, 80 patients with reduced left-ventricular ejection fraction (LVEF≤ 40%) are subjected to coronary-artery bypass-graft surgery (CABG) surgery and randomized in a 1:1 ratio to receive additional cardiac SWT (intervention group; 40 patients) or CABG surgery with sham treatment (control group; 40 patients). This study aims to evaluate (1) the safety and (2) the efficacy of cardiac SWT as adjunctive treatment during CABG surgery for the regeneration of ischemic myocardium. The primary endpoints of the study represent (1) major cardiac events and (2) changes in left-ventricular function 12 months after treatment. Secondary endpoints include 6-min walk test distance, improvement of symptoms and assessment of quality of life. This study aims to investigate the safety and efficacy of cardiac SWT during CABG surgery for myocardial regeneration. The induction of angiogenesis, decrease of fibrotic scar tissue formation and, thus, improvement of left-ventricular function could lead to improved quality of life and prognosis for patients with ischemic heart failure. Thus, it could become the first clinically available treatment strategy for the regeneration of ischemic myocardium alleviating the socio-economic burden of heart failure. ClinicalTrials.gov NCT03859466. Registered on 1 March 2019.