A Novel Hair Restoration Technology Counteracts Androgenic Hair Loss and Promotes Hair Growth in A Blinded Clinical Trial.

Androgenic alopecia (AGA) is a genetically predetermined condition that occurs as a result of stepwise miniaturization of the dermal papilla. During this process, the hair follicle suffers from increasing malnutrition and eventually dies, causing progressive hair loss. We recently highlighted that HIF-1α modulation may counteract hair loss. Here, we aim to demonstrate the positive influence of Tomorrowlabs HIF strengthening factor [HSF] hair restoration technology on hair biology in a monocentric blinded clinical trial over a total period of 9 months. A trial with 20 subjects (4 female and 16 male) and once-daily application of [HSF] hair restoration technology to the scalp was conducted. To assess the tolerability and efficacy of [HSF], testing included dermatological assessment, determination of hair loss by counting after combing, macro images of the head and TrichoScan evaluation of hair density as well as the proportion of anagen hair versus telogen hair. The clinical data show Tomorrowlabs [HSF] hair restoration to be safe and effective to counteract AGA. The use of Tomorrowlabs [HSF] hair restoration resulted in improvements in the clinical parameters of hair quality such as thickness (+7.2%), hair density (+14.3%) and shine and elasticity (+20.3%) during the test period. The effectiveness of the test product was further determined by a significant reduction in hair loss of an average of 66.8% in treatment-responsive subjects after 6 months and an increase in hair growth reaching up to 32.5%, with an average percentage change of 8.4% in all participants and 10.8% in the responsive patients (85% of the study cohort) after 9 months on TrichoScan evaluation. The hair growth cycle was harmonized with the result of an average anagen hair percentage increase of +8.0% and telogen hair percentage reduction of -14.0% shown in the test area. Applicable for both sexes in an alcohol-free formulation, beneficial to scalp health and free of complications or side effects, this novel product provides objectively measurable results counteracting hair loss paired with an improved look and feel of the hair.

Hepatic Functional Pathophysiology and Morphological Damage Following Severe Burns: A Systematic Review and Meta-analysis.

Severe burns are devastating injuries affecting multiple organ systems. Little is known about the influence on the hepatic system and its physiology. This systematic review aimed to assess the current state of research on morphologic liver damage following severe burns. A search was conducted in PubMed, Web of Science, and Cochrane databases using PRISMA guidelines. Outcomes included serum levels of transaminases, fatty infiltration, and necrosis. Weighted individual study estimates were used to calculate pooled transaminase levels and necrosis/fatty infiltration rates using a random-effects approach. Risk ratios or odds ratios and 95% confidence intervals (CIs) were used to describe pooled estimates for risk factors. The literature search retrieved 2548 hits, of which 59 studies were included in qualitative synthesis, and finally 10 studies were included in the meta-analysis. Studies were divided into those reporting autopsies and those reporting changes of serum transaminase levels. The majority of liver autopsies showed fatty infiltration, 82% (95% CI 39-97%) or necrosis of the liver, 18% (95% CI 13-24%). Heterogeneity in studies on hepatic functional damage following severe burns was high. Only a few were well-designed and published in recent years. Many studies could not be included because of insufficient numerical data. There is a high number of patients dying from burns that present with fatty infiltration or necrosis of hepatic tissue. Transaminases were elevated during the initial days postburn. Further research on how severe burns affect the hepatic function and outcome, especially long-term, is necessary. Systematic review registration: PROSPERO:CRD42020206061.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis.

OBJECTIVE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare and severe skin and mucosal reactions that are associated with high mortality. Despite the severity, an evidence-based treatment protocol for SJS/TEN is still lacking. METHOD: In this systematic review and meta-analysis, the PubMed database was searched using the following terms: [Stevens-Johnson syndrome] OR [toxic epidermal necrolysis] AND [therapy] OR [treatment] over a 20-year period (1999-2019) in the German and English language. All clinical studies reporting on the treatment of SJS/TEN were included, and epidemiological and diagnostic aspects of treatment were analysed. A meta-analysis was conducted on all comparative clinical studies that met the inclusion criteria. RESULTS: A total of 88 studies met the inclusion criteria, reporting outcomes in 2647 patients. Treatment was either supportive or used systemic corticosteroid, intravenous immunoglobulin, plasmapheresis, cyclosporine, thalidomide or cyclophosphamide therapy. The meta-analysis included 16 (18%) studies, reporting outcomes in 976 (37%) patients. Systemic glucocorticoids showed a survival benefit for SJS/TEN patients in all analyses compared with other forms of treatment. Cyclosporine treatment also showed promising results, despite being used in a small cohort of patients. No beneficial effects on mortality could be demonstrated for intravenous immunoglobulins. CONCLUSION: Glucocorticoids and cyclosporine may be tentatively recommended as the most promising immunomodulatory therapies for SJS/TEN, but these results should be investigated in future prospective controlled trials.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a 10-year experience in a burns unit.

OBJECTIVE: Stevens-Johnson syndrome (SJS) and its more severe counterpart, toxic epidermal necrolysis (TEN), are skin hypersensitivity reactions defined by epidermal blistering and necrosis. The exact pathophysiology of SJS/TEN is yet to be deciphered, but a number of risk factors have been identified including adverse drug reactions. The diagnosis of SJS/TEN is made on a clinical basis, and treatment consists of supportive care and occasionally immunosuppressants, such as cyclosporin, high-dose intravenous immunoglobulins and/or corticosteroids. Mortality rates can reach 20-25% in adults but are reduced with early intervention. To identify optimal treatment regimens, to better understand the patient cohort affected, and to help identify key risk factors for mortality, we report our experience with the treatment and management of SJS/TEN patients. METHODS: A retrospective review of consecutive patients with SJS and/or TEN admitted to a single burns centre in Germany, between 2008 and 2018, was conducted. The primary outcomes of demographics, clinical course, treatment and patient-reported outcomes were recorded and compared with a control group of patients with burns without a diagnosis of SJS/TEN. RESULTS: A total of 23 patients with SJS/TEN met the inclusion criteria: 17 (74%) with TEN; four (17%) with SJS/TEN overlap; and two (9%) with SJS. Of the patients, 14 (61%) were female and nine (39%) were male. Patient age ranged from 32-78 years (mean: 52 years). A matched cohort of 23 patients with burns served as the control group. All patients received standard of care with a multidisciplinary team. Compared with the control group, SJS/TEN patients had higher mortality rates (n=6, 26% versus n=8, 35%, respectively). The average age of death was 69 years in SJS/TEN patients versus 63 years in control group patients. Age and SCORTEN scores were significant predictors of mortality. CONCLUSIONS: SJS and TEN are rare but extreme reactions of the skin and mucosa, associated with high disease mortality rates. This 10-year single-centre retrospective review contributes to the bank of information for reviews evaluating the management of SJS/TEN patients.

Fungal Infections in Burn Patients.

Background: Fungal burn wound infections are among the most devastating complications in patients who are severely burned. Increasing incidence of burn wound infections caused by fungi led to new challenges in diagnostic and therapeutic approaches. The wide use of broad-spectrum antibiotic agents, an increased prevalence of molds and non-Candida albicans spp., and the variety of available antifungal agents underline the importance of identifying the causative species, to initiate adequate therapy within an adequate timeframe. Methods: Review of the pertinent English and German literature. Results: Fungal burn wound infections go along with a delay of identifying the causative fungus species and can be mistaken for early bacterial burn wound infection. Recently, an increase of uncommon fungal pathogens and fungi resistance against antifungal agents has been reported. Amphotericin B and voriconazole remain the antifungal drugs used most commonly. Conclusions: Adequate therapy remains challenging. Early radical debridement and wound closure play an imperative part, particularly in preventing infections caused by yeasts and molds or any other agent. Prophylactic empiric pharmacologic treatment is reserved for those highly at risk for invasive burn wound infection only. Because of the emergence of drug-resistant fungi, the development of new antifungal drugs is essential for the battle against fungal burn wound infections.

Evaluation of the Online-Presence of ABA-Verified Burn Centers.

Currently, patients seek healthcare information online. An up-to-date online presence is vital for success among the competition amid hospitals. Hospital websites have become an important medium to communicate with patients, provide information about certain diseases/conditions, and advertise healthcare services. This study aims to evaluate burn centers websites verified by the American Burn Association (ABA). The online presence of the 73 ABA-verified burn centers was evaluated according to criteria previously published by Benedikt et al. This included general information on burns, first aid, treatment at the burn unit, research, and education. ABA-verified burn centers were then compared with 48 German-speaking burn centers evaluated by Benedikt et al. Online information about patient care including treatment options and techniques was more often present in ABA-verified burn centers. However, this information was still provided in only half of the websites. Furthermore, ABA-verified burn centers more often used multimedia-based elements and social media platforms. On the other hand, German-speaking burn centers more often provided translations, general information (eg, staff and ward) about the burn center, as well as research and education. This study demonstrates that although many burn centers have well-designed websites, relevant burn-related information on patient care, research, and education is often missing or sparse. Today, most patients look for healthcare information online. Also, applicants for residency or fellowship programs tend to get a first picture of their potential employer on websites or social media. Keeping websites and social media up-to-date and informative can improve recruitment of patients and employees.

Burns: modified metabolism and the nuances of nutrition therapy.

OBJECTIVE: To review the effects of burn injury on nutritional requirements and how this can best be supported in a healthcare setting. METHOD: A literature search for articles discussing nutrition and/or metabolism following burn injury was carried out. PubMed, Embase and Web of Science databases were searched using the key search terms 'nutrition' OR 'metabolism' AND 'burn injury' OR 'burns'. There was no limitation on the year of publication. RESULTS: A total of nine articles met the inclusion criteria, the contents of which are discussed in this manuscript. CONCLUSION: Thermal injury elicits the greatest metabolic response, among all traumatic events, in critically ill patients. In order to ensure burn patients can meet the demands of their increased metabolic rate and energy expenditure, adequate nutritional support is essential. Burn injury results in a unique pathophysiology, involving alterations in endocrine, inflammatory, metabolic and immune pathways and nutritional support needed during the inpatient stay varies depending on burn severity and idiosyncratic patient physiologic parameters.

The Influence of Obesity on Treatment and Outcome of Severely Burned Patients.

Obesity and the related medical, social, and economic impacts are relevant multifactorial and chronic conditions that also have a meaningful impact on outcomes following a severe injury, including burns. In addition to burn-specific difficulties, such as adequate hypermetabolic response, fluid resuscitation, and early wound coverage, obese patients also present with common comorbidities, such as arterial hypertension, diabetes mellitus, or nonalcoholic fatty liver disease. In addition, the pathophysiologic response to severe burns can be enhanced. Besides the increased morbidity and mortality compared to burn patients with normal weight, obese patients present a challenge in fluid resuscitation, perioperative management, and difficulties in wound healing. The present work is an in-depth review of the current understanding of the influence of obesity on the management and outcome of severe burns.

Optimising management of self-inflicted burns: a retrospective review.

OBJECTIVE: Self-inflicted burns typically result in extensive injuries requiring intensive care and attention in a specialised burn unit. Burn units should be familiar with the optimal management of self-inflicted burns, including the psychological and psychiatric treatment. This paper describes the experiences of managing these challenging injuries in a German burn centre. METHODS: A retrospective review of patients with self-inflicted burns admitted to the burn centre between 2000 and 2017. Demographics, details of injury, presence of psychiatric disorder, clinical course, operative management and patient outcomes were recorded and compared with a control group without self-inflicted burns. Outcome measures included graft take rate, complications and need for further surgery. RESULTS: There were a total of 2055 burn patient admissions, with 17 cases (0.8%) of self-inflicted burns. The mean age was 36±11 years with an mean percentage total body surface area (%TBSA) burned of 43.5±22.5% which was not significantly different from the control group (p=0.184). Schizophrenia and personality disorder were the most common diagnoses in the self-inflicted burns patients (n=11; 65%). Of these, four had sustained previous self-inflicted burns. Length of hospital stay was significantly longer in the self-inflicted burn group than in the control group (49.0±16.7 days, respectively, p=0.002). CONCLUSION: Attempted suicide by self-inflicted burns represents <1% of burn admissions. This population demonstrates a high incidence of prior psychiatric disorders. Successful treatment includes multidisciplinary management of acute medical, surgical, and psychiatric care.

Single-Cell Gene Expression Analysis and Evaluation of the Therapeutic Function of Murine Adipose-Derived Stromal Cells (ASCs) from the Subcutaneous and Visceral Compartment.

INTRODUCTION: Adipose-derived stromal cells (ASCs) are a promising resource for wound healing and tissue regeneration because of their multipotent properties and cytokine secretion. ASCs are typically isolated from the subcutaneous fat compartment, but can also be obtained from visceral adipose tissue. The data on their equivalence diverges. The present study analyzes the cell-specific gene expression profiles and functional differences of ASCs derived from the subcutaneous (S-ASCs) and the visceral (V-ASCs) compartment. MATERIAL AND METHODS: Subcutaneous and visceral ASCs were obtained from mouse inguinal fat and omentum. The transcriptional profiles of the ASCs were compared on single-cell level. S-ASCs and V-ASCs were then compared in a murine wound healing model to evaluate their regenerative functionality. RESULTS: On a single-cell level, S-ASCs and V-ASCs displayed distinct transcriptional profiles. Specifically, significant differences were detected in genes associated with neoangiogenesis and tissue remodeling (for example, Ccl2, Hif1α, Fgf7, and Igf). In addition, a different subpopulation ecology could be identified employing a cluster model. Nevertheless, both S-ASCs and V-ASCs induced accelerated healing rates and neoangiogenesis in a mouse wound healing model. CONCLUSION: With similar therapeutic potential in vivo, the significantly different gene expression patterns of ASCs from the subcutaneous and visceral compartments suggest different signaling pathways underlying their efficacy. This study clearly demonstrates that review of transcriptional results in vivo is advisable to confirm the tentative effect of cell therapies.

Wnt Pathway in Bone Repair and Regeneration - What Do We Know So Far.

Wnt signaling plays a central regulatory role across a remarkably diverse range of functions during embryonic development, including those involved in the formation of bone and cartilage. Wnt signaling continues to play a critical role in adult osteogenic differentiation of mesenchymal stem cells. Disruptions in this highly-conserved and complex system leads to various pathological conditions, including impaired bone healing, autoimmune diseases and malignant degeneration. For reconstructive surgeons, critically sized skeletal defects represent a major challenge. These are frequently associated with significant morbidity in both the recipient and donor sites. The Wnt pathway is an attractive therapeutic target with the potential to directly modulate stem cells responsible for skeletal tissue regeneration and promote bone growth, suggesting that Wnt factors could be used to promote bone healing after trauma. This review summarizes our current understanding of the essential role of the Wnt pathway in bone regeneration and repair.

Ultrasound-assisted liposuction provides a source for functional adipose-derived stromal cells.

BACKGROUND AIMS: Regenerative medicine employs human mesenchymal stromal cells (MSCs) for their multi-lineage plasticity and their pro-regenerative cytokine secretome. Adipose-derived mesenchymal stromal cells (ASCs) are concentrated in fat tissue, and the ease of harvest via liposuction makes them a particularly interesting cell source. However, there are various liposuction methods, and few have been assessed regarding their impact on ASC functionality. Here we study the impact of the two most popular ultrasound-assisted liposuction (UAL) devices currently in clinical use, VASER (Solta Medical) and Lysonix 3000 (Mentor) on ASCs. METHODS: After lipoaspirate harvest and processing, we sorted for ASCs using fluorescent-assisted cell sorting based on an established surface marker profile (CD34+CD31-CD45-). ASC yield, viability, osteogenic and adipogenic differentiation capacity and in vivo regenerative performance were assessed. RESULTS: Both UAL samples demonstrated equivalent ASC yield and viability. VASER UAL ASCs showed higher osteogenic and adipogenic marker expression, but a comparable differentiation capacity was observed. Soft tissue healing and neovascularization were significantly enhanced via both UAL-derived ASCs in vivo, and there was no significant difference between the cell therapy groups. CONCLUSIONS: Taken together, our data suggest that UAL allows safe and efficient harvesting of the mesenchymal stromal cellular fraction of adipose tissue and that cells harvested via this approach are suitable for cell therapy and tissue engineering applications.

Continuous hemoadsorption with a cytokine adsorber during sepsis - a review of the literature.

Sepsis is a well-recognized healthcare issue worldwide, ultimately resulting in significant mortality, morbidity and resource utilization during and after critical illness. In its most severe form, sepsis causes multi-organ dysfunction that produces a state of critical illness characterized by severe immune dysfunction and catabolism. Sepsis induces the activation of complement factor via 3 pathways and the release of inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and interleukin-1beta (IL-1ß), resulting in a systemic inflammatory response. The inflammatory cytokines and nitric oxide release induced by sepsis decrease systemic vascular resistance, resulting in profound hypotension. The combination of hypotension and microvascular occlusion results in tissue ischemia and ultimately leads to multiple organ failure. Several clinical and experimental studies have reported that treatment using adsorption of cytokines is beneficial during endotoxemia and sepsis. This review article analyzes the efficacy of CytoSorb® adsorber in reducing the inflammatory response during sepsis. The CytoSorb® adsorber is known to have excellent adsorption rates for inflammatory cytokines such as IL-1ß, IL-6, IL-8, IL-10, and TNF-α. Studies have demonstrated that treatment with cytokine adsorbing columns has beneficial effects on the survival rate and inflammatory responses in animal septic models. Additionally, several cases have been reported in which treatment with cytokine adsorbing columns is very effective in hemodynamic stabilization and in preventing organ failure in critically ill patients. Although further investigations and clinical trials are needed, treatment with cytokine adsorbing columns may play an important role in the treatment of sepsis in the near future.

Medical leech therapy in plastic reconstructive surgery.

The use of Hirudo medicinalis in clinical practice has increased in recent years. The primary indication in plastic surgery has traditionally been venous congestion. However, other reported clinical applications were in varicose veins, thrombophlebitis, and osteoarthritis. In this review, we summarize recent data elucidating the role that medicinal leeches play in the field of plastic surgery.

Wnt signaling induces epithelial differentiation during cutaneous wound healing.

Cutaneous wound repair in adult mammals typically does not regenerate original dermal architecture. Skin that has undergone repair following injury is not identical to intact uninjured skin. This disparity may be caused by differences in the mechanisms that regulate postnatal cutaneous wound repair compared to embryonic skin development and thus we seek a deeper understanding of the role that Wnt signaling plays in the mechanisms of skin repair in both fetal and adult wounds. The influence of secreted Wnt signaling proteins in tissue homeostasis has galvanized efforts to identify small molecules that target Wnt-mediated cellular responses. Wnt signaling is activated by wounding and participates in every subsequent stage of the healing process from the control of inflammation and programmed cell death, to the mobilization of stem cell reservoirs within the wound site. Endogenous Wnt signaling augmentation represents an attractive option to aid in the restoration of cutaneous wounds, as the complex mechanisms of the Wnt pathway have been increasingly investigated over the years. In this review, we summarize recent data elucidating the roles that Wnt signaling plays in cutaneous wound healing process.

Effects of phlebotomy-induced reduction of body iron stores on metabolic syndrome: results from a randomized clinical trial.

BACKGROUND: Metabolic syndrome (METS) is an increasingly prevalent but poorly understood clinical condition characterized by insulin resistance, glucose intolerance, dyslipidemia, hypertension, and obesity. Increased oxidative stress catalyzed by accumulation of iron in excess of physiologic requirements has been implicated in the pathogenesis of METS, but the relationships between cause and effect remain uncertain. We tested the hypothesis that phlebotomy-induced reduction of body iron stores would alter the clinical presentation of METS, using a randomized trial. METHODS: In a randomized, controlled, single-blind clinical trial, 64 patients with METS were randomly assigned to iron reduction by phlebotomy (n = 33) or to a control group (n = 31), which was offered phlebotomy at the end of the study (waiting-list design). The iron-reduction patients had 300 ml of blood removed at entry and between 250 and 500 ml removed after 4 weeks, depending on ferritin levels at study entry. Primary outcomes were change in systolic blood pressure (SBP) and insulin sensitivity as measured by Homeostatic Model Assessment (HOMA) index after 6 weeks. Secondary outcomes included HbA1c, plasma glucose, blood lipids, and heart rate (HR). RESULTS: SBP decreased from 148.5 ± 12.3 mmHg to 130.5 ± 11.8 mmHg in the phlebotomy group, and from 144.7 ± 14.4 mmHg to 143.8 ± 11.9 mmHg in the control group (difference -16.6 mmHg; 95% CI -20.7 to -12.5; P < 0.001). No significant effect on HOMA index was seen. With regard to secondary outcomes, blood glucose, HbA1c, low-density lipoprotein/high-density lipoprotein ratio, and HR were significantly decreased by phlebotomy. Changes in BP and HOMA index correlated with ferritin reduction. CONCLUSIONS: In patients with METS, phlebotomy, with consecutive reduction of body iron stores, lowered BP and resulted in improvements in markers of cardiovascular risk and glycemic control. Blood donation may have beneficial effects for blood donors with METS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01328210 Please see related article: http://www.biomedcentral.com/1741-7015/10/53.