Wound healing complications with lenvatinib identified in a pharmacovigilance database

2018 ◽  
Vol 25 (8) ◽  
pp. 1817-1822 ◽  
Author(s):  
Connie Cheng ◽  
Afrouz Nayernama ◽  
S Christopher Jones ◽  
Denise Casey ◽  
Peter E Waldron
Keyword(s):  
Wound Healing ◽  
Kinase Inhibitors ◽  
Tissue Injury ◽  
Risk Mitigation ◽  
Adverse Event Reporting System ◽  
Case Series ◽  
Wound Dehiscence ◽  
Safety Risk ◽  
Impaired Healing ◽  
Wide Range

The U.S. Food and Drug Administration (FDA) has approved several vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors, including lenvatinib, for thyroid and renal malignancies. Inhibition of the VEGFR signaling pathway impairs angiogenesis and can disrupt wound healing. The objective of this work was to evaluate wound healing complications as a potential safety risk for patients treated with lenvatinib. We searched the FDA Adverse Event Reporting System (FAERS) database for postmarketing reports of wound healing complications with lenvatinib between 13 February 2015 (FDA approval date) and 15 February 2017. The search identified nine FAERS cases of lenvatinib-associated wound healing complications that were not previously reported in the medical literature. Seven cases involved postoperative wound healing complications, such as impaired healing or wound dehiscence. In our case series, the reported time to identification of delayed wound healing from tissue injury or surgery varied over a wide range (4–58 days). The time of initial lenvatinib exposure relative to the tissue injury was also highly varied in our series, which may have influenced the development and detection of impaired healing. FAERS case-level evidence suggests that lenvatinib may have contributed to wound healing complications based on temporality and biologic plausibility. Healthcare professionals should be aware of this safety risk to facilitate prompt recognition and risk mitigation.

scholarly journals AB0421 MANAGEMENT OF ULCERATION IN SYSTEMIC SCLEROSIS BY A SPECIALIST PODIATRY SERVICE; A CASE SERIES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1239.1-1239
Author(s):  
L. Parker ◽  
R. Field ◽  
J. Marks
Keyword(s):  
Wound Healing ◽  
Systemic Sclerosis ◽  
Tissue Injury ◽  
Wound Care ◽  
Case Series ◽  
Low Level Laser Therapy ◽  
Diffuse Fibrosis ◽  
Contributory Factor ◽  
Digital Ulcers ◽  
Targeting Therapy

Background:Systemic sclerosis is a chronic disorder characterised by diffuse fibrosis and vascular abnormalities in the skin and major organs. Digital ulceration is a common complication, often resulting in patient disability. These ulcers can form through a variety of processes and management should be tailored according to aetiology. In Dorset, the specialist podiatry service has created a unique facility for optimal wound care in the setting of digital ulceration.Objectives:In this case series, we outline podiatric management of 4 common causes of digital ulceration in systemic sclerosis.Methods:Tissue ischaemia, infection, micro-trauma and calcinosis were identified as four major contributory factors resulting in ulceration or delayed wound healing. Four cases exemplifying management of each different contributory factor were identified and their case notes reviewed in order to extract clinically relevant data and images.Results:Case 1 illustrates treatment of ischaemic tissue injury to promote earlier healing, using careful wound care, debridement under local anaesthetic and low-level laser therapy.Case 2 illustrates the importance of identifying repeated micro-trauma as a contributing factor to non-healing ulceration.Case 3 demonstrates how surgical debridement or removal of the subcutaneous calcinosis in an outpatient setting can be a useful adjunct in encouraging ulcer healing.Case 4 illustrates the complexity of correctly identifying infection in the setting of ulceration, with prompt management promoting wound healing.Conclusion:The pathophysiology of ischaemic tissue damage in scleroderma is complex and can reflect a broad range of vascular pathologies, often occurring concurrently1 including vasospasm, macrovascular disease and microvascular vasculopathy, leading to digital ulceration. Rapid identification of which processes are driving the ischaemia is critical in targeting therapy to the affected individual. A local podiatry service with expertise in management of tissue -related complications of systemic sclerosis is invaluable in promoting wound healing and preventing further complications.References:[1]Hughes M, Herrick A L. Digital ulcers in systemic sclerosis. Rheumatology 2017; 56(1):14-25.Disclosure of Interests:None declared

BRAFV600E MUTATION IN PAPILLARY THYROID CARCINOMA. CLINICAL AND METHODOLOGICAL ASPECTS

2019 ◽  
Vol 65 (1) ◽  
pp. 16-26
Author(s):  
Pavel Rumyantsev ◽  
Petr Nikiforovich ◽  
Andrey Poloznikov ◽  
Andrey Abrosimov ◽  
Vladimir Saenko ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Kinase Inhibitors ◽  
Anaplastic Carcinoma ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Wide Range ◽  
Methodological Aspects

Mutation BRAFV600E is highly specific for papillary thyroid carcinoma. It’s detected in 40-70% of all papillary thyroid carcinoma cases. Moreover this mutation is noticed in anaplastic carcinoma in 40-50%.This fact gives a chance to select patients and provide targeted therapy with multi-kinase inhibitors in cases of unresectable anaplastic carcinoma. The influence of BRAF V600E mutation for response to radioactive iodine therapy requires more evidence-based research. Existing methods for determining the BRAFV600E mutation have different accuracy, availability and cost. Other methodological aspects are also associated with the sample preparation of biological material, the quality of reagents, and the cross-validation of research results. In this review, on the basis of our own experience and literature data, the indications for determining the mutation of the BRAFV600E gene in clinical practice are refined, and a comprehensive comparative analysis of modern research methods has been conducted. This review is focused on a wide range of specialists of different types: oncologists, endocrinologists, radiologists, pathologists, and biologists.

Approach in improving potency and selectivity of kinase inhibitors: Allosteric kinase inhibitors

2020 ◽  
Vol 21 ◽  
Author(s):  
Shangfei Wei ◽  
Tianming Zhao ◽  
Jie Wang ◽  
Xin Zhai
Keyword(s):  
Protein Interactions ◽  
Kinase Inhibitors ◽  
Binding Modes ◽  
Allosteric Inhibitors ◽  
Wide Range ◽  
Allosteric Sites ◽  
Protein Functions ◽  
Regulate Protein

: Allostery is an efficient and particular regulatory mechanism to regulate protein functions. Different from conserved orthosteric sites, allosteric sites have distinctive functional mechanism to form the complex regulatory network. In drug discovery, kinase inhibitors targeting the allosteric pockets have received extensive attention for the advantages of high selectivity and low toxicity. The approval of trametinib as the first allosteric inhibitor validated that allosteric inhibitors could be used as effective therapeutic drugs for treatment of diseases. To date, a wide range of allosteric inhibitors have been identified. In this perspective, we outline different binding modes and potential advantages of allosteric inhibitors. In the meantime, the research processes of typical and novel allosteric inhibitors are described briefly in terms of structureactivity relationships, ligand-protein interactions and in vitro and in vivo activity. Additionally, challenges as well as opportunities are presented.

Healing effects of curcumin nanoparticles in deep tissue injury mouse model.

2020 ◽  
Vol 18 ◽  
Author(s):  
Zirui Zhang ◽  
Shangcong Han ◽  
Panpan Liu ◽  
Xu Yang ◽  
Jing Han ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mrna Expression ◽  
Tissue Injury ◽  
Inflammatory Cells ◽  
Pcr Analysis ◽  
Protective Effects ◽  
Deep Tissue ◽  
Deep Tissue Injury

Background: Chronic inflammation and lack of angiogenesis are the important pathological mechanisms in deep tissue injury (DTI). Curcumin is a well-known anti-inflammatory and antioxidant agent. However, curcumin is unstable under acidic and alkaline conditions, and can be rapidly metabolized and excreted in the bile, which shortens its bioactivity and efficacy. Objective: This study aimed to prepare curcumin-loaded poly (lactic-co-glycolic acid) nanoparticles (CPNPs) and to elucidate the protective effects and underlying mechanisms of wound healing in DTI models. Methods: CPNPs were evaluated for particle size, biocompatibility, in vitro drug release and their effect on in vivo wound healing. Results : The results of in vivo wound closure analysis revealed that CPNP treatments significantly improved wound contraction rates (p<0.01) at a faster rate than other three treatment groups. H&E staining revealed that CPNP treatments resulted in complete epithelialization and thick granulation tissue formation, whereas control groups resulted in a lack of compact epithelialization and persistence of inflammatory cells within the wound sites. Quantitative real-time PCR analysis showed that treatment with CPNPs suppressed IL-6 and TNF-α mRNA expression, and up-regulated TGF-β, VEGF-A and IL-10 mRNA expression. Western blot analysis showed up-regulated protein expression of TGF-β, VEGF-A and phosphorylatedSTAT3. Conclusion: Our results showed that CPNPs enhanced wound healing in DTI models, through modulation of the JAK2/STAT3 signalling pathway and subsequent upregulation of pro-healing factors.

Isoform-Selective PI3K Inhibitors for Various Diseases

2020 ◽  
Vol 20 (12) ◽  
pp. 1074-1092 ◽  
Author(s):  
Rammohan R.Y. Bheemanaboina
Keyword(s):  
Intracellular Signaling ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Type I ◽  
Selective Inhibitors ◽  
Pi3k Inhibitors ◽  
Wide Range ◽  
Lipid Kinases ◽  
Isoform Selectivity

Phosphoinositide 3-kinases (PI3Ks) are a family of ubiquitously distributed lipid kinases that control a wide variety of intracellular signaling pathways. Over the years, PI3K has emerged as an attractive target for the development of novel pharmaceuticals to treat cancer and various other diseases. In the last five years, four of the PI3K inhibitors viz. Idelalisib, Copanlisib, Duvelisib, and Alpelisib were approved by the FDA for the treatment of different types of cancer and several other PI3K inhibitors are currently under active clinical development. So far clinical candidates are non-selective kinase inhibitors with various off-target liabilities due to cross-reactivities. Hence, there is a need for the discovery of isoform-selective inhibitors with improved efficacy and fewer side-effects. The development of isoform-selective inhibitors is essential to reveal the unique functions of each isoform and its corresponding therapeutic potential. Although the clinical effect and relative benefit of pan and isoformselective inhibition will ultimately be determined, with the development of drug resistance and the demand for next-generation inhibitors, it will continue to be of great significance to understand the potential mechanism of isoform-selectivity. Because of the important role of type I PI3K family members in various pathophysiological processes, isoform-selective PI3K inhibitors may ultimately have considerable efficacy in a wide range of human diseases. This review summarizes the progress of isoformselective PI3K inhibitors in preclinical and early clinical studies for anticancer and other various diseases.

scholarly journals Use of an advanced collagen matrix dressing on patients with complex chronic lower extremity ulcers: A case series

2021 ◽  
Vol 9 ◽  
pp. 2050313X2110136
Author(s):  
Afsaneh Alavi ◽  
Jeannine Archer ◽  
Patricia Coutts
Keyword(s):  
Wound Healing ◽  
Lower Extremity ◽  
Ethylenediaminetetraacetic Acid ◽  
Case Series ◽  
Standard Of Care ◽  
Collagen Matrix ◽  
Contact Layer ◽  
Complete Healing ◽  
Average Decrease

The objective of this case series was to assess the wound healing effectiveness of a collagen matrix wound dressing containing partially denatured collagen, carboxymethyl cellulose, alginate and ethylenediaminetetraacetic acid in chronic lower extremity ulcers. A total of nine patients with refractory lower extremity ulcers were treated with the collagen contact layer in addition to standard of care. Wound healing progress was measured at 2, 4 and 8 weeks. An average decrease in wound size of 73% was achieved across patients at week 8, with complete healing in two patients. The intervention was easy to use and well tolerated by patients. The results of this study, although preliminary, suggest that the advanced collagen matrix dressing represents an effective and safe treatment strategy for healing refractory chronic lower extremity ulcers of varying etiologies. Further investigation is needed to evaluate efficacy in a larger randomized clinical trial with focus on cost-effectiveness and impact on patient’s quality-of-life.

Punch Grafting for the Management of Hard-to-Heal Diabetic Foot Ulcers: A Prospective Case Series

2021 ◽  
pp. 153473462110310
Author(s):  
Marta García-Madrid ◽  
Irene Sanz-Corbalán ◽  
Aroa Tardáguila-García ◽  
Raúl J. Molines-Barroso ◽  
Mateo López-Moral ◽  
...  
Keyword(s):  
Wound Healing ◽  
Clinical Outcomes ◽  
Diabetic Foot ◽  
Donor Site ◽  
Case Series ◽  
Foot Ulcers ◽  
Diabetic Foot Ulcers ◽  
Wound Debridement ◽  
Prospective Case Series

Punch grafting is an alternative treatment to enhance wound healing which has been associated with promising clinical outcomes in various leg and foot wound types. We aimed to evaluate the clinical outcomes of punch grafting as a treatment for hard-to-heal diabetic foot ulcers (DFUs). Six patients with chronic neuropathic or neuroischemic DFUs with more than 6 months of evolution not responding to conventional treatment were included in a prospective case series between May 2017 and December 2020. All patients were previously debrided using an ultrasound-assisted wound debridement and then, grafted with 4 to 6 mm punch from the donor site that was in all cases the anterolateral aspect of the thigh. All patients were followed up weekly until wound healing. Four (66.7%) DFUs were located in the heel, 1 (16.7%) in the dorsal aspect of the foot and 1 (16.7%) in the Achilles tendon. The median evolution time was 172 (interquartile range [IQR], 25th-75th; 44-276) weeks with a median area of 5.9 (IQR; 1.87-37.12) cm2 before grafting. Complete epithelization was achieved in 3 (50%) patients at 12 weeks follow-up period with a mean time of 5.67 ± 2.88 weeks. Two of the remaining patients achieved wound healing at 32 and 24 weeks, respectively, and 1 patient showed punch graft unsuccessful in adhering. The median time of wound healing of all patients included in the study was 9.00 (IQR; 4.00-28.00) weeks. The wound area reduction (WAR) at 4 weeks was 38.66% and WAR at 12 weeks was 88.56%. No adverse effects related to the ulcer were registered through the follow-up period. Autologous punch graft is an easy procedure that promotes healing, achieving wound closure in chronic DFUs representing an alternative of treatment for hard-to-heal DFUs in which conservative treatment has been unsuccessful.

scholarly journals Medical-Grade Honey as an Alternative Treatment for Antibiotics in Non-Healing Wounds—A Prospective Case Series

Antibiotics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 918
Author(s):  
Adéla Holubová ◽  
Lucie Chlupáčová ◽  
Lada Cetlová ◽  
Niels A. J. Cremers ◽  
Andrea Pokorná
Keyword(s):  
Antibiotic Treatment ◽  
Healing Process ◽  
Case Series ◽  
Wound Dehiscence ◽  
Surgical Wound Dehiscence ◽  
Infected Wounds ◽  
Healing Wounds ◽  
Anti Inflammatory ◽  
Prospective Case Series ◽  
Medical Grade

Non-healing wounds are usually colonised by various types of bacteria. An alternative to antibiotic treatment in patients with infected wounds with local signs of inflammation may be medical-grade honey (MGH), which favourably affects the healing process with its antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory properties. The objective of this study was to evaluate the effect of MGH therapy on the healing process of non-healing wounds of various aetiologies and different wound colonisations. Prospective, observation–intervention case studies (n = 9) of patients with wounds of various aetiologies (venous leg ulcers, diabetic foot ulcers, surgical wound dehiscence) are presented. All wounds were treated with MGH and the healing trajectory was rigorously and objectively monitored. In all cases, pain, odour, and exudation were quickly resolved, which led to an improvement in the quality of life of patients. Despite the proven bacterial microflora in wounds, antibiotic treatment was not necessary. The effects of MGH alleviated the signs of local infection until their complete elimination. In eight out of nine cases, the non-healing wound was completely healed. MGH has antimicrobial, anti-inflammatory, and antioxidant effects in wounds of various aetiologies and forms an effective alternative for the use of antibiotics for treating locally infected wounds.

scholarly journals Cellular effects of glycine and trehalose air-polishing powders on human gingival fibroblasts in vitro

2021 ◽  
Author(s):  
Jens Weusmann ◽  
James Deschner ◽  
Jean-Claude Imber ◽  
Anna Damanaki ◽  
Natalia D. P. Leguizamón ◽  
...  
Keyword(s):  
Wound Healing ◽  
Cell Function ◽  
Nuclear Translocation ◽  
In Vitro Study ◽  
Human Gingival Fibroblasts ◽  
Mrna Levels ◽  
Gingival Fibroblasts ◽  
Air Polishing ◽  
Wide Range

Abstract Objectives Air-polishing has been used in the treatment of periodontitis and gingivitis for years. The introduction of low-abrasive powders has enabled the use of air-polishing devices for subgingival therapy. Within the last decade, a wide range of different low-abrasive powders for subgingival use has been established. In this study, the effects of a glycine powder and a trehalose powder on human gingival fibroblasts (HGF) were investigated. Methods HGF were derived from three systemically and periodontally healthy donors. After 24 h and 48 h of incubation time, mRNA levels, and after 48 h, protein levels of TNFα, IL-8, CCL2, and VEGF were determined. In addition, NF-κB p65 nuclear translocation and in vitro wound healing were assessed. Statistical analysis was performed by ANOVA and post hoc Dunnett’s and Tukey’s tests (p < 0.05). Results Glycine powder significantly increased the expression of proinflammatory genes and showed exploitation of the NF-κB pathway, albeit trehalose powder hardly interfered with cell function and did not trigger the NF-κB pathway. In contrast to trehalose, glycine showed a significant inhibitory effect on the in vitro wound healing rate. Conclusion Subgingivally applicable powders for air-polishing devices can regulate cell viability and proliferation as well as cytokine expression. Our in vitro study suggests that the above powders may influence HGF via direct cell effects. Trehalose appears to be relatively inert compared to glycine powder.

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