Sprayable biomimetic double mask with rapid autophasing and hierarchical programming for scarless wound healing.

Current sprayable hydrogel masks lack the stepwise protection, cleansing, and nourishment of extensive wounds, leading to delayed healing with scarring. Here, we develop a sprayable biomimetic double wound mask (BDM) with rapid autophasing and hierarchical programming for scarless wound healing. The BDMs comprise hydrophobic poly (lactide-co-propylene glycol-co-lactide) dimethacrylate (PLD) as top layer and hydrophilic gelatin methacrylate (GelMA) hydrogel as bottom layer, enabling swift autophasing into bilayered structure. After photocrosslinking, BDMs rapidly solidify with strong interfacial bonding, robust tissue adhesion, and excellent joint adaptiveness. Upon implementation, the bottom GelMA layer could immediately release calcium ion for rapid hemostasis, while the top PLD layer could maintain a moist, breathable, and sterile environment. These traits synergistically suppress the inflammatory tumor necrosis factor-α pathway while coordinating the cyclic guanosine monophosphate/protein kinase G-Wnt/calcium ion signaling pathways to nourish angiogenesis. Collectively, our BDMs with self-regulated construction of bilayered structure could hierarchically program the healing progression with transformative potential for scarless wound healing.

The mark of success: The role of vaccine-induced skin scar formation for BCG and smallpox vaccine-associated clinical benefits.

Skin scar formation following Bacille Calmette-Guérin (BCG) or smallpox (Vaccinia) vaccination is an established marker of successful vaccination and 'vaccine take'. Potent pathogen-specific (tuberculosis; smallpox) and pathogen-agnostic (protection from diseases unrelated to the intentionally targeted pathogen) effects of BCG and smallpox vaccines hold significant translational potential. Yet despite their use for centuries, how scar formation occurs and how local skin-based events relate to systemic effects that allow these two vaccines to deliver powerful health promoting effects has not yet been determined. We review here what is known about the events occurring in the skin and place this knowledge in the context of the overall impact of these two vaccines on human health with a particular focus on maternal-child health.

Subcision with platelet-rich plasma and microneedling versus subcision with saline and micro-needling in posttraumatic scars.

BACKGROUND: In treating post-traumatic scars, this study compared the safety and effectiveness of combined subcision with saline and microneedling versus combined subcision with platelet-rich plasma and microneedling. Combined subcision with saline and microneedling or combined subcision with platelet-rich plasma and microneedling were used to treat 36 consecutive individuals with post-traumatic scarring. The Modified Manchester score was used to assess texture change, pigmentation, and surface distortion changes. Each change was given a score between 1 and 4. A lower score (range: 3-12) indicates a better result. The mean of the three individual scores was determined. For best outcomes, each patient needed four treatment sessions for each scar, with a one-month follow-up period following the final treatment. The three variables in group B had mean scores of 1.4 ± 0.5, 2 ± 0.8, and 2.2 ± 0.9, respectively, for texture change, pigmentation, and surface distortion. With a mean score of 1.4 ± 0.5, texture change had the best response out of the three variables we evaluated. The investigator determined that the mean improvement score for patients in group B's overall appearance was 5.61 ± 1.19. The study has shown that the combination of subcision with platelet-rich plasma, and microneedling appears to be a promising treatment for posttraumatic scars due to its low risk and high efficacy. Our findings suggest that this is a safe method for treating posttraumatic scars, with few side effects and a low chance of recurrence. IRB LOCAL APPROVAL NUMBER: 04-2023-300279. CLINICAL TRIAL REGISTRY: NCT06135480.

[Myocardial scar area predicts major adverse cardiovascular events after coronary artery bypass grafting in patients with ischemic cardiomyopathy].

Objective: To investigate the value of myocardium scar area in predicting adverse cardiovascular events (MACEs) after coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy (ICM). Methods: The first part of this study was a retrospective study. Patients diagnosed with ICM and undergoing CABG surgery at Beijing Anzhen Hospital, Capital Medical University from January 2017 to December 2022 were enrolled as the discovery cohort. All patients underwent cardiac magnetic resonance-late gadolinium enhancement (CMR-LGE) before surgery. According to the occurrence of postoperative MACEs, the patients were divided into MACEs group and MACEs-free group. Preoperative clinical and imaging data, intraoperative and postoperative data were collected and compared between the two groups. The primary endpoint was postoperative MACEs. Univariate and multifactor regression analyses were used to analyze the risk factors for MACEs. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive efficacy and optimal cut-off value of myocardial scar area for endpoint events. The second part of this study was a prospective study. Patients with ICM who received CABG at Beijing Anzhen Hospital, Capital Medical University from January 2023 to June 2023 were enrolled as a validation cohort, and were divided into MACEs group and MACEs-free group according to whether MACEs occurred after surgery. Preoperative clinical and imaging data, intraoperative and postoperative data were collected and compared between the two groups. Verify the reliability of the cut-off value obtained by ROC curve in the validation cohort. Results: A total of 120 patients with ICM (30 patients in MACEs group and 90 patients in MACEs-free group), aged (61.6±8.7) years, including 93 males, were included in the discovery cohort. A total of 22 ICM patients (5 patients in MACEs group and 17 patients in MACEs-free group), aged (59.5±8.2) years, including 18 males, were included in the validation cohort. Multivariate Cox regression showed that myocardial scar area (HR=1.258, 95%CI 1.096-1.444, P=0.001) was an independent risk factor for the primary endpoint event. The area under ROC curve of myocardial scar area for predicting postoperative MACEs was 0.90 (95%CI 0.83-0.95), and myocardial scar area≥36.0% was the optimal cut-off value for predicting postoperative MACEs, and its sensitivity, specificity and accuracy were 96.7%, 72.2% and 78.3%, respectively. In the validation cohort, the sensitivity, specificity and accuracy of myocardial scar area in predicting postoperative MACEs in patients with ICM after CABG were 80.0%, 82.4% and 81.8%, respectively. Conclusion: Myocardial scar area is an independent risk factor for MACEs after CABG in patients with ICM, and myocardial scar area≥36.0% is the optimal cut-off value for predicting MACEs after CABG. Myocardial scar area can help to identify patients at high risk of surgery and provide a basis for risk stratification of patients.

[Non-standard long-term tracheal stenting with silicone endoprosthesis for cicatricial stenosis]. / Nestandartnoe dlitel'noe stentirovanie trakhei silikonovym endoprotezom pri rubtsovom stenoze.

Endoscopic approach with recanalization and stenting is one of the methods for cicatricial tracheal stenosis. Major complications may occur if service life of stents is not observed. However, there are currently no clear timing for stenting. In world practice, there are no indications on lifelong stenting for cicatricial tracheal stenosis. Restenosis is more common after stent removal and requires repeated stenting or another treatment. In case of prolonged stenting, silicone stent should be periodically replaced with a similar one due to destruction of silicone rubber. As a rule, this maneuver is necessary after 1-3 years. Currently, there is no information about maximum allowable duration of stent without replacement and possible complications. Condition of trachea after prolonged stenting is also unknown. We present long-term (27 years) tracheal stenting with a silicone stent. Stent fragmentation and dislocation throughout this period led to respiratory failure and emergency removal. Tracheal lumen was satisfactory immediately after procedure. However, restenosis appeared after 1.5 months and required endoscopic dilation with discussion of appropriate treatment option. However, the patient refused tracheal resection with anastomosis and underwent repeated stenting with similar stent and favorable immediate result.

Macrophages Modulate Optic Nerve Crush Injury Scar Formation and Retinal Ganglion Cell Function.

Purpose: Optic nerve (ON) injuries can result in vision loss via structural damage and cellular injury responses. Understanding the immune response, particularly the role of macrophages, in the cellular response to ON injury is crucial for developing therapeutic approaches which affect ON injury repair. The present study investigates the role of macrophages in ON injury response, fibrotic scar formation, and retinal ganglion cell (RGC) function. Methods: The study utilizes macrophage Fas-induced apoptosis (MaFIA) mice to selectively deplete hematogenous macrophages and explores the impact macrophages have on ON injury responses. Histological and immunofluorescence analyses were used to evaluate macrophage expression levels and fibrotic scar formation. Pattern electroretinogram (PERG) recordings were used to assess RGC function as result of ON injury. Results: Successful macrophage depletion was induced in MaFIA mice, which led to reduced fibrotic scar formation in the ON post-injury. Despite an increase in activated macrophages in the retina, RGC function was preserved, as demonstrated by normal PERG waveforms for up to 2 months post-injury. The study suggests a neuroprotective role for macrophage depletion in ON damage repair and highlights the complex immune response to ON injury. Conclusions: To our knowledge, this study is the first to use MaFIA mice to demonstrate that targeted depletion of hematogenous macrophages leads to a significant reduction in scar size and the preservation of RGC functionality after ON injury. These findings highlight the key role of hematogenous macrophages in the response to ON injury and opens new avenues for therapeutic interventions in ON injuries. Future research should focus on investigating the distinct roles of macrophage subtypes in ON injury and potential macrophage-associated molecular targets to improve ON regeneration and repair.

Evaluating the impact of a trial of labor after cesarean section on labor duration: a retrospective cohort study.

BACKGROUND: Cesarean section (C-section) rates are increasing globally, and repeated C-sections are associated with increased maternal morbidity. Trial of labor after C-section (TOLAC) is an approach to reduce the recurrence of C-sections. However, limited research exists on the impact of cesarean scars on labor duration in TOLAC, considering the termination of labor through C-section and selection bias. This study aimed to investigate the impact of cesarean scars on labor duration in TOLAC participants, accounting for potential confounding factors and biases. METHODS: This retrospective cohort study included 2,964 women who attempted vaginal birth at a single center in Japan from 2012 to 2021. The study categorized participants into TOLAC (n = 187) and non-TOLAC (n = 2,777) groups. Propensity scores were calculated based on 14 factors that could influence labor duration, and inverse probability of treatment weighting (IPTW) was applied. Cox proportional hazards regression analysis estimated hazard ratios (HRs) for labor duration, with and without IPTW adjustment. Sensitivity analyses used propensity score matching, bootstrapping, and interval censoring to address potential biases, including recall bias in the reported onset of labor. RESULTS: The unadjusted HR for labor duration in the TOLAC group compared to the non-TOLAC group was 0.83 (95% CI: 0.70-0.98, P = 0.027), indicating a longer labor duration in the TOLAC group. After adjusting for confounding factors using IPTW, the HR was 0.98 (95% CI: 0.74-1.30, P = 0.91), suggesting no significant difference in labor duration between the groups. Sensitivity analyses using propensity score matching, bootstrapping, and interval censoring yielded consistent results. These findings suggested that the apparent association between TOLAC and longer labor duration was because of confounding factors rather than TOLAC itself. CONCLUSIONS: After adjusting for confounding factors and addressing potential biases, cesarean scars had a limited impact on labor duration in TOLAC participants. Maternal and fetal characteristics may have a more substantial influence on labor duration.

Automated cardiovascular MR myocardial scar quantification with unsupervised domain adaptation.

Quantification of myocardial scar from late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) images can be facilitated by automated artificial intelligence (AI)-based analysis. However, AI models are susceptible to domain shifts in which the model performance is degraded when applied to data with different characteristics than the original training data. In this study, CycleGAN models were trained to translate local hospital data to the appearance of a public LGE CMR dataset. After domain adaptation, an AI scar quantification pipeline including myocardium segmentation, scar segmentation, and computation of scar burden, previously developed on the public dataset, was evaluated on an external test set including 44 patients clinically assessed for ischemic scar. The mean ± standard deviation Dice similarity coefficients between the manual and AI-predicted segmentations in all patients were similar to those previously reported: 0.76 ± 0.05 for myocardium and 0.75 ± 0.32 for scar, 0.41 ± 0.12 for scar in scans with pathological findings. Bland-Altman analysis showed a mean bias in scar burden percentage of -0.62% with limits of agreement from -8.4% to 7.17%. These results show the feasibility of deploying AI models, trained with public data, for LGE CMR quantification on local clinical data using unsupervised CycleGAN-based domain adaptation. RELEVANCE STATEMENT: Our study demonstrated the possibility of using AI models trained from public databases to be applied to patient data acquired at a specific institution with different acquisition settings, without additional manual labor to obtain further training labels.

[The use of the dura mater at the final stage of reconstructive plastic surgical treatment of cicatricial stenosis of the larynx and trachea]. / Ispol'zovanie tverdoi mozgovoi obolochki pri zaklyuchitel'nom etape rekonstruktivno-plasticheskogo operativnogo lecheniya rubtsovogo stenoza gortani i trakhei.

The article presents an analysis of the plastic reconstructive surgery effectiveness for patients with an extended tracheal defect using an allograft based on the dura mater (DM) at the final stage of surgical treatment of laryngeal and tracheal cicatricial stenosis. The study included 20 patients with cicatricial stenosis of the larynx and trachea, who were previously performed plastic reconstructive treatment with scar tissue excision in the lumen of the respiratory tract and restoration of the supporting frame of the larynx and trachea using allografts based on costal allocartilage. The age of the patients ranged from 21 to 54 years, the duration of the disease was from 1 to 5 years. After a standard clinical and laboratory examination, with a mandatory video endoscopic examination of the larynx and trachea, multislice computed tomography of the larynx and trachea, patients underwent plastic closure of the tracheal defect using DM. Dynamic outpatient monitoring was carried out once a week for 1 month, once a month for 3 months, control examination was done 6 months after surgical treatment. The results of the study demonstrated a full-fledged social and labor rehabilitation of all 20 patients after the final stage of surgical treatment using DM, the absence of rejection reaction and migration of allo-implantation material, the preserved lumen of the larynx and trachea with a rigid supporting skeleton and the absence of anterior tracheal wall floatation. The use of DM as an additional strengthening of the anterior tracheal wall for patients with deficiency of muscular aponeurotic tissues and more than 2 cm size tracheal defect is highly effective at the final stage of surgical treatment for plastic closure of the tracheal defect.

Lactate promotes microglial scar formation and facilitates locomotor function recovery by enhancing histone H4 lysine 12 lactylation after spinal cord injury.

Lactate-derived histone lactylation is involved in multiple pathological processes through transcriptional regulation. The role of lactate-derived histone lactylation in the repair of spinal cord injury (SCI) remains unclear. Here we report that overall lactate levels and lactylation are upregulated in the spinal cord after SCI. Notably, H4K12la was significantly elevated in the microglia of the injured spinal cord, whereas exogenous lactate treatment further elevated H4K12la in microglia after SCI. Functionally, lactate treatment promoted microglial proliferation, scar formation, axon regeneration, and locomotor function recovery after SCI. Mechanically, lactate-mediated H4K12la elevation promoted PD-1 transcription in microglia, thereby facilitating SCI repair. Furthermore, a series of rescue experiments confirmed that a PD-1 inhibitor or microglia-specific AAV-sh-PD-1 significantly reversed the therapeutic effects of lactate following SCI. This study illustrates the function and mechanism of lactate/H4K12la/PD-1 signaling in microglia-mediated tissue repair and provides a novel target for SCI therapy.

[TruClear™ treatment of caesarean scar pregnancy interrupted after methotrexate injection]. / Résection mécanique hystéroscopique de résidus trophoblastique d'une grossesse sur cicatrice de césarienne après injection de méthotrexate.

BACKGROUND: Cesarean scar pregnancy is a complicated and potentially life-threatening type of ectopic pregnancy. There is no gold standard for its management. The aim is to demonstrate the efficacy and safety of treatment by hysteroscopic tissue removal system after systemic methotrexate injection. METHODS: We report the case of a 27-year-old patient who had previously had a C-section and who presented herself to the emergency room with pelvic pain and metrorrhagia. The human chorionic gonadotrophin (hCG) serum level was positive. The exploration revealed an ectopic pregnancy on the cesarean scar. She benefited of 4 systemic injections of methotrexate. As the hCG became negative, endovaginal ultrasound confirmed the avascular nature of the mass. Surgical resection by mechanical morcellation hysteroscopy (TruClear™) was performed under general anaesthesia, visual control and ultrasound guidance. RESULTS: This procedure was successful. It was an ambulatory procedure and there were neither intra- nor postoperative complications. CONCLUSIONS: To our knowledge, this is the first time in Belgium that a hysteroscopic tissue removal system procedure has been used to treat a caesarean scar pregnancy. This technique seems to be safe for both the patient and the surgeon and could become a new approach for cesarean scar pregnancy management.

CONTEXTE: La grossesse sur cicatrice de césarienne est définie comme la présence d'un sac gestationnel dans une isthmocèle créée par une hystérotomie préalable. Il n'existe pas de gold standard concernant sa prise en charge. L'objectif est de démontrer l'efficacité et la sécurité du traitement par résection mécanique hystéroscopique des tissus après injection systémique de méthotrexate. Méthodes : Nous rapportons le cas d'une patiente de 27 ans ayant déjà eu une césarienne et qui s'est présentée aux urgences avec des douleurs pelviennes et des métrorragies. L'exploration révèle une grossesse sur la cicatrice de césarienne. Elle a bénéficié de 4 injections systémiques de méthotrexate. La résection des résidus trophoblastiques avasculaires a été réalisée par voie hystéroscopique en utilisant l'hystéroscope par action mécanique de type -TruClear™ et ce, sous contrôle échographique concomitant. Résultats : Cette procédure ambulatoire effectuée sous anesthésie générale a été un succès. Il n'y a eu aucune complication per- ou postopératoire. CONCLUSIONS: À notre connaissance, c'est la première fois qu'une résection par action mécanique des résidus trophoblastiques sur cicatrice de césarienne est réalisée en Belgique. Cette technique semble sûre pour la patiente et le chirurgien et pourrait devenir une nouvelle approche pour la prise en charge d'une grossesse sur cicatrice de césarienne.

A big bang theory of big brain trauma.

One of the biggest neurophysiological science news headlines of the 2024 summer reported a critical link between post-traumatic stress disorder (PTSD), suicide, and brain injury from blast events in members of the elite US fighting force, Navy SEALS. Researchers from the Department of Defense/Uniformed Services University Brain Tissue Repository (DOD/USU BTR) had discovered a border of neural damage between the layers of white and gray matter comprising the cortical folds of service members' brains. Described as a distinctive anatomical line of astroglial scarring along the shared junctions of gray and white cellular zones of the brain, this tissue injury was unlike that observed for concussive brain trauma. Rather, it was consistent with blast biophysics of mammalian tissues. In this new study, the damage appears to be correlated with long-term, repeated exposure to blast waves from nearby explosions or firing weapons. A cascade of progressive unexplained behaviors, cognitive decline, and severe depression in the trained fighters ensued. This analysis suggested that repetitive, impulsive pressure waves traveling through the service members' heads and brains with each blast had compromised their cognitive centers, setting a downward trajectory in their mental and physical health.

[Application of modified Z-shaped cosmetic incision in parotid benign tumor resection].

Objective:To explore the safety and aesthetic effect of modified Z-shaped cosmetic incision in parotid benign tumor resection. Methods:A prospective study was conducted. A total of 44 patients with benign parotid tumor resection were randomly divided into experimental group（n=22） and control group（n=22）. The experimental group underwent modified Z-shaped cosmetic incision, while the control group underwent the traditional S-shaped incision. The surgical duration, hospital stay, complications and maxillofacial aesthetics were compared between the two groups. Results:There was no significant difference in gender, age, surgical method, pathological type between the experimental group and the control group（P>0.05）. The maxillofacial aesthetics and surgical duration of the two groups was statistically significant（P<0.05）, while there was no statistically significant difference in terms of hospitalization days, surgical complications and Vancouver scar scale score （P>0.05）. Conclusion:The modified Z-shaped cosmetic incision has a better effect on improving the maxillofacial aesthetics after benign parotid tumor resection, and compared with the traditional S-shaped incision, the safety is consistent, so it is worthy of clinical promotion and application.

Objective Analysis of Predictive Value of Ultrasound Quantitative Scoring System for Treatment Method Selection in Cesarean Scar Pregnancy.

ABSTRACT: This study aimed to explore the feasibility of using the ultrasound quantitative scoring system to guide the selection of surgical methods for a cesarean scar ectopic pregnancy (CSEP). A retrospective analysis was conducted of the medical records of 117 cases of patients with a CSEP. All patients underwent transvaginal ultrasound examination before treatment, and the ultrasound results were compared with the results of surgical exploration. The treatment methods that were delivered for the 2 patient groups with CSEP were analyzed, and agreement between the predicted and actual treatment protocols was tested using the kappa consistency test. Residual myometrial thickness at the scar site was mainly concentrated above 3 mm in the low-risk group, with 70 cases accounting for 76.9%, while in the high-risk group, this was primarily in the range of 1-3 mm with 18 cases accounting for 69.2%. The grading of nourishing blood supply to the gestational sac showed that 96.7% of patients in the low-risk group had Grade I and Grade II blood flow, while 84.6% of the high-risk group had Grade I and Grade II blood flow; Grade II blood flow was predominant in the high-risk group. The majority of patients in both the low- and high-risk groups experienced intraoperative blood loss of ≤50 mL (93.9% vs 80.6%, respectively). The consistency test between the actual and predicted treatment methods yielded a kappa coefficient of 0.644, indicating consistency between the two. For patients with CSEP in the low-risk group (score <4), the ultrasound quantitative scoring system could provide individualized assessment and offer clinically valuable treatment protocols.

Advances in the Application of Noninvasive Skin Imaging Techniques in Acne Scars.

Acne scarring is a common sequela of acne vulgaris, which seriously affects facial esthetics. The treatment options for acne scars vary depending on the development stage, color, type, and location of scarring. The objective and precise assessment of acne scars is a prerequisite for treatment, and it is also an important means of monitoring the treatment effect. The traditional methods to evaluate the types and severity grade of acne scars are primarily based on subjective assessment by physicians, which lacks objectivity and accuracy. Novel noninvasive skin imaging techniques, such as skin surface imaging analysis systems, dermoscopy, reflectance confocal microscopy (RCM), high-frequency ultrasound (HFUS), optical coherence tomography (OCT), and multiphoton tomography (MPT), provide new tools for the rapid and objective assessment of acne scars. This article reviews the progress of skin imaging techniques in the diagnosis, classification, and efficacy evaluation of acne scars.

Verapamil inhibits inflammation and promotes autophagy to alleviate ureteral scar by regulation of CaMK IIδ/STAT3 axis.

BACKGROUND: Ureteral stricture (US) is a pathological stenosis in the urinary tract characterized by increased collagen synthesis and inflammation. Autophagy activation has been shown to ameliorate tissue fibrosis and protect against fibrotic diseases. Verapamil has beneficial therapeutic benefits on fibrotic disorders. The pharmacological effects of verapamil on fibroblast autophagy in US and the underlying mechanism need to be investigated further. METHODS: US patients were recruited to isolate scar tissues, hematoxylin-eosin (HE) and Masson trichrome staining were performed to analyze histopathological changes. The US animal model was established and administered with verapamil (0.05 mg/kg) in the drinking water. Transforming growth factor (TGF)-ß1 was adopted to facilitate collagen synthesis in fibroblasts. The mRNA and protein expressions were examined by qRT-PCR, western blot, immunofluorescence and immunohistochemistry. ELISA was adopted to measure interleukin (IL)-1ß and IL-6 levels. Molecular interaction experiments like dual luciferase reporter and chromatin immunoprecipitation (ChIP) assays were performed to analyze the interaction between signal transducers and activators of transcription 3 (STAT3) and RNA polymerase II associated factor 1 (PAF1). RESULTS: Herein, our results revealed that verapamil activated TGF-ß1-treated fibroblast autophagy and inhibited inflammation and fibrosis by repressing Ca2+/calmodulin-dependent protein kinase II (CaMK II) δ-mediated STAT3 activation. Our following tests revealed that STAT3 activated PAF1 transcription. PAF1 upregulation abrogated the regulatory effect of verapamil on fibroblast autophagy and fibrosis during US progression. Finally, verapamil mitigated US in vivo by activating fibroblast autophagy. CONCLUSION: Taken together, verapamil activated TGF-ß1-treated fibroblast autophagy and inhibited fibrosis by repressing the CaMK IIδ/STAT3/PAF1 axis.