Cellular therapeutics and immunotherapies in wound healing - on the pulse of time?

Chronic, non-healing wounds represent a significant challenge for healthcare systems worldwide, often requiring significant human and financial resources. Chronic wounds arise from the complex interplay of underlying comorbidities, such as diabetes or vascular diseases, lifestyle factors, and genetic risk profiles which may predispose extremities to local ischemia. Injuries are further exacerbated by bacterial colonization and the formation of biofilms. Infection, consequently, perpetuates a chronic inflammatory microenvironment, preventing the progression and completion of normal wound healing. The current standard of care (SOC) for chronic wounds involves surgical debridement along with localized wound irrigation, which requires inpatient care under general anesthesia. This could be followed by, if necessary, defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft, local, or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored. To promote physiological wound healing, a variety of approaches have been subjected to translational research. Beyond conventional wound healing drugs and devices that currently supplement treatments, cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell- or molecule-specific wound healing properties. However, in contrast to the clinical omnipresence of chronic wound healing disorders, there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds. This review provides a comprehensive exploration of current therapies, experimental approaches, and translational studies, offering insights into their efficacy and limitations. Ultimately, we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.

The minimally conscious state: an analysis of current clinical trials registered in ClinicalTrials.gov.

The minimally conscious state (MCS) is a disorder of consciousness described in recent years for patients who have behavioral responses to stimuli that do not meet the classification of chronic vegetative state (CVS) or coma. This distinction is valuable in clinical practice, as minimally conscious patients may require different treatments and may have different long-term outcomes when compared to vegetative states or coma. In this report, we analyzed the ClinicalTrials.gov database to systematically assess all clinical trials regarding MCS. The database was queried using the term "minimally conscious state" in the "condition or disease" search parameter. Of the studies identified, those that had suspended, terminated, or otherwise unknown statuses were excluded. In total, 41 studies were analyzed. The included studies were initiated between 2008 and 2020, with the majority (63%) beginning in 2015 or later. Of the primary intervention modalities included, 15 (37%) evaluated stimulation modalities such as transcranial magnetic stimulation, transcranial direct current stimulation, implantable neurostimulation, vagus nerve stimulation, focused ultrasound and median nerve stimulation. Additionally, 5 (12%) used some form of behavioral therapy. A total of 4 (10%) studies involved pharmaceutical intervention, including dopamine agonists, analgesics and sedatives. Finally, 4 (10%) studies sought to determine the validity of current diagnostic methods and systems used to assess the status of patients in MCSs. Since the definition and criteria for CVS and MCS have been established, these two conditions remain closely associated despite evidence of different patient outcomes and treatment options. Many clinical trials are underway assessing interventions with stimulation. However, the trials are lacking with respect to diagnostic methods and pharmaceutical treatment.

Supraorbital Keyhole Craniotomy in Pediatric Neurosurgery: A Systematic Review of Clinical Outcomes and Cosmetic Outcomes.

BACKGROUND: Supraorbital keyhole craniotomy is a minimally invasive approach used to access the parasellar region with advantages of decreased cortical exposure, simple closure, and decreased risk of postoperative cerebrospinal fluid leak. The incision of this approach, however, has raised cosmetic concerns, especially for pediatric patients. The aim of this study is to assess postoperative complications and cosmeses of the supraorbital keyhole approach for resection of intracranial lesions in pediatric patients. METHODS: A literature search of PubMed, Scopus, and Web of Science databases was performed on June 1, 2021, searching for all studies of pediatric patients undergoing supraorbital keyhole craniotomy for surgical resection of lesions in the anterior fossa/sellar region. RESULTS: Of 729 unique hits, 15 supraorbital keyhole studies reporting on 177 pediatric cases were included in the final review. Quality of all included studies was moderate. Overall, the surgery was well tolerated with a low number of severe adverse events. A wide variety of pathologies were treated with this approach. Complications of surgery included changes in vision, epidural hematoma, subdural hematoma, cerebrospinal fluid leak, and wound infection. At 6 weeks of follow-up, surgical scars in most patients were noted to be minimally detectable. At 3-6 months of follow-up, scars were no longer visible. Cosmetic complications included 5 bone defects, 1 split eyebrow, and 1 case of ptosis. CONCLUSIONS: This study suggests that supraorbital keyhole craniotomy is a safe and effective approach to access the parasellar region in pediatric patients with excellent cosmetic outcomes reported across multiple institutions.