Negative Pressure Wound Therapy in Free Muscle Flaps-Risk or Benefit?

BACKGROUND: Application of negative pressure wound therapy (NPWT) on free flaps not only reduces edema but also increases the pressure from outside. The impact of these opposite effects on flap perfusion remains elusive. This study evaluates the NPWT system's influence on macro- and microcirculation of free flaps and edema reduction to better assess the clinical value of this therapy in microsurgical reconstructions. METHODS: In this open-label, prospective cohort study, a total of 26 patients with free gracilis muscle flaps for distal lower extremity reconstruction were included. Flaps were covered with an NPWT (13 patients) or a conventional, fatty gauze dressing (13 patients) for 5 postoperative days (PODs). Changes in flap perfusion were analyzed by laser Doppler flowmetry, remission spectroscopy, and an implanted Doppler probe. Flap volume as a surrogate parameter for flap edema was evaluated by three-dimensional (3D) scans. RESULTS: No flap showed clinical evidence of circulatory disturbances. The groups showed significant differences in the dynamic of macrocirculatory blood flow velocity with an increase in the NPWT group and a decelerated flow in the control group from PODs 0 to 3 and PODs 3 to 5. No significant differences in microcirculation parameters were observed. 3D scans for estimation of edema development demonstrated significant differences in volume dynamics between the groups. Flap volume of the controls increased, while the volume in the NPWT group decreased during the first 5 PODs. The volume of NPWT-treated flaps decreased even further after NPWT removal from PODs 5 to 14 and significantly more than the flap volume in the control group. CONCLUSION: NPWT is a safe form of dressing for free muscle flaps that enhances blood flow and results in a sustainable edema reduction. The use of NPWT dressings for free flaps should therefore be considered not only as a pure wound covering but also as a supportive therapy for free tissue transfer.

High RIPK3 expression is associated with a higher risk of early kidney transplant failure.

Renal ischemia-reperfusion injury (IRI) is associated with reduced allograft survival, and each additional hour of cold ischemia time increases the risk of graft failure and mortality following renal transplantation. Receptor-interacting protein kinase 3 (RIPK3) is a key effector of necroptosis, a regulated form of cell death. Here, we evaluate the first-in-human RIPK3 expression dataset following IRI in kidney transplantation. The primary analysis included 374 baseline biopsy samples obtained from renal allografts 10 minutes after onset of reperfusion. RIPK3 was primarily detected in proximal tubular cells and distal tubular cells, both of which are affected by IRI. Time-to-event analysis revealed that high RIPK3 expression is associated with a significantly higher risk of one-year transplant failure and prognostic for one-year (death-censored) transplant failure independent of donor and recipient associated risk factors in multivariable analyses. The RIPK3 score also correlated with deceased donation, cold ischemia time and the extent of tubular injury.

Hypoxia Preconditioned Serum (HPS) Promotes Proliferation and Chondrogenic Phenotype of Chondrocytes In Vitro.

Autologous chondrocyte implantation (ACI) for the treatment of articular cartilage defects remains challenging in terms of maintaining chondrogenic phenotype during in vitro chondrocyte expansion. Growth factor supplementation has been found supportive in improving ACI outcomes by promoting chondrocyte redifferentiation. Here, we analysed the chondrogenic growth factor concentrations in the human blood-derived secretome of Hypoxia Preconditioned Serum (HPS) and assessed the effect of HPS-10% and HPS-40% on human articular chondrocytes from osteoarthritic cartilage at different time points compared to normal fresh serum (NS-10% and NS-40%) and FCS-10% culture conditions. In HPS, the concentrations of TGF-beta1, IGF-1, bFGF, PDGF-BB and G-CSF were found to be higher than in NS. Chondrocyte proliferation was promoted with higher doses of HPS (HPS-40% vs. HPS-10%) and longer stimulation (4 vs. 2 days) compared to FCS-10%. On day 4, immunostaining of the HPS-10%-treated chondrocytes showed increased levels of collagen type II compared to the other conditions. The promotion of the chondrogenic phenotype was validated with quantitative real-time PCR for the expression of collagen type II (COL2A1), collagen type I (COL1A1), SOX9 and matrix metalloproteinase 13 (MMP13). We demonstrated the highest differentiation index (COL2A1/COL1A1) in HPS-10%-treated chondrocytes on day 4. In parallel, the expression of differentiation marker SOX9 was elevated on day 4, with HPS-10% higher than NS-10/40% and FCS-10%. The expression of the cartilage remodelling marker MMP13 was comparable across all culture conditions. These findings implicate the potential of HPS-10% to improve conventional FCS-based ACI culture protocols by promoting the proliferation and chondrogenic phenotype of chondrocytes during in vitro expansion.

Aesthetic training concept during plastic surgery residency - Opportunity or risk?

Background: Aesthetic surgery training renders to be challenging to acquire sufficient hands-on experience during residency. To resolve this problem, the "Munich Model" was established in our clinic: Senior residents perform aesthetic surgeries, supervised by an experienced plastic surgeon while patients benefit from reduced surgery costs. With this model, we hypothesize no significant differences in the postoperative outcome between procedures performed by residents and plastic surgeons. Methods: Between August 2012 and December 2017, 481 aesthetic surgeries were included in this retrospective single-center study, of which 283 were performed by residents and 198 by plastic surgeons. Procedures included mastopexy, abdominoplasty, extremity lift, breast reduction, breast augmentation, facial surgery, aesthetic liposuction and lipedema liposuction. Postoperative outcomes were compared regarding surgery time, time of drain removal, inpatient length of stay, duration of wound healing, perioperative blood loss and occurrence of major (surgical revision needed) and minor complications (no surgery needed). Results: We found no significant differences in aesthetic surgical procedures between residents and board-certified plastic surgeons in the outcome measures of surgery duration, time of drain removal, inpatient length of stay, perioperative blood loss and complication rate, including major and minor complications. Only the inpatient stay was prolonged in aesthetic liposuctions performed by residents. Conclusion: This study demonstrates comparatively that supervised aesthetic surgeries at a university hospital utilizing the "Munich Model" widely meet the specialist surgeons' standards.

The Incidence of IgG4-Related and Inflammatory Abdominal Aortic Aneurysm Is Rare in a 101 Patient Cohort.

Abdominal aortic aneurysms (AAA) are the most frequent aortic dilation, with considerable morbidity and mortality. Inflammatory (infl) and IgG4-positive AAAs represent specific subtypes of unclear incidence and clinical significance. Here, histologic and serologic analyses with retrospective clinical data acquisition are investigated via detailed histology, including morphologic (HE, EvG: inflammatory subtype, angiogenesis, and fibrosis) and immunhistochemic analyses (IgG and IgG4). In addition, complement factors C3/C4 and immunoglobulins IgG, IgG2, IgG4 and IgE were measured in serum samples and clinical data uses patients' metrics, as well as through semi-automated morphometric analysis (diameter, volume, angulation and vessel tortuosity). A total of 101 eligible patients showed five (5%) IgG4 positive (all scored 1) and seven (7%) inflammatory AAAs. An increased degree of inflammation was seen in IgG4 positive and inflAAA, respectively. However, serologic analysis revealed no increased levels of IgG or IgG4. The operative procedure time was not different for those cases and the short-term clinical outcomes were equal for the entire AAA cohort. Overall, the incidence of inflammatory and IgG4-positive AAA samples seems very low based on histologic and serum analyses. Both entities must be considered distinct disease phenotypes. Short-term operative outcomes were not different for both sub-cohorts.

CNS demyelinating events in primary Sjögren's syndrome: A single-center case series on the clinical phenotype.

Objective: The study aimed to assess the prevalence, clinical characteristics, and therapeutic outcomes of the central nervous system (CNS) demyelinating disease in a large cohort of primary Sjögren's syndrome (pSS). Methods: This is an explorative cross-sectional study of patients with pSS seen in the departments of rheumatology, otorhinolaryngology, or neurology of a tertiary university center between January 2015 and September 2021. Results: In a cohort of 194 pSS patients, 22 patients had a CNS manifestation. In this CNS group, 19 patients had a lesion pattern suggestive of demyelination. While there were no obvious differences in the patients' epidemiological disposition or rate of other extraglandular manifestations, the CNS group differed from the remaining patients with pSS by having less glandular manifestations but a higher seroprevalence for anti-SSA/Ro antibodies. Notably, patients with CNS manifestations were often diagnosed with multiple sclerosis (MS) and treated as such, although age and disease course were atypical of MS. Many first-line MS agents were ineffective in these "MS look-alikes"; however, the disease course was benign with B-cell-depleting agents. Conclusion: Neurological symptoms of pSS are common and clinically manifest mainly as myelitis or optic neuritis. Notably, in the CNS, the pSS phenotype can overlap with MS. The prevailing disease is crucial since it has a major impact on the long-term clinical outcome and the choice of disease-modifying agents. Although our observations neither confirm pSS as a more appropriate diagnosis nor rule out simple comorbidity, physicians should consider pSS in the extended diagnostic workup of CNS autoimmune diseases.

Comparison of the Effect of Different Conditioning Media on the Angiogenic Potential of Hypoxia Preconditioned Blood-Derived Secretomes: Towards Engineering Next-Generation Autologous Growth Factor Cocktails.

Hypoxia Preconditioned Plasma (HPP) and Serum (HPS) are regenerative blood-derived growth factor compositions that have been extensively examined for their angiogenic and lymphangiogenic activity towards wound healing and tissue repair. Optimization of these secretomes' growth factor profile, through adjustments of the conditioning parameters, is a key step towards clinical application. In this study, the autologous liquid components (plasma/serum) of HPP and HPS were replaced with various conditioning media (NaCl, PBS, Glucose 5%, AIM V medium) and were analyzed in terms of key pro- (VEGF-A, EGF) and anti-angiogenic (TSP-1, PF-4) protein factors, as well as their ability to promote microvessel formation in vitro. We found that media substitution resulted in changes in the concentration of the aforementioned growth factors, and also influenced their ability to induce angiogenesis. While NaCl and PBS led to a lower concentration of all growth factors examined, and consequently an inferior tube formation response, replacement with Glucose 5% resulted in increased growth factor concentrations in anticoagulated blood-derived secretomes, likely due to stimulation of platelet factor release. Medium substitution with Glucose 5% and specialized peripheral blood cell-culture AIM V medium generated comparable tube formation to HPP and HPS controls. Altogether, our data suggest that medium replacement of plasma and serum may significantly influence the growth factor profile of hypoxia-preconditioned blood-derived secretomes and, therefore, their potential application as tools for promoting therapeutic angiogenesis.

In Vitro Comparison of Lymphangiogenic Potential of Hypoxia Preconditioned Serum (HPS) and Platelet-Rich Plasma (PRP).

Strategies for therapeutic lymphangiogenesis are gradually directed toward the use of growth factor preparations. In particular, blood-derived growth factor products, including Hypoxia Preconditioned Serum (HPS) and Platelet-rich Plasma (PRP), are both clinically employed for accelerating tissue repair and have received considerable attention in the field of regenerative medicine research. In this study, a comparative analysis of HPS and PRP was conducted to explore their lymphangiogenic potential. We found higher pro-lymphangiogenic growth factor concentrations of VEGF-C, PDGF-BB, and bFGF in HPS in comparison to normal serum (NS) and PRP. The proliferation and migration of lymphatic endothelial cells (LECs) were promoted considerably with both HPS and PRP, but the strongest effect was achieved with HPS-40% dilution. Tube formation of LECs showed the highest number of tubes, branching points, greater tube length, and cell-covered area with HPS-10%. Finally, the effects were double-validated using an ex vivo lymphatic ring assay, in which the highest number of sprouts and the greatest sprout length were achieved with HPS-10%. Our findings demonstrate the superior lymphangiogenic potential of a new generation blood-derived secretome obtained by hypoxic preconditioning of peripheral blood cells-a method that offers a novel alternative to PRP.

The Rise of Facial Palsy on Social Media Over the Last 5 Years.

BACKGROUND: Social media (SoMe) has become a powerful platform for distributing health information. Facial palsy (FP) results in functional and social impairment and lowers quality of life. Social media may help to raise awareness of FP sequalae. This study aims to determine the FP information growth on SoMe platforms and parameters that influence user engagement on FP content. METHODS: Five commonly used SoMe platforms (Facebook, Instagram, TikTok, Twitter, and Reddit) were analyzed. Data on 18 FP hashtags and their social interaction parameters (posts, likes, reaches, comments, shares, language, and country of origin) over the past 5 years (July 31, 2016, to July 31, 2021) were collected. In-depth account analysis was performed on the 5 most popular Instagram profiles associated with FP. RESULTS: The annual growth curve was positive on each platform. Facial Palsy Awareness Week 2021 trended best on TikTok. Facebook accumulated 315,411 likes and 1,922,678 reaches on 8356 posts. On Instagram, 24,968 posts gathered 4,904,124 likes and 9,215,852 reaches. TikTok users interacted on 3565 posts, accumulating 4,304,155 likes and 4,200,368 reaches. The implementation of reels ( P <0.001) and the profile host interacting with their followers by liking ( P <0.001) and replying ( P <0.001) to users' comments significantly increased the engagement rate. CONCLUSIONS: Facial palsy is of increasing interest on SoMe. Facial palsy surgeons may post reels, interact with their community, and engage into FPAW to promote user engagement.

Thinking like a Lawyer-Human Rights and Their Association with the Plastic Surgeon of Today.

Plastic surgeons are trained to perform a wide repertoire of surgeries-ranging from standard local procedures to highly specialized operations. Therefore, plastic surgeons treat a plethora of clinical presentations and address multiple patient needs. Their daily workflow is increasingly entwined with legal topics. The concrete legal interpretation falls within the remit of legal experts. However, by understanding the legal basics of selected surgical procedures, plastic surgeons may generate synergies in patient care and clinical practice. The legal situation is to be elucidated based on the German Basic Law (GBL) and the European Convention on Human Rights (ECHR). LEVEL OF EVIDENCE V: "This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 ."

Relevance of the Scaphoid Shift Test for the Investigation of Scapholunate Ligament Injuries.

Background: Although it is part of the common clinical examination of scapholunate ligament pathologies, there are only little data on the diagnostic value of the scaphoid shift test. The aim of this study was to evaluate the scaphoid shift test in a large cohort of patients. Materials and Methods: We retrospectively analysed 447 patients who underwent the scaphoid shift test and wrist arthroscopy because of various suspected injuries of the wrist, correlating the results of clinical examination with data obtained during the wrist arthroscopy. Sensitivity, specificity, and positive and negative predictive values were calculated and evaluated. Results: The sensitivity of the scaphoid shift test was low (0.50) when examining the whole cohort. In a subgroup of patients specifically referred for suspected scapholunate ligament injury, the sensitivity was higher (0.61), but the specificity was low (0.62). In detecting more serious lesions (Geissler 3 + 4), the scaphoid shift test demonstrated higher sensitivity (0.66). Conclusions: An isolated scaphoid shift test may only be of limited value in the diagnosis of scapholunate ligament lesions and should, therefore, be viewed as a useful tool for a preliminary assessment, but a negative test should not prevent the surgeon from indicating a more extensive diagnostic workup.

Hypoxia Preconditioned Serum (HPS) Promotes Osteoblast Proliferation, Migration and Matrix Deposition.

Interest in discovering new methods of employing natural growth factor preparations to promote bone fracture healing is becoming increasingly popular in the field of regenerative medicine. In this study, we were able to demonstrate the osteogenic potential of hypoxia preconditioned serum (HPS) on human osteoblasts in vitro. Human osteoblasts were stimulated with two HPS concentrations (10% and 40%) and subsequently analyzed at time points of days 2 and 4. In comparison to controls, a time- and dose-dependent (up to 14.2× higher) proliferation of osteoblasts was observed after 4 days of HPS-40% stimulation with lower lactate dehydrogenase (LDH)-levels detected than controls, indicating the absence of cytotoxic/stress effects of HPS on human osteoblasts. With regards to cell migration, it was found to be significantly faster with HPS-10% application after 72 h in comparison to controls. Further osteogenic response to HPS treatment was evaluated by employing culture supernatant analysis, which exhibited significant upregulation of OPG (Osteoprotegerin) with higher dosage (HPS-10% vs. HPS-40%) and longer duration (2 d vs. 4 d) of HPS stimulation. There was no detection of anti-osteogenic sRANKL (soluble Receptor Activator of NF-κB Ligand) after 4 days of HPS stimulation. In addition, ALP (alkaline phosphatase)-enzyme activity, was found to be upregulated, dose-dependently, after 4 days of HPS-40% application. When assessing ossification through Alizarin-Red staining, HPS dose-dependently achieved greater (up to 2.8× higher) extracellular deposition of calcium-phosphate with HPS-40% in comparison to controls. These findings indicate that HPS holds the potential to accelerate bone regeneration by osteogenic promotion of human osteoblasts.

Hypoxia Preconditioned Serum (HPS)-Hydrogel Can Accelerate Dermal Wound Healing in Mice-An In Vivo Pilot Study.

The ability to use the body's resources to promote wound repair is increasingly becoming an interesting area of regenerative medicine research. Here, we tested the effect of topical application of blood-derived hypoxia preconditioned serum (HPS) on wound healing in a murine wound model. Alginate hydrogels loaded with two different HPS concentrations (10 and 40%) were applied topically on full-thickness wounds created on the back of immunocompromised mice. We achieved a significant dose-dependent wound area reduction after 5 days in HPS-treated groups compared with no treatment (NT). On average, both HPS-10% and HPS-40% -treated wounds healed 1.4 days faster than NT. Healed tissue samples were investigated on post-operative day 15 (POD 15) by immunohistology and showed an increase in lymphatic vessels (LYVE-1) up to 45% with HPS-40% application, while at this stage, vascularization (CD31) was comparable in the HPS-treated and NT groups. Furthermore, the expression of proliferation marker Ki67 was greater on POD 15 in the NT-group compared to HPS-treated groups, in accordance with the earlier completion of wound healing observed in the latter. Collagen deposition was similar in all groups, indicating lack of scar tissue hypertrophy as a result of HPS-hydrogel treatment. These findings show that topical HPS application is safe and can accelerate dermal wound healing in mice.

Comprehensive characterization of central BCL-2 family members in aberrant eosinophils and their impact on therapeutic strategies.

PURPOSE: Hypereosinophilia represents a heterogenous group of severe medical conditions characterized by elevated numbers of eosinophil granulocytes in peripheral blood, bone marrow or tissue. Treatment options for hypereosinophilia remain limited despite recent approaches including IL-5-targeted monoclonal antibodies and tyrosine kinase inhibitors. METHODS: To understand aberrant survival patterns and options for pharmacologic intervention, we characterized BCL-2-regulated apoptosis signaling by testing for BCL-2 family expression levels as well as pharmacologic inhibition using primary patient samples from diverse subtypes of hypereosinophilia (hypereosinophilic syndrome n = 18, chronic eosinophilic leukemia not otherwise specified n = 9, lymphocyte-variant hypereosinophilia n = 2, myeloproliferative neoplasm with eosinophilia n = 2, eosinophilic granulomatosis with polyangiitis n = 11, reactive eosinophilia n = 3). RESULTS: Contrary to published literature, we found no difference in the levels of the lncRNA Morrbid and its target BIM. Yet, we identified a near complete loss of expression of pro-apoptotic PUMA as well as a reduction in anti-apoptotic BCL-2. Accordingly, BCL-2 inhibition using venetoclax failed to achieve cell death induction in eosinophil granulocytes and bone marrow mononuclear cells from patients with hypereosinophilia. In contrast, MCL1 inhibition using S63845 specifically decreased the viability of bone marrow progenitor cells in patients with hypereosinophilia. In patients diagnosed with Chronic Eosinophilic Leukemia (CEL-NOS) or Myeloid and Lymphatic Neoplasia with hypereosinophilia (MLN-Eo) repression of survival was specifically powerful. CONCLUSION: Our study shows that MCL1 inhibition might be a promising therapeutic option for hypereosinophilia patients specifically for CEL-NOS and MLN-Eo.

The Declining Number of Finger Replantations in Germany.

INTRODUCTION: Data from the United States have shown that finger replantation numbers have declined significantly in recent years. It is unclear whether this is due to a decrease in amputation injuries or other reasons. MATERIALS METHODS: Since 2005, all German hospitals have been required to produce structured quality reports. Based on these reports, we analyzed finger and hand replantation development and the incidence of amputation injuries between 2006 and 2018. RESULTS: Replantations decreased by 30%, whereas amputation injuries increased slightly. In 2018, only 17 centers carried out more than 10 replantations. Most hospitals had replanted less than 4 times a year. The majority of residents participated in fewer than 1 replantation per year. Most specialists performed fewer than 1 replantation per year. The reasons for the decline in replantation remain speculative. CONCLUSIONS: However, a reduction in amputation injuries was not observed. A change in medical indications, technical skills, and economic motivations needs to be considered. A further loss of specialized technical skills and experience with replantations might be a future consequence of this trend.

Surgical experience and different glove wearing conditions affect tactile sensibility.

Background: The fingers' tactile sensibility is essential in surgery, especially in microsurgery. Therefore, surgeons seeking to improve their performance often prefer certain glove brands and wearing habits. There is the need of objectively testing these glove wearing conditions and determine the effect of surgical experience with regard to tactile sensibility by comparing surgeons with non-surgeons. Methods: This cross-sectional single-center pilot-study was conducted between June and August 2021. Two groups of 27 surgeons and 27 non-surgeons underwent two-point-discrimination (2PD) and Semmes-Weinstein monofilament testing (SWMT) of both index fingers with bare hands and with wearing six different brands of surgical gloves. Different wearing conditions, such as single-gloving, double-gloving, well-fitted, under- and oversized gloves, were evaluated within and between the groups. Results: Most glove types decreased tactile sensibility (2PD and SWMT) of surgeons and non-surgeons. Interestingly, the thinnest gloves showed similar 2PD values to bare hands in both groups. Double-gloving negatively impacted SWMT, without influencing 2PD. Undersized gloves showed better 2PD and SWMT than well-fitted gloves, while oversized gloves showed no tactile drawbacks. With bare hands and certain glove conditions, the surgeons' 2PD and SWMT was significantly better than the non-surgeons', indicating a positive effect of surgical experience on tactile sensibility. Conclusion: Our study demonstrated the positive impact of surgical experience on tactile sensibility, as demonstrated by the surgeons. The sensibility of the gloved hand varies on the surgical glove type, but favors thinner gloves, single gloving (rather than double gloving) and undersized or well-fitted gloves.

Corrigendum to "Do your surgical glove characteristics and wearing habits affect your tactile sensibility?" [Ann. Med. Surg. Volume 57, September 2020, Pages 281-286].

[This corrects the article DOI: 10.1016/j.amsu.2020.08.002.].