Transabdominalepelviceperineal (TAPP) anterolateral thigh flap: A new reconstructive technique for complex defects following extended abdominoperineal resection

Background: Abdominoperineal resection (APR) following radiotherapy is associated with a high rate of perineal wound complications. The anterolateral thigh (ALT) flap, combined with the vastus lateralis (VL) muscle, can cover complex perineal and pelvic anteroposterior defects. This is used for the first time transabdominally through the pelvis and the perineum (TAPP) in the infero-posterior directions; this technique has been described and illustrated in this study. Methods: Among over 90 patients who underwent perineal reconstruction between May 2004 and June 2011, six patients presented high-grade tumours invading perineum, pelvis and sacrum, thereby resulting in a continuous anteroposterior defect. ALT þ VL TAPP reconstructions were performed after extended APR and, subsequently, sacrectomy. Patients were examined retrospectively to determine demographics, operative time, complications (general and flap-related), time to complete healing and length of hospital stay. Long-term flap coverage, flap volume stability and functional and aesthetic outcomes were assessed. Results: Mean operating time of the reconstruction was 290 min. No deaths occurred. One patient presented partial flap necrosis. Another patient presented a novel wound dehiscence after flap healing, due to secondary skin dissemination of the primary tumour. Following volumetric flap analysis on serial post-operative CT scans, no significant flap atrophy was observed. All flaps fully covered the defects. No late complications such as fistulas or perineal hernias occurred. Donor-site recovery was uneventful with no functional deficits. Conclusions: The use of the ALT þ VL flap transabdominally is an innovative method to reconstruct exceptionally complex perineal and pelvic defects extending up to the lower back. This flap guarantees superior bulk, obliterating all pelvic dead space, with the fascia lata (FL) supporting the pelvic floor

Human platelet lysate stimulates neurotrophic properties of human adipose-derived stem cells better than Schwann cell-like cells

Background: Trauma-associated peripheral nerve injury is a widespread clinical problem causing sensory and motor disabilities. Schwann cells (SCs) contribute to nerve regeneration, mainly by secreting nerve growth factor (NGF) and brain-derived neurotrophic factor. In the last years, adipose-derived stem cells (ASCs) differentiated into SCs (SC-ASCs) were considered as promising cell therapy. However, the cell trans-differentiation process has not been effectively showed and presents several drawbacks, thus an alternative approach for increasing ASCs neurotrophic properties is highly demanded. In the context of human cell-based therapies, Good Manufacturing Practice directions indicate that FBS should be substituted with a xenogeneic-free supplement, such as Human Platelet Lysate (HPL). Previously, we demonstrated that neurotrophic properties of HPL-cultured ASCs were superior compared to undifferentiated FBS-cultured ASCs. Therefore, as following step, here we compared the neurotrophic properties of differentiated SC-like ASCs and HPL-cultured ASCs.Methods: Both cell groups were investigated for gene expression level of neurotrophic factors, their receptors and neuronal markers. Moreover, the expression of nestin was quantitatively evaluated by flow cytometry. The commitment toward the SC phenotype was assessed with immunofluorescence pictures. Proteomics analysis was performed on both cells and their conditioned media to compare the differential protein profile. Finally, neurotrophic abilities of both groups were evaluated with a functional co-culture assay, assessing dorsal root ganglia survival and neurite outgrowth.Results: HPL-cultured ASCs demonstrated higher gene expression of NGF and lower expression of S100B. Moreover, nestin was present in almost all HPL-cultured ASCs and only in one quarter of SC-ASCs. Immunofluorescence confirmed that S100B was not present in HPL-cultured ASCs. Proteomics analysis validated the higher expression of nestin and the increase in cytoskeletal and ECM proteins involved in neural regeneration processes. The co-culture assay highlighted that neurite outgrowth was higher in the presence of HPL-ASCs or their conditioned medium compared to SC-ASCs.Conclusions: All together, our results show that HPL-ASCs were more neurotrophic than SC-ASCs. We highlighted that the HPL triggers an immature neuro-induction state of ASCs, while keeping their stem properties, paving the way for innovative therapies for nerve regeneration. Graphical Abstrac

Pedicled Anterolateral Thigh Flap for Abdominal Wall Reconstruction

Large full thickness abdominal wall defects following malignancies can be a reconstructive challenge. The purpose of this study was to analyze long-term outcomes and complications following abdominal wall reconstruction using composite antero-lateral thigh (ALT) flaps.\nThe study retrospectively investigated 16 consecutive patients who underwent abdominal wall reconstruction with autologous flap between May 2003 and March 2018. Volumetric flap analysis was used to assess flap atrophy over time, evaluating the role of denervation and reinnervation. The long-term outcome was assessed to compare the two groups (free vs. pedicled ALT flap reconstructions).\nAll flaps successfully covered the defects. We found a significant increase in flap resorption in free flaps when compared to pedicled ones. Abdominal bulging was seen in 3 out of 16 (19%) patients after more than 12 months follow-up, in close correlation with mesh absence.\nFree flaps were shown to be equally effective as their pedicled counterparts, without significant increase in complication rate.\nBACKGROUND/AIM\nPATIENTS AND METHODS\nRESULTS\nCONCLUSIO

Nirmatrelvir treatment of SARS-CoV-2-infected mice blunts antiviral adaptive immune responses

Alongside vaccines, antiviral drugs are becoming an integral part of our response to the SARS-CoV-2 pandemic. Nirmatrelvir-an orally available inhibitor of the 3-chymotrypsin-like cysteine protease-has been shown to reduce the risk of progression to severe COVID-19. However, the impact of nirmatrelvir treatment on the development of SARS-CoV-2-specific adaptive immune responses is unknown. Here, by using mouse models of SARS-CoV-2 infection, we show that nirmatrelvir administration blunts the development of SARS-CoV-2-specific antibody and T cell responses. Accordingly, upon secondary challenge, nirmatrelvir-treated mice recruited significantly fewer memory T and B cells to the infected lungs and mediastinal lymph nodes, respectively. Together, the data highlight a potential negative impact of nirmatrelvir treatment with important implications for clinical management and might help explain the virological and/or symptomatic relapse after treatment completion reported in some individuals

Adipose-derived stem cells enhance peripheral nerve regeneration.

Traumatic injuries resulting in peripheral nerve lesions often require a graft to bridge the gap. Although autologous nerve auto-graft is still the first-choice strategy in reconstructions, it has the severe disadvantage of the sacrifice of a functional nerve. Cell transplantation in a bioartificial conduit is an alternative strategy to create a favourable environment for nerve regeneration. We decided to test new fibrin nerve conduits seeded with various cell types (primary Schwann cells and adult stem cells differentiated to a Schwann cell-like phenotype) for repair of sciatic nerve injury. Two weeks after implantation, the conduits were removed and examined by immunohistochemistry for axonal regeneration (evaluated by PGP 9.5 expression) and Schwann cell presence (detected by S100 expression). The results show a significant increase in axonal regeneration in the group of fibrin seeded with Schwann cells compared with the empty fibrin conduit. Differentiated adipose-derived stem cells also enhanced regeneration distance in a similar manner to differentiated bone marrow mesenchymal stem cells. These observations suggest that adipose-derived stem cells may provide an effective cell population, without the limitations of the donor-site morbidity associated with isolation of Schwann cells, and could be a clinically translatable route towards new methods to enhance peripheral nerve repair

Adipose-derived stem cells enhance peripheral nerve regeneration.

Traumatic injuries resulting in peripheral nerve lesions often require a graft to bridge the gap. Although autologous nerve auto-graft is still the first-choice strategy in reconstructions, it has the severe disadvantage of the sacrifice of a functional nerve. Cell transplantation in a bioartificial conduit is an alternative strategy to create a favourable environment for nerve regeneration. We decided to test new fibrin nerve conduits seeded with various cell types (primary Schwann cells and adult stem cells differentiated to a Schwann cell-like phenotype) for repair of sciatic nerve injury. Two weeks after implantation, the conduits were removed and examined by immunohistochemistry for axonal regeneration (evaluated by PGP 9.5 expression) and Schwann cell presence (detected by S100 expression). The results show a significant increase in axonal regeneration in the group of fibrin seeded with Schwann cells compared with the empty fibrin conduit. Differentiated adipose-derived stem cells also enhanced regeneration distance in a similar manner to differentiated bone marrow mesenchymal stem cells. These observations suggest that adipose-derived stem cells may provide an effective cell population, without the limitations of the donor-site morbidity associated with isolation of Schwann cells, and could be a clinically translatable route towards new methods to enhance peripheral nerve repair

The “Sombrero-Shape” Super-Thin Pedicled ALT Flap for Complete Scrotal Reconstruction Following Fournier's Gangrene

When the scrotal sac is entirely debrided following a Fournier gangrene, testes exposure poses unique challenges for the reconstructive surgeon. Despite the anterolateral thigh (ALT) flap is considered a workhorse in such context, aesthetic results are often suboptimal because of the lack of natural ptosis and patchwork appearance. We describe the use of a super-thin pedicled ALT flap for total scrotal reconstruction, modified according to a peculiar flap design and inset technique. A 42-year-old man was referred to our department for delayed total scrotal reconstruction 8 months after a Fournier gangrene extensive debridement. A super-thin pedicled ALT flap from the right thigh was designed: in the central portion of the ALT, a lateral skin paddle extension was marked to guarantee adequate posterior anchorage during insetting and ptosis of the scrotal sac. This particular flap arrangement has inspired the name "sombrero" as the shape is akin to the famous hat. No secondary refinements were needed, and the patient showed satisfying aesthetic and functional results at 12 months' follow-up. The ALT flap design "sombrero" modification proposed in this article can improve scrotum cosmesis and patient satisfaction in a single-stage single-flap procedure

Breast Reconstruction: Economic Impact Swiss Health Insurance System

Background: Considering present concerns about healthcare costs and the lack of evidence and published articles on breast reconstruction costs in Switzerland, we retrospectively investigated charges to the Swiss healthcare system for different breast reconstruction procedures at the Centre Hospitalier Universitaire Vaudois. Methods: We selected all hospitalized patients at the University Hospital who underwent a “total” delayed breast reconstruction from January 2012 to December 2015. Analysis included 72 women who underwent autologous or implant-based reconstructions. Three main breast reconstruction techniques were included: Deep Inferior Epigastric Perforator (n = 46) autologous flap reconstruction, Tissue Expander followed by Implant (n = 12) and pedicled Latissimus Dorsi (n = 12) flap with or without tissue expander and implant (n = 7). For all different groups, the global costs of reconstruction and total number of required operations were statistically compared. Results: Global costs for Deep Inferior Epigastric Perforator reconstruction were 29,728 ± 1892 CHF (avg ± Std. Error of Mean), while Tissue Expander reconstruction showed a significantly higher global cost, reaching an average of 44,313 ± 5553 CHF (avg ± Std. Error of Mean). LD showed a similar cost, compared to the Deep Inferior Epigastric Perforator reconstruction (29,813 ± 3637 CHF), increasing when including an implant (37,688 ± 4840 CHF). No significant differences in the number of interventions were detected. Conclusion: These data show that autologous breast reconstruction (DIEP) delivers the best cost ratio, with lower overall costs. Implant-based reconstructions showed a greater likelihood of complications and re-intervention, globally creating superior costs when compared to autologous reconstructions

FastSkin® Concept : A Novel Treatment for Complex Acute and Chronic Wound Management

Successful treatments for acute and chronic skin wounds remain challenging. The goal of this proof-of-concept study was to assess the technical feasibility and safety of a novel wound treatment solution, FastSkin®, in a pig model. FastSkin® was prepared from skin micrografts patterned in blood using acoustic waves. Upon coagulation, the graft was transferred on a silicone sheet and placed on wounds. Six full-thickness wounds were created at the back of two pigs and treated with either FastSkin®, split-thickness skin graft (positive control), a gauze coverage (negative control, NC1), or blood patterned without micrografts (negative control, NC2). Silicone sheets were removed after 7, 14, and 21 days. Wound healing was monitored for six weeks and evaluated macroscopically for re-epithelialization and morphometrically for residual wound area and wound contraction. Tissue regeneration was assessed with histology after six weeks. Re-epithelialization was faster in wounds covered with FastSkin® treatments compared to NC2 and in NC2 compared to NC1. Importantly, an enhanced collagen organization was observed in FastSkin® in contrast to NC treatments. In summary, two clinically approved skin wound treatments, namely micrografting and blood clot graft, were successfully merged with sound-induced patterning of micrografts to produce an autologous, simple, and biologically active wound treatment concept.</p