Wound senescence: A functional link between diabetes and ageing?

Arguably, the two most important causes of pathological healing in the skin are diabetes and ageing. While these factors have historically been considered independent modifiers of the healing process, recent studies suggest that they may be mechanistically linked. The primary contributor to diabetic pathology is hyperglycaemia, which accelerates the production of advanced glycation end products, a characteristic of ageing tissue. Indeed, advanced age also leads to mild hyperglycaemia. Here, we discuss emerging literature that reveals a hitherto unappreciated link between cellular senescence, diabetes and wound repair. Senescent cells cause widespread destruction of normal tissue architecture in ageing and have been shown to be increased in chronic wounds. However, the role of senescence remains controversial, with several studies reporting beneficial effects for transiently induced senescence in wound healing. We recently highlighted a direct role for senescence in diabetic healing pathology, mediated by the senescence receptor, CXCR2. These findings suggest that targeting local tissue senescence may provide a therapeutic strategy applicable to a broad range of chronic wound types.     

Ketorolac plus Lidocaine vs Lidocaine for pain relief following core needle soft tissue biopsy: A CONSORT-compliant double-blind randomized controlled study

Backgrounds:The main objective of this study was to compare the pain control efficacy of local administration of Lidocaine with or without the nonsteroidal anti-inflammatory drug, Ketorolac, and local conventional Lidocaine injection in core needle biopsy of the musculoskeletal tumor.Methods:The current study was a randomized, double-blind controlled clinical trial that included 128 patients with suspected musculoskeletal tumors. Patients were randomly assigned to either the Ketorolac plus Lidocaine (n = 64) or Lidocaine group (n = 64). The Ketorolac – Lidocaine combination syringe contained 30 mg Ketorolac and 2% Lidocaine – adrenaline dosage, and the Lidocaine syringe contained 2% Lidocaine – adrenaline dosage. The level of pain after core needle biopsy was evaluated for each patient at 1, 6, 12, 24, 48, and >48 hours by a Visual Analog Scale (VAS). The mean VAS changes over time were compared between the Ketorolac plus Lidocaine and Lidocaine groups using a linear mixed model.Results:baseline information including mean age of patients in Lidocaine group (51.5 ± 19.4 years) and in Lidocaine – Ketorolac combination group (50.1 ± 18 years), diagnosis (malignant, benign, metastatic, infection), tumor location (upper and lower extremities, back), VAS score 1-hour post-operation (mild and moderate pain) were noted. The VAS score ratings were significantly lower in Lidocaine – Ketorolac combination group when compared to the Lidocaine group during the 1 to 24 hours post-operation time period.Conclusion:Patients receiving Lidocaine – Ketorolac combination dosage had significantly lower VAS scores, and these results confirm that local injection of Lidocaine – Ketorolac combination had a superior pain-controlling effect during the first 24 hours after the biopsy procedure in comparison to Lidocaine injection alone, as measured by VAS score scale.     

Z形皮瓣及推进皮瓣修复眼睑缺损的作用探讨

目的探讨眼睑恶性肿瘤切除术中应用Z形皮瓣及推进皮瓣I期修复眼睑缺损的临床效果。方法将50例眼睑恶性肿瘤切除术患者按不同缝合方法分为两组,即对照组25例,术中直接缝合;观察组25例,术中行Z形皮瓣及推进皮瓣I期修复;比较两组眼睑修复效果。结果观察组术后皮瓣成活率96.0%、切口Ⅰ期愈合率100%、修复满意率92.0%,均高于对照组的72.0%、68.0%、56.0%,差异有统计学意义(P<0.05)。观察组术后并发症发生率低于对照组,但差异无统计学意义(P>0.05)。结论眼睑恶性肿瘤切除术中眼睑缺损修复时,采用Z形皮瓣及推进皮瓣,眼睑修复良好,患者修复满意率高,值得推广应用。     

How good is the evidence that cellular senescence causes skin ageing?

Skin is the largest organ of the body with important protective functions, which become compromised with time due to both intrinsic and extrinsic ageing processes. Cellular senescence is the primary ageing process at cell level, associated with loss of proliferative capacity, mitochondrial dysfunction and significantly altered patterns of expression and secretion of bioactive molecules. Intervention experiments have proven cell senescence as a relevant cause of ageing in many organs. In case of skin, accumulation of senescence in all major compartments with ageing is well documented and might be responsible for most, if not all, the molecular changes observed during ageing. Incorporation of senescent cells into in-vitro skin models (specifically 3D full thickness models) recapitulates changes typically associated with skin ageing. However, crucial evidence is still missing. A beneficial effect of senescent cell ablation on skin ageing has so far only been shown following rather unspecific interventions or in transgenic mouse models. We conclude that evidence for cellular senescence as a relevant cause of intrinsic skin ageing is highly suggestive but not yet completely conclusive.     

Characterization of inflammatory changes in the breast cancer associated adipose tissue and comparison to the unaffected contralateral breast

BackgroundAdipose tissue has emerged as an important window into cancer pathophysiology, revealing potential targets for novel therapeutic interventions. The goal of this study was to compare the breast adipose tissue (BrAT) immune milieu surrounding breast carcinoma and contralateral unaffected breast tissue obtained from the same patient.Materials and methodsPatients undergoing bilateral mastectomy for unilateral breast cancer were enrolled for bilateral BrAT collection at the time of operation. After BrAT was processed, adipocyte and stromal vascular fraction (SVF) gene expression was quantified by PCR. SVF cells were also processed for flow cytometric immune cell characterization.ResultsTwelve patients underwent bilateral mastectomy for unilateral ductal carcinoma. BrAT adipocyte CXCL2 gene expression trended higher in the tumor-affected breast as compared to the unaffected breast. Macrophage MCP-1 and PPARγ gene expression also tended to be higher in the tumor-affected breasts. T cell gene expression of FOXP3 (p = 0.0370) were significantly greater in tumor-affected breasts than unaffected breasts. Affected BrAT contained higher numbers of Th2 CD4⁺ cells (p = 0.0165) and eosinophils (p = 0.0095) while trending towards increased macrophage and lower Th1 CD4⁺ cells infiltration than tumor-affected BrAT.ConclusionThis preliminary study aimed to identify the immunologic environment present within BrAT and is the first to directly compare this in individual patients’ tumor-associated and unaffected BrAT. These findings suggest that cancer-affected BrAT had increased levels of T cell specific FOXP3 and higher levels of anti-inflammatory/regulatory cells compared to the contralateral BrAT.     

Cancer Cell-Specific Major Histocompatibility Complex II Expression as a Determinant of the Immune Infiltrate Organization and Function in the NSCLC Tumor Microenvironment

IntroductionIn patients with NSCLC, the prognostic significance of the tumor microenvironment (TME) immune composition has been revealed using single- or dual-marker staining on sequential tissue sections. Although these studies reveal that relative abundance and localization of immune cells are important parameters, deeper analyses of the NSCLC TME are necessary to refine the potential application of these findings to clinical care. Currently, the complex spatial relationships between cells of the NSCLC TME and potential drivers contributing to its immunologic composition remain unknown.MethodsWe used multispectral quantitative imaging on the lung adenocarcinoma TME in 153 patients with resected tumors. On a single slide per patient, we evaluated the TME with markers for CD3, CD8, CD14, CD19, major histocompatibility complex II (MHCII), cytokeratin, and 4′,6-diamidino-2-phenylindole (DAPI). Image analysis, including tissue segmentation, phenotyping, and spatial localization, was performed.ResultsSpecimens wherein greater than or equal to 5% of lung cancer cells expressed MHCII (MHCII^hi TME) had increased levels of CD4⁺ and CD8⁺ T cells and CD14⁺ cell infiltration. In the MHCII^hi TME, the immune infiltrate was closer to cancer cells and expressed an activated phenotype. Morphologic image analysis revealed cancer cells in the MHCII^hi TME more frequently interfaced with CD4⁺ and CD8⁺ T cells. Patients with an MHCII^hi TME experienced improved overall survival (p = 0.046).ConclusionsLung cancer cell-specific expression of MHCII associates with levels of immune cell infiltration, spatial localization, and activation status within the TME. This suggests that cancer cell-specific expression of MHCII may represent a biomarker for the immune system’s recognition and activation against the tumor.     

Comparison of the treatment results of knee osteoarthritis using adipose tissue mesenchymal stromal cells derived through enzymatic digestion and mechanically fragmented adipose tissue

Introduction:Knee osteoarthritis is a common condition that affects daily functioning and decreases the quality of life. There are many ways of treatment depending on the stage of the disease. Advanced cases are qualified for arthroplasty, which is an extensive and demanding surgical procedure. Less advanced stages are treated in various ways: from rehabilitation, through oral and intra-articular pharmacotherapy, to surgical treatment (arthroscopy, osteotomy). Because surgical treatment is risky, scientists focus on less invasive therapeutic methods. The most valuable management is based on regeneration. Mesenchymal stromal cells (MSC) derived from the adipose tissue have a great regenerative and anti-inflammatory potential, therefore an attempt is being made to take advantage of them in knee osteoarthritis treatment.The study aims to compare the clinical effects of treatment of knee osteoarthritis using adipose tissue MSC obtained by an enzymatic method with the outcomes of the therapy with the mechanically fragmented adipose tissue.Methods:One hundred adults with primary knee osteoarthritis will undergo lipoaspiration under sterile conditions. The collected lipoaspirates will be further processed, depending on the randomly assigned group-enzymatically with the use of collagenase or mechanically using the Lipogems system. The preparations will be administered to the patients’ knee joints in the operating room under ultrasound control.The results of treatment will be assessed using Knee Injury and Osteoarthritis Outcome Score, measuring the flexibility of the knee joint, evaluating joint gap in X-ray and the quality of cartilage in magnetic resonance T2-mapping during 1 year after treatment.Discussion/conclusion:Identification and functional analysis of the regenerative capacity of adipose-derived MSC depending on three variables (body weight, sex, and age) will help to develop a targeted therapy for different groups of patients and will determine the effectiveness of both methods of treatment. An attempt will be made to identify groups of patients with the greatest regenerative potential of the adipose tissue, and thus indicate those with the most probable improvement of the joint condition.Trial registration:This study protocol has been approved by the Ethics Committee of Medical University of Warsaw and registered on www.clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT04675359","term_id":"NCT04675359"}}NCT04675359 (06 Jan 2021)