Correlation between initial serum 25-hydroxyvitamin D and granulation growth in diabetic foot ulcers.

OBJECTIVE: To determine the correlation between initial serum 25-hydroxyvitamin D (25(OH)D) levels with granulation growth in diabetic foot ulcers (DFUs) after 21 days of treatment. METHOD: This cohort study involved patients with type 2 diabetes who had a DFU treated at hospital. Blood samples were taken from patients on admission. The chemiluminescent immunoassay technique was used to measure 25(OH)D levels. Granulation tissue growth was analysed by comparing the photographs from the initial treatment to day 21 of treatment. RESULTS: The median value of 25(OH)D levels at initial treatment was 8 ng/ml. The result showed no correlation between 25(OH)D levels and the granulation growth in DFUs (p=0.86). CONCLUSION: The initial serum 25(OH)D level was not correlated with the growth of granulation tissue in DFUs.

The Best Protocol to Treat Equine Skin Wounds by Second Intention Healing: A Scoping Review of the Literature.

Equine skin wound treatment continues to be a challenge for veterinarians. Despite being a frequent practice, it remains difficult to choose an evidence-based treatment protocol. This study aimed to comprehensively explore the literature and provide a scoping review of therapeutic strategies for equine skin wounds and identify knowledge gaps and opportunities for future research. This review was conducted using specific criteria to select literature that described methods to manage second intention wound healing. After removing duplicates and screening papers for suitability, 81 manuscripts were included for data extraction. Of these, 59 articles were experimental studies, 10 were case reports, 9 were case series, and 3 were clinical studies. The most frequent wound location was the distal limbs. Macroscopic assessment was the main tool used to evaluate treatment effectiveness. All of the case reports, case series, and clinical studies reported positive outcomes with regard to the treatment used, while only 36% of the experimental studies found significant healing improvement in treated wounds compared to control groups. It was found that there are many treatments that have exhibited controversial results, and there exists a lack of evidence for the adoption of specific treatment protocols.

Gene expression profiles in COVID-19-associated tracheal stenosis indicate persistent anti-viral response and dysregulated retinol metabolism.

INTRODUCTION: Coronavirus disease 2019 (COVID-19)-associated tracheal stenosis (COATS) may occur as a result of prolonged intubation during COVID-19 infection. We aimed to investigate patterns of gene expression in the tracheal granulation tissue of patients with COATS, leverage gene expression data to identify dysregulated cellular pathways and processes, and discuss potential therapeutic options based on the identified gene expression profiles. METHODS: Adult patients (age ≥ 18 years) presenting to clinics for management of severe, recalcitrant COATS were included in this study. RNA sequencing and differential gene expression analysis was performed with transcriptomic data for normal tracheal tissue being used as a control. The top ten most highly upregulated and downregulated genes were identified. For each of these pathologically dysregulated genes, we identified key cellular pathways and processes they are involved in using Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) applied via Database for Annotation, Visualization, and Integrated Discovery (DAVID). RESULTS: Two women, aged 36 years and 37 years, were included. The profile of dysregulated genes indicated a cellular response consistent with viral infection (CXCL11, PI15, CCL8, DEFB103A, IFI6, ACOD1, and DEFB4A) and hyperproliferation/hypergranulation (MMP3, CASP14 and HAS1), while downregulated pathways included retinol metabolism (ALDH1A2, RBP1, RBP4, CRABP1 and CRABP2). CONCLUSION: Gene expression changes consistent with persistent viral infection and dysregulated retinol metabolism may promote tracheal hypergranulation and hyperproliferation leading to COATS. Given the presence of existing literature highlighting retinoic acid's ability to favorably regulate these genes, improve cell-cell adhesion, and decrease overall disease severity in COVID-19, future studies must evaluate its utility for adjunctive management of COATS in animal models and clinical settings.

Optimizing clinical outcomes for bronchoscopic lung volume reduction with Zephyr® valves.

Bronchoscopic lung volume reduction treatment with Zephyr one-way valves is an effective guideline-based treatment option for patients with severe emphysema and hyperinflation. However, in some cases the treatment response is less than anticipated or there might be a loss of initial treatment effect. Reasons for the lack of response can include incorrect assessment of collateral ventilation, improper valve placement, or patient related factors. Loss of initial benefit can be due to granulation tissue formation and subsequent valve dysfunction, or there may be side effects such as excessive coughing or infectious problems. Careful follow-up after treatment with valves is important and evaluation with a CT scan and/or bronchoscopy is helpful if there is no improvement after treatment or loss of initial benefit. This paper aims to describe the most important causes and provide a strategy of how to approach and manage these patients.

Comparative Effectiveness of Negative Pressure Wound Therapy with and Without Oxidized Regenerated Cellulose/Collagen/Silver-ORC Dressing.

Objective: Negative pressure wound therapy (NPWT) and oxidized regenerated cellulose (ORC)/collagen/silver-ORC (OCSO) dressings have individually demonstrated effectiveness in supporting wound healing, but few studies have examined their combined use. This retrospective data analysis compared wound outcomes following outpatient NPWT with and without OCSO dressings. Approach: A search of deidentified records from the U.S. Wound Registry resulted in 485 cases of wounds managed with NPWT with OCSO dressings. A matched cohort of patients who received NPWT without any collagen dressing (n = 485) was created using propensity scoring. For patients in the NPWT + OCSO group, OCSO was applied topically on or after the day of NPWT initiation and stopped on or before the day of NPWT termination. Results: Wounds managed with NPWT + OCSO were significantly more likely to improve and/or heal compared with wounds that received NPWT alone (p = 0.00029). The relative wound area reduction was 40% for patients receiving NPWT + OCSO, compared with 9% for patients receiving only NPWT (p = 0.0099). The median time to achieve 75-100% granulation coverage with no measurable wound depth was shorter by 8 days with NPWT + OCSO in all wound types (p = 0.00034), and by 14 days in surgical wounds (p = 0.0010), than with NPWT alone. Innovation: This is the first study examining the clinical outcomes associated with the integration of NPWT and OCSO dressings compared with the use of NPWT alone. These data support the novel practice of applying NPWT concurrently with OCSO dressings. Conclusion: This retrospective comparative analysis using real-world data demonstrated improved healing outcomes with integrated use of NPWT with OCSO dressings versus NPWT alone.

A Comparative Study of Endoscopic Endonasal Dacryocystorhinostomy Using an Inferiorly Based Flap Versus a Posteriorly Based Flap.

To evaluate the outcome and complications of Endoscopic endonasal Dacryocystorhinostomy (DCR) using an inferiorly based mucosal flap as compared to a conventional posteriorly based mucosal flap with flap preservation and no stenting. 36 patients presenting with nasolacrimal duct obstruction were divided into two groups: the first group underwent endoscopic DCR using an inferiorly based mucosal flap, and the other group used a posteriorly based mucosal flap. In both groups, the mucosal flap was preserved, and bone was removed using Kerrison's punch. No stenting was done in any of the cases. The patency of the ostia was determined by syringing, and nasal endoscopy was done to look at the neo-ostium at follow-up visits to determine success and complications in each group. All 18 cases in the inferiorly based flap group had patent ostia with good mucosalization of the neo-ostium at 6-month follow-up. 3 of the 18 cases in the conventional posteriorly based flap group had failure due to granulation tissue formation around the neo-ostium. The use of an inferiorly based mucosal flap is easy to fashion and reposition at the end of the surgery. This technique has a good outcome with patent ostia during the follow-up period of 6 months.

Utility of solid area diameter in management of cystic papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) with marked cystic formation (CPTC) is not a subtype of PTC, and its clinical characteristics have not been fully investigated. This study aimed to clarify the clinical and pathological characteristics of CPTC and propose important indicators for its clinical management. Thirty-three CPTC nodules with cystic areas occupying >50% of their volume were examined. Two matched controls (MCs) were prepared, one with tumor diameter matched for whole tumor diameter (WTD) of CPTCs and the other with tumor diameter matched for solid area diameter (SAD) of CPTCs. The mean age of patients with CPTC was 55.2 years significantly older than that in SAD-MCs. Of the CPTCs, 69.7% were classified as highly suspicious by ultrasonography, and the prevalence was lower than that in WTD-MCs (88.9%) and SAD-MCs (91.5%). Total thyroidectomy was performed in 69.7% of CPTC cases, which was significantly less frequent than that in WDT-MCs (91.7%) and similar to that in SAD-MCs (76.1%). Histologically, CPTCs exhibited two characteristic findings: invasion from the solid area into the surrounding normal thyroid tissue and granulation tissue around the cystic wall. The frequencies of the cases with pathological lateral node metastasis, extrathyroidal extension, and Ki-67 labeling index ≥5% in CPTCs were significantly lower than those in WTD-MCs and relatively similar to those in SAD-MCs. In the surgical strategy and prognosis of CPTC, the evaluation of tumor size should be based on SAD rather than on WTD. We advocate measuring not only WTD but also SAD in CPTC.

Correlation between inflammatory factors, autophagy protein levels, and infection in granulation tissue of diabetic foot ulcer.

OBJECTIVE: To observe the expression of inflammatory factors and autophagy-related proteins in granulation tissue of diabetic foot ulcer (DFU) patients and analyze their relationship with infection. METHODS: This is a retrospective cohort study. One hundred and fifty-two patients with DFU in our hospital from July 2020 to March 2022 were selected as the DFU group, including 98 cases in infection stage group and 54 cases in infection control group. The patients were further graded as the mild (51 cases), the moderate (65 cases), and the severe infection group (36 cases) according to the Wagner grading criteria. Sixty-seven patients with foot burns during the same period were selected as the control group. The distribution of pathogenic bacteria on the ulcer surface was examined using fully automated bacterial analyzer. The expression of inflammatory factors (procalcitonin [PCT], tumor necrosis factor-α [TNF-α], and interleukin-6 [IL-6]) was valued by real-time fluorescence quantitative PCR (qRT-PCR). Protein expression was measured by immunohistochemistry (IHC). The correlation was analyzed by Pearson. RESULTS: The surface infection of DFU patients was mostly induced by gram-negative and gram-positive bacteria, with Pseudomonas aeruginosa predominating among the Gram-negative bacteria and Staphylococcus aureus among the gram-positive bacteria. The infection stage group had higher content of PCT, TNF-α, and IL-6 and lower content of Beclin-1 and LC3 than the infection control group (p < .001). The levels of PCT, TNF-α, and IL-6 in the DFU patients with cardiovascular events were higher than those in the nonoccurrence group (p < .001). Glycated hemoglobin in patients with DFU was positively correlated with PCT, TNF-α, and IL-6 levels (p < .05), and negatively correlated with Beclin-1 and LC3 levels (p < .001). CONCLUSION: P. aeruginosa and S. aureus were predominant bacterial in DFU infections. Inflammatory factor and autophagy protein expression were closely correlated with the degree of infection.

Autophagy Genes and Otitis Media Outcomes.

Otitis media (OM) is a common cause of hearing loss in children that requires corrective surgery. Various studies have investigated the pathomechanisms and treatment of OM. Autophagy, an essential cellular recycling and elimination mechanism implicated in various diseases, is known to play an important role in the pathogenesis of OM. Here, we conducted a literature review on autophagy in OM, highlighting the relationship between expression patterns of autophagy-related factors and pathophysiological and clinical aspects of OM. We summarized the existing research results on the expression of autophagy-related factors in acute OM (AOM), OM with effusion (OME), chronic OM (COM) with cholesteatoma, and COM without cholesteatoma (CholeOM) in animals and humans. Autophagy-related factors are expressed in the middle ear mucosa or fluid of AOM, effusion of OME, granulation tissue of COM, and cholesteatoma of CholeOM. Among ATGs and other autophagy-related factors, the most extensively studied in relation to the pathogenesis of OM are mTOR, LC3II/I, PI3K, Beclin-1, FLIP, Akt, and Rubicon. Expression of autophagy-related factors is associated with AOM, OME, COM, and CholeOM. Inadequate expression of these factors or a decrease/increase in autophagy responses can result in OM, underscoring the critical role of ATGs and related factors in the pathogenesis of OM.

Granulation tissue-like spindle cell (sarcomatoid) carcinoma of the head and neck: a deceptively bland-looking underdiagnosed malignancy.

The diagnosis of head and neck spindle cell squamous carcinoma (SC-SCC) is often challenging. Lesions with a prominent inflammatory infiltrate and reactive vessels may have a granulation tissue-like appearance, therefore being difficult to distinguish from reactive lesions, like contact ulcers, post-intubation granulomas, inflammatory pseudotumors, or benign vascular lesions. In this study, we analyzed the clinicopathological features of a series of 17 head and neck SC-SCC with granulation tissue-like appearance. All patients, but two, were males, ranging in age between 57 and 80 years. The larynx was the most frequently affected site (n = 12), followed by the tongue (n = 4). One tumor was hypopharyngeal. Most consult cases were submitted with benign suggestion or because of unexpected recurrences of granulation tissue polyps. Histologically, all lesions consisted of an ulcerated polypoid proliferation of moderately to markedly atypical spindle cells, with a minor component of conventional invasive or in situ squamous carcinoma. At least one cytokeratin cocktail was positive in 13 cases. The staining was limited to a few neoplastic cells in most cases. Positivity for p63, p40, and cytokeratins 5/6 was detected only in the conventional squamous cell carcinoma component, when present. ALK1 was negative in all cases. Sixteen cases were tested for p53 and all showed aberrant expression (12 diffusely positive and 4 of null-phenotype). The diagnosis of granulation tissue-like SC-SCC is challenging due to the close clinical and histological overlap with several benign conditions. Since the expression of epithelial markers is limited, the use of an immunohistochemical panel including p53 is recommended.

A new lymphedema treatment using pyro-drive jet injection.

Lymphedema, resulting from impaired lymphatic drainage, causes inflammation, fibrosis and tissue damage leading to symptoms such as limb swelling and restricted mobility. Despite various treatments under exploration, no standard effective therapy exists. Here a novel technique using the pyro-drive jet injection (PJI) was used to create artificial clefts between collagen fibers, which facilitated the removal of excess interstitial fluid. The PJI was used to deliver a mixture of lactated Ringer's solution and air into the tail of animals with secondary skin edema. Edema levels were assessed using micro-CT scanning. Histopathological changes and neovascularization were evaluated on the injury-induced regenerative tissue. Regarding tissue remodeling, we focused on connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF)-C. PJI markedly diminished soft tissue volume in the experimental lymphedema animals compared to the non-injected counterparts. The PJI groups exhibited a significantly reduced proportion of inflammatory granulation tissue and an enhanced density of lymphatic vessels and α-smooth muscle actin (αSMA)-positive small vessels in the fibrous granulation tissue compared to the controls. In addition, PJI curtailed the prevalence of CTGF- and VEGF-C-positive cells in regenerative tissue. In a lymphedema animal model, PJI notably ameliorated interstitial edema, promoted lymphatic vessel growth, and bolstered αSMA-positive capillaries in fibrous granulation tissue. PJI's minimal tissue impact post-lymph node dissection indicates significant potential as an early, standard preventative measure. Easily applied in general clinics without requiring specialized training, it offers a cost-effective and highly versatile solution to the management of lymphedema.

Steroid-Eluting Implants: An Adjunctive Therapy After Double-Stage Laryngotracheal Reconstruction.

OBJECTIVES: The primary objective is to describe a case in which a steroid-eluting implant was utilized to help prevent postoperative granulation and restenosis in a patient who underwent double-stage laryngotracheal reconstruction (dsLTR) for subglottic stenosis. METHODS: This case presents a 3-year-old female who underwent dsLTR with anterior cartilage graft placement and posterior sagittal split for subglottic stenosis. A silicone stent was placed at the time of the dsLTR. After stent removal, direct laryngoscopy and bronchoscopy (DLB) was performed at 4 to 5 week intervals. These visits revealed a significant amount of supraglottic and glottic edema, and granulation tissue at the proximal aspect of the graft contributing to airway obstruction and restenosis. This was treated twice with CO2 laser excision, balloon dilation, and triamcinolone injection. On the third treatment with these modalities, a mometasone furoate implant was inserted as an adjunctive therapy. The implant was inserted to lateralize the vocal folds, prevent webbing, and to extend to the narrowed area within the subglottis to prevent granulation and restenosis. These same treatments were repeated at the fourth visit with another mometasone furoate implant of a smaller size placed in the same location. RESULTS: Findings on DLB since treatment with the steroid-eluting implants have shown persistent granulation tissue limited to the tracheostomy stoma site. Treatments with CO2 laser, balloon dilation, and triamcinolone injection have continued, with occasional use of silver nitrate cautery at the external stoma site. There has not been any significant evidence of edema, granulation, or stenosis in the glottis or subglottis to require another steroid-eluting implant. CONCLUSIONS: Steroid-eluting implants appear to be a safe and effective adjunctive therapy in the routine surveillance of pediatric patients with a tracheostomy who have undergone dsLTR. They may help combat granulation formation and restenosis seen in some dsLTR patients.

Prevalence of Chlamydia infection detected by immunohistochemistry in patients with anorectal ulcer and granulation tissue.

Anorectal ulcer with granulation tissue is typically associated with left-sided inflammatory bowel disease or infection. Due to emerging cases of Chlamydia proctitis, we aim to investigate the prevalence of Chlamydia infection using immunohistochemistry (IHC) in anorectal biopsies showing ulcer and granulation tissue. Seventy-seven patients including 60 males and 17 females with mean age of 51 years old were retrospectively identified in surgical pathology archives. Chlamydia IHC was validated with a monoclonal antibody on an index who was positive for Chlamydia by rectal swab nucleic acid amplification test (NAAT), then performed on formalin fixed and paraffin embedded (FFPE) tissue sections. Confirmative molecular test using real-time PCR was performed on DNA extractions of 14 IHC-positive and 14 IHC-negative FFPEs, 18 NAAT-positive, and 5 NAAT-negative cytology specimens. Chlamydia IHC showed strong intracytoplasmic or extracellular sphere morphology in 14 of 77 (18.2 %) FFPEs, including 11 of 60 (18.3 %) males and 3 of 17 (17.6 %) females (age 11-84 years). Eight of 14 (57.1 %) Chlamydia-IHC positive patients had known history of STDs, high-risk behavior, or immunosuppressive conditions. One of 14 (7.1 %) IHC-positive FFEP and 15 of 18 (83.3 %) NAAT-positive cytology cases were confirmed by real-time PCR. Chlamydia inclusions were detected in all 4 randomly selected NAAT and PCR-positive cytology specimens by IHC. Our data suggested that Chlamydia infection is more prevalent than we thought in patients with active proctitis and ulceration. Chlamydia IHC may be performed as a screening test in biopsies to facilitate early detection of this treatable proctitis in high-risk population.

Epalrestat is effective in treating diabetic foot infection and can lower serum inflammatory factors in patients.

This study was designed to determine the efficacy of epalrestat on patients with diabetic foot infection (DFI) and its effects on serum inflammatory factors in the patients. METHODS: The data of 80 patients with DFI treated in the First Affiliated Hospital of Jiangxi Medical College from May 2020 to May 2022 were analyzed retrospectively. Among them, patients who received routine comprehensive treatment were enrolled into the control group (n=37), and those who received epalrestat on the basis of routine comprehensive treatment were enrolled into the study group (n=43). The changes of serum inflammatory factors before and after treatment, granulation tissue grading and efficacy in the two groups were analyzed and compared, and the wound healing time, hospitalization time and adverse reactions (including nausea and vomiting, dizziness, headache, pruritus, etc.) of the two groups were statistically analyzed. The prognosis of the patients within 1 year after treatment was analyzed, and the independent risk factors of poor prognosis were analyzed through logistic regression. RESULTS: Before treatment, the two groups were not significantly different in the levels of tumor necrosis factor-α (TNF-α), high sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6), while after treatment, the levels decreased significantly in both groups, with significantly lower levels in the study group than those in the control group. The study group had a significant lower proportion of patients with grade 0/grade 1 granulation tissue than the control group, and had a significantly higher proportion of patients with grade 2/grade 4 granulation tissue than the control group, but the proportion of patients with grade 3 granulation tissue in the two groups was not greatly different. The study group experienced notably shorter wound healing time and hospitalization time than the control group. A notably higher overall response rate was found in the study group than that in the control group. In addition, the total incidence of adverse reactions was not greatly different between the two groups. BMI, diabetes mellitus type, Wagner grading and classification of diabetic foot infection were found to be the risk factors affecting the prognosis of patients, and Wagner grading was an independent risk factor affecting the prognosis of patients. CONCLUSION: Epalrestat is effective in treating DFI, because it can lower the levels of serum inflammatory factors, shorten the time of wound healing and hospitalization, and promote the growth and recovery of granulation, without increasing adverse reactions. Therefore, it is worthy of clinical promotion.

Evolving Role of Negative Pressure Wound Therapy with Instillation and Dwell Time (NPWTi-d-) in Management of Trauma and Orthopaedic Wounds: Mechanism, Applications and Future Perspectives.

Introduction: Negative Pressure Wound Therapy (NPWT) is a well-established method to promote wound healing by delivering negative pressure (a vacuum) at the wound site. Enhancement of NPWT techniques may allow an innovative way of treating trauma and orthopaedic wounds which provide unique challenges. We explore the role of negative pressure wound therapy with instillation and dwell time (NPWTi-d-) in the management of trauma and orthopaedic wounds. Materials and Methods: A comprehensive search strategy was conducted using databases of PubMed, Web of Science, Google Scholar, and Cochrane Library with the search words of 'NPWTid' or 'NPWTi-d-' or 'NPWT with instillation' or 'Negative pressure wound treatment with instillation' to generate this narrative review. The mechanism of action of NPWTi-d-, installation solutions and current applications in the trauma and orthopaedic wounds is evaluated. Results: NPWTi-d- provides additional mechanism to promote wound healing in a spectrum of acute and chronic orthopaedic wounds. The technique allows local delivery of hydration and elution of antibiotics to support growth of healthy granulation tissue. Various mechanism of actions contribute in drawing the wound edges together, reduce oedema, help decontamination, deliver local antibiotic and promote healing. Conclusion: NPWTi-d- permits an enhanced, supplementary technique to encourage wound healing in challenging traumatic and orthopaedic wounds. Future applications of NPWTi-d- will depend on cost-effectiveness analysis and development of its application guidelines based on longitudinal, randomized controlled research trials.

Preadipocytes in human granulation tissue: role in wound healing and response to macrophage polarization.

BACKGROUND: Chronic non-healing wounds pose a global health challenge. Under optimized conditions, skin wounds heal by the formation of scar tissue. However, deregulated cell activation leads to persistent inflammation and the formation of granulation tissue, a type of premature scar tissue without epithelialization. Regenerative cells from the wound periphery contribute to the healing process, but little is known about their cellular fate in an inflammatory, macrophage-dominated wound microenvironment. METHODS: We examined CD45-/CD31-/CD34+ preadipocytes and CD68+ macrophages in human granulation tissue from pressure ulcers (n=6) using immunofluorescence, immunohistochemistry, and flow cytometry. In vitro, we studied macrophage-preadipocyte interactions using primary human adipose-derived stem cells (ASCs) exposed to conditioned medium harvested from IFNG/LPS (M1)- or IL4/IL13 (M2)-activated macrophages. Macrophages were derived from THP1 cells or CD14+ monocytes. In addition to confocal microscopy and flow cytometry, ASCs were analyzed for metabolic (OXPHOS, glycolysis), morphological (cytoskeleton), and mitochondrial (ATP production, membrane potential) changes. Angiogenic properties of ASCs were determined by HUVEC-based angiogenesis assay. Protein and mRNA levels were assessed by immunoblotting and quantitative RT-PCR. RESULTS: CD45-/CD31-/CD34+ preadipocytes were observed with a prevalence of up to 1.5% of total viable cells in human granulation tissue. Immunofluorescence staining suggested a spatial proximity of these cells to CD68+ macrophages in vivo. In vitro, ASCs exposed to M1, but not to M2 macrophage secretome showed a pro-fibrotic response characterized by stress fiber formation, elevated alpha smooth muscle actin (SMA), and increased expression of integrins ITGA5 and ITGAV. Macrophage-secreted IL1B and TGFB1 mediated this response via the PI3K/AKT and p38-MAPK pathways. In addition, ASCs exposed to M1-inflammatory stress demonstrated reduced migration, switched to a glycolysis-dominated metabolism with reduced ATP production, and increased levels of inflammatory cytokines such as IL1B, IL8, and MCP1. Notably, M1 but not M2 macrophages enhanced the angiogenic potential of ASCs. CONCLUSION: Preadipocyte fate in wound tissue is influenced by macrophage polarization. Pro-inflammatory M1 macrophages induce a pro-fibrotic response in ASCs through IL1B and TGFB1 signaling, while anti-inflammatory M2 macrophages have limited effects. These findings shed light on cellular interactions in chronic wounds and provide important information for the potential therapeutic use of ASCs in human wound healing.

Anastomotic stenosis of bioengineered trachea grafts is driven by transforming growth factor ß1-induced signaling, proinflammatory macrophages, and delayed epithelialization.

Objective: Anastomotic stenosis caused by hypertrophic granulation tissue often develops in response to orthotopically implanted bioengineered tracheal grafts. To determine mechanisms responsible for the development and persistence of this granulation tissue, we looked for changes in gene expression from tissue specimens from the graft-native interface. Methods: RNA was isolated from paraffin-embedded tissue samples of the anastomotic sites of orthotopically implanted bioengineered tracheal grafts of 9 animals. Tissue samples were binned into 3 groups based on degree of stenosis: no stenosis (<5%), mild stenosis (25%-50%), and moderate and severe stenosis (≥75%). Sections of healthy trachea tissue were used as control. The expression levels of ∼200 genes related to wound healing, plus several endogenous controls, were measured with a pathway-focused predesigned primer array. Results: Expression of ARG2, IL4, RPL13 A, TGFBR3, and EGFR decreased, whereas expression of RUNX2 was increased in stenotic wounds compared with nonstenotic tissue. Based on the cell types present in the trachea and wound healing, this expression profile indicates a lack of M2 anti-inflammatory macrophages, absent epithelial cells, and transforming growth factor ß1-induced signaling. Conclusions: These findings represent a significant step for tracheal tissue engineering by identifying several key mechanisms present in stenotic granulation tissue. Further research must be conducted to determine what modifications of the graft substrate and which coadministered therapeutics can be used to prevent the development of hypertrophic granulation tissue.

Evaluation of Dental Professionals' Knowledge and Attitude Regarding the Diagnosis of Oral Cancer Through Histopathological Examination of Granulation Tissue.

INTRODUCTION: The current cancer trend in India has reported an alarming increase in cancer of the lip, throat, and oral cavity. Few dentists are aware that malignant neoplasms can also occur in the form of granulation tissue and periapical granulomas. However, most dentists agree that biopsies are essential to diagnose oral cancer. This makes the timely diagnosis of oral cancer dependent upon the histopathological examination of the granulation tissue by the dentist. AIM:  The main aim of this study was to evaluate the knowledge and attitudes of dentists regarding the diagnosis of oral cancer through histopathological analysis of granulation tissue. METHOD: A cross-sectional study was conducted on dentists who were residents of Uttar Pradesh, India. Two hundred and fifty study participants enrolled to complete a self-structured questionnaire containing 15 closed-ended questions. The study was conducted over a period of three months, from June to August 2020. Descriptive statistics were analyzed using IBM SPSS Statistics for Windows, Version 21.0 (Released 2012; IBM Corp., Armonk, New York, United States, and the t-test was performed. A significance level of P ≤ 0.05 was used to determine the statistical significance of quantitative variables. RESULTS: The study findings revealed that only a small percentage of dentists (47.2%) were aware of the importance of biopsies in diagnosing oral cancer. Moreover, a minority (14.4%) had conducted biopsies and submitted samples for histopathological analysis. Of them, 10% were aware that in clinical practice, malignant tumors can also manifest as periapical granulomas, granulation tissue, gingivitis, and other conditions. CONCLUSION: Dentists should proactively submit any granulation tissue for histopathological examination. Oral healthcare providers must maintain a high level of suspicion, develop a range of potential or differential diagnoses for oral cancer, and take necessary measures to attain a definitive diagnosis. This may include considering a referral to a specialist for the treatment of oral cancer.

Radiofrequency ablation via an implanted self-expandable metallic stent to treat in-stent restenosis in a rat gastric outlet obstruction model.

Background: In-stent restenosis caused by tissue hyperplasia and tumor growth through the wire meshes of an implanted self-expandable metallic stent (SEMS) remains an unresolved obstacle. This study aimed to investigate the safety and efficacy of SEMS-mediated radiofrequency ablation (RFA) for treating stent-induced tissue hyperplasia in a rat gastric outlet obstruction model. Methods: The ablation zone was investigated using extracted porcine liver according to the ablation time. The optimal RFA parameters were evaluated in the dissected rat gastric outlet. We allocated 40 male rats to four groups of 10 rats as follows: group A, SEMS placement only; group B, SEMS-mediated RFA at 4 weeks; group C, SEMS-mediated RFA at 4 weeks and housed until 8 weeks; and group D, SEMS-mediated RFA at 4 and 8 weeks. Endoscopy and fluoroscopy for in vivo imaging and histological and immunohistochemical analysis were performed to compare experimental groups. Results: Stent placement and SEMS-mediated RFA with an optimized RFA parameter were technically successful in all groups. Granulation tissue formation-related variables were significantly higher in group A than in groups B-D (all p < 0.05). Endoscopic and histological findings confirmed that the degrees of stent-induced tissue hyperplasia in group D were significantly lower than in groups B and C (all p < 0.05). Hsp70 and TUNEL expressions were significantly higher in groups B-D than in group A (all p < 0.001). Conclusion: The implanted SEMS-mediated RFA successfully managed stent-induced tissue hyperplasia, and repeated or periodic RFA seems to be more effective in treating in-stent restenosis in a rat gastric outlet obstruction model.

Predictive factors and clinical efficacy of Chinese medicine Shengji ointment in the treatment of diabetic foot ulcers in the elderly: a prospective study.

Objective: This study aims to investigate the predictive factors and efficacy of traditional Chinese medicine Shengji Ointment in the treatment of diabetic foot ulcers in the elderly population, with the intent of formulating an effective predictive model for deep diabetic foot ulcer healing. The importance of this research lies in its provision of new perspectives and tools for addressing the severe health impact of diabetic foot ulcers in the elderly population, considering the complexity and diversity of its treatment methods. Methods: The study includes 180 elderly patients with Wagner grade 3-4 diabetic foot ulcers that involve the tendon or fascia. The dependent variable is the initiation time of granulation tissue development. Independent variables encompass demographic information, a treatment strategy including Shengji Ointment, pre-treatment trauma assessment data, routine blood count, and biochemical index test results. Lasso regression is employed for variable selection, and Cox regression is utilized for the construction of a prediction model. A nomogram is generated to authenticate the model. Results: The Chinese Medicine treatment approach, ulcer location, creatinine levels, BMI, and haemoglobin levels are identified as independent predictors of granulation tissue development in diabetic foot ulcers. The combined treatment of Chinese herbal Shengji ointment and bromelain positively influenced granulation tissue development. The location of plantar ulcers, impaired renal functionality, obesity, and anaemia are established as independent risk factors that might influence the speed and probability of ulcer healing. The area under the time-dependent ROC curve fluctuates between 0.7 and 0.8, demonstrating substantial discrimination and calibration of the model. Conclusion: The study ascertains that a combined treatment strategy incorporating Shengji Ointment demonstrates greater effectiveness than the use of cleansing gel debridement alone in facilitating the healing of Wagner grade 3 or higher diabetic foot ulcers. Furthermore, the predictive model developed in this research serves as a valuable tool in evaluating the efficacy of Chinese Medicine treatments like Shengji Ointment for diabetic foot ulcers in the elderly. It aids clinicians in effectively assessing and adjusting treatment strategies, thereby proving its significant application value in clinical practice. Clinical Trial Registration: (https://www.chictr.org.cn/hvshowproject.html?id=73862&v=1.5&u_atoken=b403af53-d3b9-41ae-a7e2-db5498609b0c&u_asession=01tNh69p235bMUO4CmHIXcv8Hxirl5-557Duue9QB5lGfl3mf8IvPlcs2kN2zC30voX0KNBwm7Lovlpxjd_P_q4JsKWYrT3W_NKPr8w6oU7K_AyPrQhedMUWBMR2-ZDL_KO0uwDPR9XlF566xraDvT9mBkFo3NEHBv0PZUm6pbxQU&u_asig=05Kd_Q8fjv-24MVbZpOS9ef3xuCCN-tSVH5eUoJKgNLM7E0-n0zMpW6xLq9gh9aUhkKEEA15rdDoCydncF99APBwVSaTPgEG_V_B1iT4wimdCTxV_4ZVbTlDewxyQtE4YgU4-Oza7KPi94RJ64Utel0yZfqg3Tlm-bVxFNOY-zXFP9JS7q8ZD7Xtz2Ly-b0kmuyAKRFSVJkkdwVUnyHAIJzSYJ6SfhFl0WMTCCasZ7zV2I2qfyrp5m-SELPVeREKgX_6yRmLu26qT8kGfcS-Yaeu3h9VXwMyh6PgyDIVSG1W-7D_Sko5YQtpDbs3uvezYkZcUUY4o9-zDPaoYelmMDs8u7I4TPvtCXaPp44YUJcQ9bHr-_RmKA5V8nji3daArhmWspDxyAEEo4kbsryBKb9Q&u_aref=NNH1nHSUCE6pNvCilV%2F1MD0aERs%3D), identifier (ChiCTR2000039327).