Local Treatment of Burns with Cell-Based Therapies Tested in Clinical Studies

Effective wound management is an important determinant of the survival and prognosis of patients with severe burns. Thus, novel techniques for timely and full closure of full-thickness burn wounds are urgently needed. The purpose of this review is to present the current state of knowledge on the local treatment of burn wounds (distinguishing radiation injury from other types of burns) with the application of cellular therapies conducted in clinical studies. PubMed search engine and ClinicalTrials.gov were used to analyze the available data. The analysis covered 49 articles, assessing the use of keratinocytes (30), keratinocytes and fibroblasts (6), fibroblasts (2), bone marrow-derived cells (8), and adipose tissue cells (3). Studies on the cell-based products that are commercially available (Epicel®, Keraheal™, ReCell®, JACE, Biobrane®) were also included, with the majority of reports found on autologous and allogeneic keratinocytes. Promising data demonstrate the effectiveness of various cell-based therapies; however, there are still scientific and technical issues that need to be solved before cell therapies become standard of care. Further evidence is required to demonstrate the clinical efficacy and safety of cell-based therapies in burns. In particular, comparative studies with long-term follow-up are critical.

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The evolution of alternative splicing in glioblastoma under therapy

Genome Biology ◽

10.1186/s13059-021-02259-5 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Lin Wang ◽

Karin Shamardani ◽

Husam Babikir ◽

Francisca Catalan ◽

Takahide Nejo ◽

...

Keyword(s):

Alternative Splicing ◽

Standard Of Care ◽

Surface Proteins ◽

Adult Brain ◽

Primary Tumors ◽

Cell Therapies ◽

Therapeutic Development ◽

Human Gbm ◽

Tissue Specimens ◽

Splicing Patterns

Abstract Background Alternative splicing is a rich source of tumor-specific neoantigen targets for immunotherapy. This holds promise for glioblastomas (GBMs), the most common primary tumors of the adult brain, which are resistant to standard-of-care therapy. Although most clinical trials enroll patients at recurrence, most preclinical studies have been done with specimens from primary disease. There are limited expression data from GBMs at recurrence and surprisingly little is known about the evolution of splicing patterns under therapy. Result We profile 37 primary-recurrent paired human GBM specimens via RNA sequencing. We describe the landscape of alternative splicing in GBM at recurrence and contrast that to primary and non-malignant brain-tissue specimens. By screening single-cell atlases, we identify cell-type-specific splicing patterns and novel splicing events in cell-surface proteins that are suitable targets for engineered T cell therapies. We identify recurrent-specific isoforms of mitogen-activated kinase pathway genes that enhance invasiveness and are preferentially expressed by stem-like cells. Conclusion These studies shed light on gene expression in recurrent GBM and identify novel targets for therapeutic development.

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Cell therapy for lung disease

European Respiratory Review ◽

10.1183/16000617.0044-2017 ◽

2017 ◽

Vol 26 (144) ◽

pp. 170044 ◽

Cited By ~ 33

Author(s):

Sabine Geiger ◽

Daniela Hirsch ◽

Felix G. Hermann

Keyword(s):

Clinical Studies ◽

Therapeutic Approach ◽

Lung Diseases ◽

Distress Syndrome ◽

Treatment Options ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Cell Therapies ◽

Promising Therapeutic Approach ◽

Preclinical And Clinical Studies

Besides cancer and cardiovascular diseases, lung disorders are a leading cause of morbidity and death worldwide. For many disease conditions no effective and curative treatment options are available. Cell therapies offer a novel therapeutic approach due to their inherent anti-inflammatory and anti-fibrotic properties. Mesenchymal stem/stromal cells (MSC) are the most studied cell product. Numerous preclinical studies demonstrate an improvement of disease-associated parameters after MSC administration in several lung disorders, including chronic obstructive pulmonary disease, acute respiratory distress syndrome and idiopathic pulmonary fibrosis. Furthermore, results from clinical studies using MSCs for the treatment of various lung diseases indicate that MSC treatment in these patients is safe. In this review we summarise the results of preclinical and clinical studies that indicate that MSCs are a promising therapeutic approach for the treatment of lung diseases. Nevertheless, further investigations are required.

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Intracardiac Self Insertion of a Darning Needle in a Psychiatric Patient

Clinical Cardiology and Cardiovascular Interventions ◽

10.31579/2641-0419/127 ◽

2021 ◽

Vol 4 (5) ◽

pp. 01-13

Author(s):

Avra Laarakker

Keyword(s):

Left Ventricle ◽

Psychiatric Patient ◽

Surgical Intervention ◽

Case Reports ◽

Interventricular Septum ◽

Intravenous Drug User ◽

Standard Of Care ◽

Pubmed Search ◽

Needle Entry ◽

The Right

Objective: We report a case of self inserted needle into the left ventricle of the heart and a description of our surgical intervention in a psychiatric patient without decision-making capacity. We discuss issues regarding obtaining consent in this patient with a sub-acute presentation, report our operative approach, and summarize a treatment approach based on a review of current literature. Methods: A PubMed search using terms “needle, “heart”, “insertion”, “intracardiac foreign object”, yielded 69 relevant papers. 67 of these were case reports yielding 72 individual cases. Age, gender, cause of the needle entry (Accidental Plus (A+), Intravenous Drug User [IVDU], Self-inflicted (SI)), type of needle, location in heart, neuropsychiatric history, treatment, and outcome were documented. Results: Within the SI category, there were a total of 28 cases, 89.3% had a neuropsychiatric history whereas only there were only 2 such patients in both the IVDU and A+ group. The location of the needle in the heart in all 72 cases was as follows: right ventricle 40.3%, other 20.8%, left ventricle 19.4 %, ventricle and interventricular septum 16.7% and the right and left atrium were each 1.4 %. In all three groups (n=72), 77.8% of patients underwent surgery, with 92.9% having a stable outcome. Conclusion: Our case and review demonstrates that management of such cases, particularly when active mental health issues are present, requires a case-by-case evaluation and treatment as a specific standard of care has not been established. Surgical intervention appears to be the preferred management regardless of presentation with good outcomes. Running Title: Intracardiac Self Insertion of a Darning Needle in a Psychiatric Patient

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Commercialization of cellular immunotherapies for cancer

Biochemical Society Transactions ◽

10.1042/bst20150240 ◽

2016 ◽

Vol 44 (2) ◽

pp. 329-332 ◽

Cited By ~ 16

Author(s):

Anthony Walker ◽

Robert Johnson

Keyword(s):

Economies Of Scale ◽

Technology Development ◽

Standard Of Care ◽

Production Costs ◽

Capital Investments ◽

Cell Therapies ◽

Antibody Therapeutics ◽

Commercial Viability ◽

A Cell ◽

Very High

Successful commercialization of a cell therapy requires more than proving safety and efficacy to the regulators. The inherent complexity of cellular products delivers particular manufacturing, logistical and reimbursement hurdles that threaten commercial viability for any therapy with a less than spectacular clinical profile that truly changes the standard of care. This is particularly acute for autologous cell therapies where patients receive bespoke treatments manufactured from a sample of their own cells and where economies of scale, which play an important role in containing the production costs for small molecule and antibody therapeutics, are highly limited. Nevertheless, the promise of ‘game-changing’ efficacy, as exemplified by very high levels of complete responses in refractory haematological malignancies, has attracted capital investments on a vast scale, and the attendant pace of technology development provides promising indicators for future clinical and commercial success.

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Case Report: Rechallenge With BRAF and MEK Inhibitors in Metastatic Melanoma: A Further Therapeutic Option in Salvage Setting?

Frontiers in Oncology ◽

10.3389/fonc.2021.645008 ◽

2021 ◽

Vol 11 ◽

Author(s):

Anna Stagno ◽

Sabrina Vari ◽

Alessio Annovazzi ◽

Vincenzo Anelli ◽

Michelangelo Russillo ◽

...

Keyword(s):

Targeted Therapy ◽

Clinical Benefit ◽

Kinase Inhibitors ◽

Checkpoint Inhibitors ◽

Therapeutic Option ◽

Local Treatment ◽

Standard Of Care ◽

Serum Levels ◽

High Serum ◽

Mek Inhibitors

BackgroundThe combination of BRAF and MEK inhibitors represents the standard of care treatment for patients with metastatic BRAF-mutated melanoma, notwithstanding the high frequency of emergent resistance. Moreover, therapeutic options outside clinical trials are scarce when patients have progressed after both targeted therapy and therapy with immune checkpoint inhibitors. In this article, we report our experience with targeted therapy rechallenging with BRAF and MEK inhibitors in patients with metastatic BRAF-mutated melanoma after progression with kinase inhibitors and immunotherapy.MethodsFour patients with metastatic BRAF-mutated melanoma were rechallenged with BRAF and MEK inhibitors after progression with targeted therapy and subsequent immunotherapy (checkpoint inhibitors).ResultsTwo patients (one of them was heavily pretreated) had partial response over 36 months (with local treatment on oligoprogression disease) and 10 months, respectively. A third patient with multisite visceral disease and high serum levels of lactate dehydrogenase had a short-lived clinical benefit rapidly followed by massive progression of disease (early progressor). The fourth patient, currently on treatment with BRAF/MEK inhibitors, is showing a clinical benefit and radiological stable disease over 3 months of therapy. Adverse events were manageable, similar to those reported during the first targeted therapy; the treatment was better tolerated at rechallenge compared with the first treatment by two out of four patients.

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Consolidative radiotherapy for metastatic urothelial bladder cancer patients without progression and with no more than three residual metastatic lesions following first line systemic therapy: A prospective randomized comparative phase II trial (BLAD RAD01/GETUG-AFU V07).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.tps4588 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. TPS4588-TPS4588

Author(s):

Jonathan Khalifa ◽

Damien Pouessel ◽

Mathieu Roumiguie ◽

Paul Sargos ◽

Genevieve Loos ◽

...

Keyword(s):

Phase Ii ◽

Systemic Therapy ◽

Phase Ii Trial ◽

Local Treatment ◽

Standard Of Care ◽

Urothelial Bladder Cancer ◽

First Line ◽

Metastatic Lesions ◽

Urothelial Bladder ◽

Consolidative Radiotherapy

TPS4588 Background: Consolidative local treatment of the primary tumor in the treatment of metastatic malignancies has shown promising results in several types of tumors, mostly relying on the seed-and-soil theory. Furthermore, the local treatment of the residual metastases following systemic treatment is a promising approach, in part due to the high incidence of progression at prior sites of disease in patients who had initially responded to chemotherapy. To date, no prospective data exists on such consolidative approach in metastatic urothelial bladder cancer (mUBC). The phase II trial BLAD-RAD01 GETUG-AFU V07 was designed to investigate the role of local consolidative radiotherapy in patients with limited mUBC and without progression following the initial phase of first-line systemic therapy. Methods: This is a phase II, multicenter, randomized open-label and comparative study. Patients with mUBC (excluding brain and liver metastases), without progression following standard first-line systemic therapy according to RECIST v1.1, and with no more than 3 residual metastatic lesions on 18FDG-PET scanner and/or contrast-enhanced CT-scanner are eligible for the study. After the completion of systemic treatment, an estimated 130 patients will be randomized in a 1:1 ratio between consolidative local treatment (pelvic radiotherapy +/- previous transurethal resection of bladder tumor, associated with stereotactic body radiotherapy (SBRT) to the residual metastases) plus standard of care (arm B) and standard of care only (arm A). Stratification is performed based upon: the center, the ECOG performance status, the administration of immunotherapy or not, the number of residual metastatic lesions and the imaging modality for assessment of the number of residual lesions. To date, standard of care for this population is maintenance treatment with avelumab. Radiotherapy regimens consist in conventionally fractionated (64Gy in 32 fractions) or hypofractionated (55Gy in 20 fractions) irradiation of the bladder, optional pelvic nodes irradiation, and 3 to 5 fractions of 6 to 18 Gy in SBRT for metastases, depending on the location. The main objective is to detect an increase in 20-month overall survival rate following chemotherapy from 50% (based upon the JAVELIN 100 trial) to 66%; this corresponds to a hazard ratio of 0.6. A total of 83 events are necessary for 85% power to detect this difference if it is true using a one-sided logrank test at the 10% of significance. Target difference, type I and II error rates are relaxed and compatibles with recommendations for comparative phase II trials. Key secondary endpoints are progression free survival, safety and quality of life. To date, one patient has been enrolled and eight centers are open for accrual. Clinical trial information: NCT04428554.

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Primary Wound Management: Strategy Concerning Local Treatment

Color Atlas of Burn Reconstructive Surgery ◽

10.1007/978-3-642-05070-1_2 ◽

2010 ◽

pp. 6-9

Author(s):

Luc Téot

Keyword(s):

Management Strategy ◽

Local Treatment ◽

Wound Management

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Systematic Review of Stem-Cell-Based Therapy of Burn Wounds: Lessons Learned from Animal and Clinical Studies

Cells ◽

10.3390/cells9122545 ◽

2020 ◽

Vol 9 (12) ◽

pp. 2545

Author(s):

Josefine Lin Henriksen ◽

Nana Brandborg Sørensen ◽

Trine Fink ◽

Vladimir Zachar ◽

Simone Riis Porsborg

Keyword(s):

Wound Healing ◽

Systematic Reviews ◽

Clinical Studies ◽

Meta Analysis ◽

Lessons Learned ◽

Burn Patients ◽

Thermal Burn ◽

Burn Wounds ◽

Cell Based Therapy ◽

Healing Phase

Treatment of severe burn wounds presents a daunting medical challenge, and novel approaches promoting healing and reducing scarring are highly desirable. The application of mesenchymal stem/stromal cells (MSCs) has been suggested as a novel treatment. In this paper, we present systematic reviews of pre-clinical and clinical studies of MSC therapy for second- or third-degree thermal burn wounds. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, the PubMed and Embase databases were searched, and interventional studies of MSC therapy using rodent models (21 studies) or human burn patients (three studies) were included in the pre-clinical and clinical reviews, respectively, where both overall outcome and wound-healing-phase-specific methodologies and effects were assessed. The pre-clinical studies demonstrated a promising effect of the application of MSCs on several wound healing phases. The clinical studies also suggested that the MSC treatment was beneficial, particularly in the remodeling phase. However, the limited number of studies, their lack of homogeneity in study design, relatively high risk of bias, lack of reporting on mode of action (MOA), and discontinuity of evidence restrict the strength of these findings. This comprehensive review presents an overview of available methodologies to assess the MOA of MSC treatment for distinct wound healing phases. Furthermore, it includes a set of recommendations for the design of high-quality clinical studies that can determine the efficacy of MSCs as a therapy for burn wounds.

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Efficacy of Using Probiotics with Antagonistic Activity against Pathogens of Wound Infections: An Integrative Review of Literature

BioMed Research International ◽

10.1155/2019/7585486 ◽

2019 ◽

Vol 2019 ◽

pp. 1-21 ◽

Cited By ~ 6

Author(s):

Sabina Fijan ◽

Anita Frauwallner ◽

Tomaž Langerholc ◽

Bojan Krebs ◽

Jessica A. ter Haar (née Younes) ◽

...

Keyword(s):

Clinical Studies ◽

Animal Studies ◽

Lactobacillus Rhamnosus ◽

Foot Ulcer ◽

Surgical Site Infections ◽

Integrative Review ◽

Wound Management ◽

Wound Infections ◽

Skin Damage

The skin and its microbiota serve as physical barriers to prevent invasion of pathogens. Skin damage can be a consequence of illness, surgery, and burns. The most effective wound management strategy is to prevent infections, promote healing, and prevent excess scarring. It is well established that probiotics can aid in skin healing by stimulating the production of immune cells, and they also exhibit antagonistic effects against pathogens via competitive exclusion of pathogens. Our aim was to conduct a review of recent literature on the efficacy of using probiotics against pathogens that cause wound infections. In this integrative review, we searched through the literature published in the international following databases: PubMed, ScienceDirect, Web of Science, and Scopus using the search terms “probiotic” AND “wound infection.” During a comprehensive review and critique of the selected research, fourteen in vitro studies, 8 animal studies, and 19 clinical studies were found. Two of these in vitro studies also included animal studies, yielding a total of 39 articles for inclusion in the review. The most commonly used probiotics for all studies were well-known strains of the species Lactobacillus plantarum, Lactobacillus casei, Lactobacillus acidophilus, and Lactobacillus rhamnosus. All in vitro studies showed successful inhibition of chosen skin or wound pathogens by the selected probiotics. Within the animal studies on mice, rats, and rabbits, probiotics showed strong opportunities for counteracting wound infections. Most clinical studies showed slight or statistically significant lower incidence of surgical site infections, foot ulcer infection, or burn infections for patients using probiotics. Several of these studies also indicated a statistically significant wound healing effect for the probiotic groups. This review indicates that exogenous and oral application of probiotics has shown reduction in wound infections, especially when used as an adjuvant to antibiotic therapy, and therefore the potential use of probiotics in this field remains worthy of further studies, perhaps focused more on typical skin inhabitants as next-generation probiotics with high potential.

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