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.

Calponin 1 contributes to myofibroblast differentiation of human pleural mesothelial cells

Pleural mesothelial cells (PMCs) can become myofibroblasts via mesothelial-mesenchymal transition (MesoMT) and contribute to pleural organization, fibrosis, and rind formation. However, how these transformed mesothelial cells contribute to lung fibrosis remains unclear. Here, we investigated the mechanism of contractile myofibroblast differentiation of PMCs. TGF-b induced marked upregulation of calponin 1 expression, which was correlated with notable cytoskeletal rearrangement in human PMCs (HPMCs) to produce stress fibers. Downregulation of calponin 1 expression reduced stress fiber formation. Interestingly, induced stress fibers predominantly contain αSMA associated with calponin 1 but not b-actin. Calponin 1 associated stress fibers also contained myosin II and α-actinin. Further, focal adhesions were aligned with the produced stress fibers. These results suggest that calponin 1 facilitates formation of stress fibers that resemble contractile myofibrils. Supporting this notion, TGF-b significantly increased the contractile activity of HPMCs, an effect that was abolished by downregulation of calponin 1 expression. We infer that differentiation of HPMCs to contractile myofibroblasts facilitates stiffness of scar tissue in pleura to promote pleural fibrosis and that upregulation of calponin 1 plays a central role in this process.

The Polygenic Map of Keloid Fibroblasts Reveals Fibrosis-Associated Gene Alterations in Inflammation and Immune Responses

Due to many inconsistencies in differentially expressed genes (DEGs) related to genomic expression changes during keloid formation and a lack of satisfactory prevention and treatment methods for this disease, the critical biomarkers related to inflammation and the immune response affecting keloid formation should be systematically clarified. Normal skin/keloid scar tissue-derived fibroblast genome expression data sets were obtained from the Gene Expression Omnibus (GEO) and ArrayExpress databases. Hub genes have a high degree of connectivity and gene function aggregation in the integration network. The hub DEGs were screened by gene-related protein–protein interactions (PPIs), and their biological processes and signaling pathways were annotated to identify critical biomarkers. Finally, eighty-one hub DEGs were selected for further analysis, and some noteworthy signaling pathways and genes were found to be closely related to keloid fibrosis. For example, IL17RA is involved in IL-17 signal transduction, TIMP2 and MMP14 activate extracellular matrix metalloproteinases, and TNC, ITGB2, and ITGA4 interact with cell surface integrins. Furthermore, changes in local immune cell activity in keloid tissue were detected by DEG expression, immune cell infiltration, and mass CyTOF analyses. The results showed that CD4+ T cells, CD8+ T cells and NK cells were abnormal in keloid tissue compared with normal skin tissue. These findings not only support the key roles of fibrosis-related pathways, immune cells and critical genes in the pathogenesis of keloids but also expand our understanding of targets that may be useful for the treatment of fibrotic diseases.

Clinical Comparison of Diode Laser Assisted “v-Shape Frenectomy” and Conventional Surgical Method as Treatment of Ankyloglossia

(1) Background: Ankyloglossia, or tongue-tie is a condition, in which the tip of tongue cannot protrude beyond the lower incisor teeth because of short frenulum linguae, often containing scar tissue. Limitations of movement are the most important clinical symptoms of this condition, together with feeding, speech, and mechanical problems. (2) Methods: the present study included two groups of patients (group A and group B) including, respectively, 29 and 32 patients (61 patients total), aged from 8 to 12 and presenting ankyloglossia classified according to the Kotlow’s classification. The patients in group A underwent a common surgical procedure. For the patients of group B, a diode laser device (K2 mobile laser, Dentium, Korea) with a micro-pulsed wavelength of 980 ± 10 nm and power of 1.2 watts was used. The post-surgical discomfort of the patients (recording the pain perceived immediately after the end of the anesthesia and during the following week, using the Numeric Rating Scale (NRS) system) and healing characteristics (recorded using the Early Wound Healing Score or EHS) were evaluated. (3) Results: The results shows that the pain in the patients who underwent laser-assisted frenectomy is significantly reduced (p < 0.001) when compared to those who underwent conventional surgical frenectomy, both immediately after surgery (with a reduction in the average NRS of 80.6%) and after the first week (with a reduction in the average NRS of 86.58%). Additionally, in the same patients, an augmentation in the average value of the EHS of 45% was recorded, highlighting significantly (p < 0.001) better quality in the healing of the wound within the 24 h after surgery. Moreover, other advantages observed in the use of laser assisted-frenectomy are the absence of bleeding and, consequently, a clear operative field; no need to use sutures; no need to take painkillers or antibiotics after surgery; and having a faster recovery and less time needed to perform the operation. (4) Conclusions: within the limits of the present study, it seems possible to assert that the laser frenectomy performed using the v-shape technique presents a series of advantages if compared to the conventional surgical method.

Efficacy of platelet-rich plasma lysate in the treatment of patients with post-traumatic eyelid scarring: an overview of clinical cases

Purpose: to evaluate the effectiveness of platelet-rich plasma lysate (PRP) in the treatment of patients with post-traumatic eyelid scarring by clinical examples. Material and methods. Patients with post-traumatic scarring changes in eyelid tissues causing a damage in the functional and cosmetic state of the auxiliary apparatus of the eye were treated in the Department of Plastic Surgery and Eye Prosthetics at the Helmholtz National Medical Research Center of Eye Diseases. Two of the patients, who had been traumatized shortly before the examination and one patient who had rejected surgery were offered treatment by PRP lysate manufactured at the Sklifosovsky Medical Research Institute of Emergency Medicine. After local infiltration anesthesia, each patient received a single injection of PRP lysate (2 ml) into the scar tissue. The result was evaluated at a follow-up that took place 3 months after the injection. Results. The clinical picture of the three patients showed a pronounced positive dynamic of the functional and cosmetic state of the auxiliary eye apparatus, which made the patients reject subsequent (additional) surgical treatment. Conclusion. An improvement tissue repair and regeneration processes after PRP lysate injection allows us to assess this method as an applicable alternative of reconstructive operations in certain cases.

Scar Sarcoidosis as Presenting Finding in Pembrolizumab Induced Systemic Sarcoidosis in Stage III Melanoma: A Case Report

Immune checkpoint blockade using inhibition of Programmed Cell Death-1 (PD-1) improves both progression-free and overall survival in patients with advanced melanoma, but is associated with a unique set of toxicities termed immune-related Adverse Events (irAEs). We present a case of a man with stage IIIc melanoma who was treated with pembrolizumab (anti PD-1). Two months after initiation of the therapy, the patient developed subcutaneous nodules on his upper lip and right knee, both in a pre-existing scar. Histological examination showed non-necrotising granuloma, most consistent with sarcoidosis. PET-CT showed hypermetabolic mediastinal and hilar adenopathies as well as lung lesions and some cutaneous and subcutaneous metabolic hot spots. Bronchoscopy with biopsy of a lymph node confirmed the diagnosis of sarcoidosis. Pembrolizumab was withheld, whereby a gradual decrease and near spontaneous resolution of all lesions was seen over a period of approximately 6 months. The patient is currently in follow up with no evidence of disease recurrence.Our case shows a unique presentation of sarcoidosis in old scar tissue as presenting symptom of pembrolizumab-related systemic sarcoidosis and demonstrates the importance of histological examination of new lesions occurring during checkpoint inhibitor therapy in order to avoid misdiagnosis of melanoma progression.

Robot-assisted pyeloplasty with buccal mucosa graft for the management of an extended recurrent ureteropelvic junction stricture

A clinical case of robot-assisted pyeloplasty with buccal mucosa graft of an extended recurrent stricture of the left ureteropelvic junction is presented. The patient had previously undergone left-sided laparoscopic antevasal pyeloplasty and retrograde endopyelotomies with ureteral stenting. However, after these interventions, the dilatation of the left pelvicalyceal system persisted, the patient complained of lumbar pain and periodic exacerbations of chronic pyelonephritis. Transperitoneal robotic access isolated the ureteral upper third and the ureteropelvic junction from scar tissue, after dissecting the narrowed ureteral section, its length was about 3.0 cm. In this regard, plastic surgery was performed with a buccal mucosa graft, the ureter was drained with a stent. There were no postoperative complications, and on day 3 the patient was discharged. The stent was removed 4 weeks after. During the control ultrasound examination, the renal pelvicalyceal system was relatively reduced, and the patient did not notice any pain.

Safety and Ease of Sheath Insertion During Endovascular Treatment Via the Common Femoral Artery After Endarterectomy With Autologous Repair: A Retrospective Cohort Study

Background Endovascular treatment (EVT) using the common femoral artery (CFA) for access after endarterectomy (EA) may result in sheath insertion difficulties because of subcutaneous scar tissue, as well as difficulties with hemostasis. We evaluated the safety of CFA access and the ease of sheath insertion over time after EA. Method We included 19 patients (21 limbs, 40 cases) in whom the CFA was used after EA with autologous repair as an access route in EVT for peripheral arterial disease in our institution from January 2013 to December 2020. Nine limbs underwent simple closure repair and 12 underwent autologous patch repair. Difficult sheath insertions were defined as those in which additional devices (stiff guidewire or a smaller diameter sheath for dilation) were used for scheduled sheath insertion. The inability to insert a sheath with the scheduled diameter was defined as a failed sheath insertion. We evaluated the EVT timing after EA for difficult sheath insertions, and whether the CFA was repaired with simple closure or autologous patch repair during EA surgery. Results There were 10 (25%) difficult sheath insertions, with one (2.5%) failure. The rate of difficult sheath insertions peaked from 6 months to 1 year after EA and gradually decreased (47% from 6 months to 3 years, 14% thereafter). There were more statistically significant difficult sheath insertions with simple closure repair (50%) than with autologous patch repair (12%) (P = 0.018). Hemostasis devices were used in 90% of EVT cases. The median maximum sheath diameter was 6 Fr (mean = 5.8 Fr). None of the cases required surgical procedures to achieve hemostasis after EVT. Conclusion EVT may be performed safely using the CFA after EA. The difficulty of sheath insertion may differ depending on the EVT timing after EA; it was more difficult with simple closure than with autologous patch repair, possibly related to scar formation.