Autophagy, an adaptive catabolic process, plays a cytoprotective role in enabling cellular homeostasis in the innate and adaptive immune systems. Neutrophils, the most abundant immune cells in circulation, are professional killers that orchestrate a series of events during acute inflammation. The recent literature indicates that autophagy has important roles in regulating neutrophil functions, including differentiation, degranulation, metabolism and neutrophil extracellular trap formation, that dictate neutrophil fate. It is also becoming increasingly clear that autophagy regulation is critical for neutrophils to exert their immunological activity. However, evidence regarding the systematic communication between neutrophils and autophagy is insufficient. Here, we provide an updated overview of the function of autophagy as a regulator of neutrophils and discuss its clinical relevance to provide novel insight into potentially relevant treatment strategies.

Hypertrophic scars often develop following burn-related injuries. These scars can be cosmetically unappealing, but associated symptoms of pruritus, pain and restricted range of motion can impair a person’s quality of life. Laser and light therapies offer a minimally invasive, low-risk approach to treatment, with a short postoperative recovery period. As laser technology developed, studies have shown decreased scar thickness, neuropathic pain and need for surgical excision, as well as improved scar pigmentation, erythema, pliability, texture, height and pruritus. In this review, we present the evolution of laser therapy for hypertrophic burn scars, how different types of lasers work, indications, perioperative considerations and guidelines for practice management.

Once scar tissues mature, it is impossible for the surrounding tissue to regenerate normal dermal tissue. Therefore, it is essential to understand the fundamental mechanisms and establish effective strategies to inhibit aberrant scar formation. Hypertrophic scar formation is considered a result of the imbalance between extracellular matrix synthesis and degradation during wound healing. However, the underlying mechanisms of hypertrophic scar development are poorly understood. The purpose of this review was to outline the management in the early stage after wound healing to prevent hypertrophic scar formation, focusing on strategies excluding therapeutic agents of internal use. Treatment aimed at molecular targets, including cytokines, will be future options to prevent and treat hypertrophic scars. More basic studies and clinical trials, including combination therapy, are required to investigate the mechanisms and prevent hypertrophic scar formation.

Background: Itch and pain are common complaints of patients with burn injuries. This study aimed to describe the prevalence and predictors of itch and moderate to severe pain in the first 12 months following a burn injury, and determine the association between itch, moderate to severe pain, work-related outcomes, and health-related quality of life following a burn injury. Methods: Burn patients aged 18 years and older were recruited from five Australian specialist burn units. Patients completed the 36-item Short Form Health Survey Version 2 (SF-36 V2), the Sickness Impact Profile (SIP) work scale, and a specially developed questionnaire relating to itch at 1, 6, and 12 months post-injury. Moderate to severe pain was defined as a score less than 40 on the bodily pain domain of the SF-36 V2. Multivariate mixed-effects regression models were used to identify patient and burn injury predictors of itch and moderate to severe pain. Results: Three hundred and twenty-eight patients were included. The prevalence of itch decreased from 50% at 1 month to 27% at 12 months. Similarly, the prevalence of moderate to severe pain decreased from 23% at 1 month to 13% at 12 months. Compared to patients aged 18-34, the adjusted odds of experiencing any itch were 59% (95% CI: 0.20, 0.82) and 55% (95% CI: 0.22, 0.91) lower for patients aged between 35 and 49 and ≥50 years, respectively. Compared to patients aged 18-34, the adjusted odds of experiencing moderate to severe pain were 3.12 (95% CI: 1.35, 7.20) and 3.42 (95% CI: 1.47, 7.93) times higher for patients aged 35-49 and ≥50 years, respectively. Conclusions: Less than 15% of patients reported moderate or severe pain at 12 months, while approximately one-quarter of the patients reported itch at the same period. The presence of moderate to severe pain was associated with a greater negative impact on health-related quality of life and work outcomes compared to itch. Further research is needed to improve our ability to identify patients at higher risk of persistent itch and pain who would benefit from targeted review and intervention studies.

Background: Burns are one of the major traumas that may affect older individuals. The purpose of this study was to investigate the epidemiological and clinical characteristics of geriatric burns at a major center in south-west China. Methods: This retrospective study was conducted at the Institute of Burn Research, Southwest Hospital of Army Medical University between 2010 and 2016, and the data collected from medical records included admission date, age, gender, premorbid disease, burn etiology, injured anatomical location, burn area and depth, inhalation injury, number of surgeries, length of stay (LOS), clinical outcome, and medical cost. Results: Of the 693 older burn patients included, 60.75% were male and 56.85% were aged 60–69 years. Burns peaked in December–March and June. Flame was the most common cause of burns, making up 51.95% of all cases, and also dominated in the burn patients aged 60–69 years. Limbs were the most common anatomical sites of burns (69.41%), and the median total body surface area (TBSA) was 5% (interquartile range [IQR]: 2%–15%). The percentage of the patients who underwent surgeries and number of surgeries significantly increased in the cases of contact burns, younger age and full-thickness burns. Six deaths resulted in a mortality of 0.9%. The median LOS was 16 days (IQR: 8–29 days), and the main risk factors were more surgeries, better outcomes, and full-thickness burns. The median cost was 20,228 CNY (IQR: 10,457–46,581.5 CNY), and major risk factors included longer LOS, larger TBSA, and more surgeries. Furthermore, compared to the earlier data from our center, the proportion of older adults among all burns (7.50% vs. 4.15%), proportion of flame burns (51.95% vs. 33.90%), and mean age (69.05 years vs. 65.10 years) were significantly higher, while the proportion of premorbidities (16.9% vs. 83.9%), mortality (0.9% vs. 7.5%) and median TBSA (5% vs. 21%) were significantly lower. Conclusions: This study suggested that closer attention should be paid to prevent burn injuries in older people aged 60–69 years, especially males, regarding incidents in the summer and winter, and flame burns. Moreover, tailored intervention strategies based on related risk factors should be under special consideration.

Background: Sepsis is the leading cause of intensive care unit (ICU) admission. The purpose of this study was to explore the prognostic value of the Sequential Organ Failure Assessment (SOFA) score, the Acute Physiological and Chronic Health Evaluation II (APACHE II) score, and procalcitonin (PCT), albumin (ALB), and lactate (LAC) levels in patients with sepsis. Methods: Consecutive adult patients with suspected or documented sepsis at ICU admission were recruited. Their basic vital signs and related auxiliary examinations to determine their PCT and ALB levels and APACHE II score were recorded at ICU admission, and their LAC levels and SOFA scores were recorded for one week after admission. The influence of these variables on hospital mortality was evaluated. Logistic regression was used to derive the Sepsis Hospital Mortality Score (SHMS), a prediction equation describing the relationship between predictors and hospital mortality. The median survival time was calculated by the Kaplan–Meier method. In the validation group, the kappa value was calculated to evaluate the stability of the derived formula. Results: This study included 894 sepsis patients admitted to 18 ICUs in 16 tertiary hospitals. Patients were randomly assigned to an experimental group (626 cases) and validation group (258 cases). In addition, a nonsurvival group (248 patients) of the experimental group was established according to the outcome at the time of discharge. The hospital mortality rate in the experimental group was 39.6% (248/626). Univariate and multivariate regression analyses revealed that the APACHE II score (odds ratio [OR] = 1.178), △SOFA (OR = 1.186), △LAC (OR = 1.157), and SOFA mean score (OR = 1.086) were independently associated with hospital mortality. The SHMS was calculated as logit(p) = 4.715 – (0.164 × APACHE II) – (0.171 × △SOFA) – (0.145 × △LAC) – (0.082 × SOFA mean). A receiver operating characteristic curve was constructed to further investigate the accuracy of the SHMS, with an area under the curve of 0.851 (95% confidence interval [CI] 0.821–0.882; p < 0.001) for hospital mortality. In the low-risk group and high-risk groups, the corresponding median survival times were 15 days and 11 days, respectively. Conclusion: The APACHE II score, △SOFA, △LAC and SOFA mean score were independently associated with hospital mortality in sepsis patients and accurately predicted the hospital mortality rate and median survival time. Data on the median survival time in sepsis patients could be provided to clinicians to assist in the rational use of limited medical resources by facilitating prudent resource allocation. Trial registration: ChiCTR-ECH-13003934, retrospectively registered on August 03, 2013.

Background: Keloids are benign fibroproliferative skin lesions that are difficult to treat and become a lifetime predicament for patients. Several treatment modalities have been put forth, but as yet no satisfactory approach to the prevention or treatment of keloids has been identified. The process of epithelial-to-mesenchymal transition (EMT) has been implicated in keloid scarring, as keloid keratinocytes display an EMT-like phenotype. This study investigated the potential of pirfenidone, an antifibrotic agent, to counteract EMT-like alterations in keloid keratinocytes, including gene expression, cell migratory and proliferative functions. Methods: Normal and keloid keratinocytes were isolated from discarded normal skin tissues and from resected keloid tissues, respectively. Cells were quiesced for 24 h without epidermal growth factor DS-Qi1MCDigital and were exposed to transforming growth factor-beta1 (TGF-β1; 10 ng/mL), with or without pirfenidone (400 μg/mL), for an additional 24 h. The effects of pirfenidone on cytotoxicity, cell migration, cell proliferation, and on expression of genes and proteins involved in EMT were assayed. Statistical significance was determined by two-way ANOVA using Sigma Plot. Results: We found that pirfenidone did not elicit any cytotoxic effect at concentrations up to 1000 μg/mL. A statistically significant dose-dependent decrease in basal cell proliferation rate was noted in both normal and keloid keratinocytes when exposed to pirfenidone at concentrations ranging from 200 to 1000 μg/mL. Pirfenidone significantly decreased basal cell migration in both normal and keloid keratinocytes, but a significant decrease in TGF-β1-induced cell migration was seen only in keloid keratinocytes. Significant inhibition of the expression of TGF-β1-induced core EMT genes, namely hyaluronan synthase 2, vimentin, cadherin-11, and wingless-type MMTV integration site family, member 5A along with fibronectin-1, was observed in both normal and keloid keratinocytes treated with pirfenidone. In addition, the protein levels of vimentin and fibronectin were significantly reduced by pirfenidone (400 μg/mL) in both normal and keloid keratinocytes. Conclusions: For the first time, this study shows the efficacy of pirfenidone in inhibiting the EMT-like phenotype in keratinocytes derived from keloids, suggesting that pirfenidone may counteract a critical contributor of keloid progression and recurrence.

Background: Burns resulting from assaults account for considerable morbidity and mortality among patients with burn injuries around the world. However, it is still unclear whether unfavorable clinical outcomes are associated primarily with the severity of the injuries. To elucidate the direct relationship between burns resulting from assaults and mortality and/or length of hospital stays, we performed this study with the hypothesis that burns from assault would be independently associated with fewer hospital-free days than would burns from other causes, regardless of the severity of burn injuries. Methods: We conducted a retrospective cohort study, using a city-wide burn registry (1996–2017) accounting for 14 burn centers in Tokyo, Japan. Patients who arrived within 24 hours after injury were included, and those with self-inflicted burn injuries were excluded. Patients were divided into two groups according to mechanism of burns (assault vs. accident), and the number of hospital-free days until day 30 after injury (a composite of in-hospital death and hospital length of stay) was compared between the groups. To estimate the probability that an injury would be classified as an assault, we calculated propensity scores, using multivariate logistic regression analyses adjusted for known outcome predictors. We also performed an inverse probability weighting (IPW) analysis to compare adjusted numbers of hospital-free days. Results: Of 7419 patients in the registry with burn injuries during the study period, 5119 patients were included in this study. Of these, 113 (2.2%) were injured as a result of assault; they had significantly fewer hospital-free days than did those with burns caused by accident (18 [27] vs. 24 [20] days; coefficient = −3.4 [−5.5 to −1.3] days; p = 0.001). IPW analyses similarly revealed the independent association between assault burn injury and fewer hospital-free days (adjusted coefficient = −0.6 [−1.0 to −0.1] days; p = 0.009). Conclusions: Burn from assault was independently associated with fewer hospital-free days, regardless of the severity of burn injuries. The pathophysiological mechanism underlying the relationship should be further studied in a prospective observational study.

Traumatic peripheral nerve injury is a worldwide clinical issue with high morbidity. The severity of peripheral nerve injury can be classified as neurapraxia, axonotmesis or neurotmesis, according to Seddon’s classification, or five different degrees according to Sunderland’s classification. Patients with neurotmesis suffer from a complete transection of peripheral nerve stumps and are often in need of surgical repair of nerve defects. The applications of autologous nerve grafts as the golden standard for peripheral nerve transplantation meet some difficulties, including donor nerve sacrifice and nerve mismatch. Attempts have been made to construct tissue-engineered nerve grafts as supplements or even substitutes for autologous nerve grafts to bridge peripheral nerve defects. The incorporation of stem cells as seed cells into the biomaterial-based scaffolds increases the effectiveness of tissue-engineered nerve grafts and largely boosts the regenerative process. Numerous stem cells, including embryonic stem cells, neural stem cells, bone marrow mesenchymal stem cells, adipose stem cells, skin-derived precursor stem cells and induced pluripotent stem cells, have been used in neural tissue engineering. In the current review, recent trials of stem cell-based tissue-engineered nerve grafts have been summarized; potential concerns and perspectives of stem cell therapeutics have also been contemplated.

Complex facial trauma requires complex repair and solutions. This process is challenging for the surgeon who seeks to manage the expectations of the patient and family while achieving the best possible result. Historically, the use of pedicled flaps, and then free tissue transfer, were the primary techniques utilized. Advancements in soft-tissue reconstruction, such as perforator flaps and pre-expanded and prefabricated flaps, allow refinement of the soft-tissue reconstruction process to create the best initial soft-tissue coverage. The advent of contemporary technologies, such as virtual surgical planning, stereolithography and customized implants and plates, facilitates a tailored approach to the patient’s reconstructive needs for precise bony reconstruction. When surgical and technological techniques are combined in complementary multistage reconstructions, better reconstructive and aesthetic outcomes are achievable than ever before. In this review, the authors present a summary of the management of complex facial trauma based on the senior author’s broad experience. Initial management and contemporary reconstructive techniques and technology to provide optimal outcomes are reviewed. A case series of complex facial traumas and their reconstructive process is also presented to demonstrate how complementary staged procedures can yield an optimal result. We believe the reconstructive surgeon managing complex facial trauma should strive to incorporate contemporary technologies and techniques into their armamentarium to provide the best patient care.

Background: Hard-to-heal wounds are often compromised by the presence of biofilm. This presents an infection risk, yet traditional antimicrobial wound care products and systemic antibiotics are often used despite the uncertainty of therapeutic success and wound progression. The aim of this study was to investigate the clinical impact of a next-generation anti-biofilm Hydrofiber wound dressing (AQUACEL Ag+ Extra[AQAg+ E]) in hard-to-heal wounds that had previously been treated unsuccessfully with traditional silver-, iodine-or polyhexamethylene biguanide (PHMB)-containing dressings and products and/or systemic antibiotics. Methods: Clinical case study evaluations of the anti-biofilm dressing were conducted, where deteriorating or stagnant wounds were selected by clinicians and primary dressings were replaced by the anti-biofilm dressing for up to 4 weeks, or as deemed clinically appropriate, with monitoring via case report forms. The data was stratified for cases where traditional silver-, iodine-or PHMB-containing products, or systemic antibiotics, had been used prior to the introduction of the anti-biofilm dressing. Results: Sixty-five cases were identified for inclusion, wounds ranging in duration from 1 week to 20 years (median: 12 months). In 47 (72%) cases the wounds were stagnant, while 15 (23%) were deteriorating; 3 wounds were not recorded. After an average of 4.2 weeks of management with the anti-biofilm dressing (range: 1–11 weeks), in 11 (17%) cases the wounds had healed (i.e. complete wound closure), 40 (62%) wounds improved, 9 (14%) wounds remained the same and 5 (8%) wounds deteriorated. Conclusions: The introduction of this anti-biofilm dressing into protocols of care that had previously involved wound management with traditional antimicrobial products and/or antibiotics was shown to facilitate improvements in the healing status of most of these hard-to-heal wounds. Dressings containing proven anti-biofilm technology, in combination with antimicrobial silver and exudate management technology, appear to be an effective alternative to traditional antimicrobial products and antibiotics in the cases presented here. The use of antimicrobial wound dressings that contain anti-biofilm technology may have a key role to play in more effective wound management and antibiotic stewardship.

Background: Reconstruction of upper and lower lip subunits is a complicated and elusive challenge. For patients affected by defects involving upper and lower lip subunits, a technique able to reconstruct both aesthetic units with matched colour, sufficient contours and similar texture would be ideal. In this study, we present our experience with upper and lower lip reconstruction using the pre-expanded bipedicled visor flap. Methods: From January 2014 to January 2017, 12 male patients presenting with defects of the upper and lower lip subunits were treated using this surgical technique. After a period of expansion of the scalp flap of over 6 months, the bipedicled visor flap was raised from both the parietal regions and rotated to resurface the defect. Delay and section of the pedicle were then performed. Results: Twelve male patients with postburn scars aged 22 to 48 years (mean: 34 years) were successfully treated with no major complications. The donor site was closed primarily in all cases. Subsequent flap debulking and minor revisions were performed under local anaesthesia between 6 and 12 months postoperatively. Conclusions: The pre-expanded bipedicled visor flap provides an effective and reliable option for upper and lower lip reconstruction with excellent colour and texture. It is feasible to achieve these results simultaneously from a single donor site by using a pre-expanded bipedicled visor flap.

Numerous studies have shown that macrophages can orchestrate the microenvironment from the early stage of wound healing to the later stages of scar formation. However, few reviews have highlighted the significance of macrophages during the formation of abnormal scars. The purpose of this review was to outline the polarization of macrophages from early to late stage of pathological scar formation, focusing on spatiotemporal diversity of M1 and M2 macrophages. In this review, the role of macrophages in the formation of hypertrophic scars and keloids is summarized in detail. First, an increased number of M2 cells observed before injuries are significantly associated with susceptibility to abnormal scar pathogenesis. Second, decreased expression of M1 at the early stage and delayed expression of M2 at the late stage results in pathological scar formation. Third, M2 cells are highly expressed at both the margin and the superficial region, which is consistent with the invasive property of keloids. Finally, this review helps to characterize strategies for the prediction and prevention of pathological scar formation.

Background: Frostbite is a cold injury that has the potential to cause considerable morbidity and long-term disability. Despite the complexity of these patients, diagnostic and treatment practices lack standardization. Thrombolytic therapy has emerged as a promising treatment modality, demonstrating impressive digit salvage rates. We review our experience with thrombolytic therapy for severe upper extremity frostbite. Methods: Retrospective data on all frostbite patients evaluated at our institution from December 2017 to March 2018 was collected. A subgroup of patients with severe frostbite treated with intra-arterial thrombolytic therapy (IATT) were analysed. Results: Of the 17 frostbite patients treated at our institution, 14 (82%) were male and the median age was 31 (range: 19–73). Substance misuse was involved in a majority of the cases (58.8%). Five (29.4%) patients with severe frostbite met inclusion criteria for IATT and the remaining patients were treated conservatively. Angiography demonstrated a 74.5% improvement in perfusion after tissue plasminogen activator thrombolysis. When comparing phalanges at risk on initial angiography to phalanges undergoing amputation, the phalangeal salvage rate was 83.3% and the digit salvage rate was 80%. Complications associated with IATT included groin hematoma, pseudoaneurysm and retroperitoneal hematoma. Conclusions: Thrombolytic therapy has the potential to greatly improve limb salvage and functional recovery after severe frostbite when treated at an institution that can offer comprehensive, protocoled thrombolytic therapy. A multi-center prospective study is warranted to elucidate the optimal treatment strategy in severe frostbite.

Background: Researchers have explored the use of adipose-derived stem cells (ASCs) as a cell-based therapy to cover wounds in burn patients; however, underlying mechanistic aspects are not completely understood. We hypothesized that ASCs would improve post-burn wound healing after eschar excision and grafting by increasing wound blood flow via induction of angiogenesis-related pathways. Methods: To test the hypothesis, we used an ovine burn model. A 5 cm² full thickness burn wound was induced on each side of the dorsum. After 24 hours, the burned skin was excised and a 2 cm² patch of autologous donor skin was grafted. The wound sites were randomly allocated to either topical application of 7 million allogeneic ASCs or placebo treatment (phosphate-buffered saline [PBS]). Effects of ASCs culture media was also compared to those of PBS. Wound healing was assessed at one and two weeks following the application of ASCs. Allogeneic ASCs were isolated, cultured and characterized from non-injured healthy sheep. The identity of the ASCs was confirmed by flow cytometry analysis, differentiation into multiple lineages and gene expression via real-time polymerase chain reaction. Wound blood flow, epithelialization, graft size and take and the expression of vascular endothelial growth factor (VEGF) were determined via enzyme-linked immunosorbent assay and Western blot. Results: Treatment with ASCs accelerated the patch graft growth compared to the control (p < 0.05). Topical application of ASCs significantly increased wound blood flow (p < 0.05). Expression of VEGF was significantly higher in the wounds treated with ASCs compared to control (p < 0.05). Conclusions: ASCs accelerated grafted skin growth possibly by increasing the blood flow via angiogenesis induced by a VEGF-dependent pathway.

Background: Human positive cofactor 4 (PC4) was initially characterized as a multifunctional transcriptional cofactor, but its role in skin wound healing is still unclear. The purpose of this study was to explore the role of PC4 in skin wound healing through PC4 knock-in mouse model. Methods: A PC4 knock-in mouse model (PC4+/+) with a dorsal full-thickness wound was used to investigate the biological functions of PC4 in skin wound healing. Quantitative PCR, Western blot analysis and immunohistochemistry were performed to evaluate the expression of PC4; Sirius red staining and immunofluorescence were performed to explore the change of collagen deposition and angiogenesis. Proliferation and apoptosis were detected using Ki67 staining and TUNEL assay. Primary dermal fibroblasts were isolated from mouse skin to perform cell scratch experiments, cck-8 assay and colony formation assay. Results: The PC4+/+ mice were fertile and did not display overt abnormalities but showed an obvious delay in cutaneous healing of dorsal skin. Histological staining showed insufficient re-epithelialization, decreased angiogenesis and collagen deposition, increased apoptosis and decreased cell proliferation in PC4+/+ skin. Our data also showed decreased migration rate and proliferation ability in cultured primary fibroblasts from PC4+/+ mice in vitro. Conclusions: This study suggests that PC4 might serve as a negative regulator of skin wound healing in mice.

Background: Chronic pain, unrelated to the burn itself, can manifest as a long-term complication in patients sustaining burn injuries. The purpose of this study was to determine the prevalence of chronic neuropathic pain (CNP) and compare burn characteristics between patients who developed CNP and patients without CNP who were treated at a burn center. Methods: A single-center, retrospective analysis of 1880 patients admitted to the adult burn center was performed from 1 January 2014 to 1 January 2019. Patients included were over the age of 15 years, sustained a burn injury and were admitted to the burn center. CNP was diagnosed clinically following burn injury. Patients were excluded from the definition of CNP if their pain was due to an underlying illness or medication. Comparisons between patients admitted to the burn center with no pain and patients admitted to the burn center who developed CNP were performed. Results: One hundred and thirteen of the 1880 burn patients developed CNP as a direct result of burn injury over 5 years with a prevalence of 6.01%. Patients who developed CNP were a significantly older median age (54 years vs. 46 years, p = 0.002), abused alcohol (29% vs. 8%, p < 0.001), abused substances (31% vs. 9%, p < 0.001), were current daily smokers (73% vs. 33%, p < 0.001), suffered more full-thickness burns (58% vs. 43%, p < 0.001), greater median percent of total body surface area (%TBSA) burns (6 vs. 3.5, p < 0.001), were more often intubated on mechanical ventilation (33% vs. 14%, p < 0.001), greater median number of surgeries (2 vs. 0, p < 0.001) and longer median hospital length of stay (LOS) (10 days vs. 3 days, p < 0.001), compared to those who did not develop CNP, respectively. Median patient follow-up was 27 months. Conclusions: The prevalence of CNP over 5 years was 6.01% in the burn center. Older ages, alcohol abuse, substance abuse, current daily smoking, greater percent of total body surface area (%TBSA) burns, third degree burns, being intubated on mechanical ventilation, having more surgeries and longer hospital LOS were associated with developing CNP following burn injury, compared to patients who did not develop CNP following burn injury.

Background: Sacral pressure ulcers are associated with high morbidity and, in some cases, result in mortality from severe sepsis. Local flaps are frequently used for reconstruction of stage III and IV pressure ulcers. An ideal flap should be simple to design, have a reliable vascular supply and minimal donor site morbidity. Our study evaluates the use of a bilobed flap based on the superficial branch of the superior gluteal artery or the posterior branch of the fourth lumbar artery to reconstruct the sacral pressure ulcer. Case presentation: We performed a retrospective analysis of paraplegic patients with sacral pressure ulcers treated with our bilobed flaps from January 2015 to December 2019. A description of our management, operative protocol, outcome and complications is outlined. Seven paraplegic patients (6 male, 1 female; average age 53.1 years) with sacral pressure ulcers were treated with our bilobed flap based on the superficial branch of the superior gluteal artery or the posterior branch of the fourth lumbar artery. The average size of the pressure ulcers was 7 × 5 cm (range 6.2 × 4.5 cm to 11 × 10 cm). All 7 flaps survived. The patients were followed up for 12 months without significant complications, such as flap necrosis or recurrence. Conclusions: The superficial branch of the superior gluteal artery or the posterior branch of the fourth lumbar artery reliably supplies the bilobed flap. The superior cluneal nerve can be included in the design. The technique is simple and reliable. It should be included in the reconstructive algorithm for the management of sacral pressure ulcers.

Pathological scars might cause a distorted appearance and restricted mobility, and the study of scar pathophysiology has been hindered by the absence of a reliable model. In this study, we introduce a model with a modified device to induce controlled tension on a wound healing by secondary intention to overcome the shortcomings of the model generated by Aarabi et al. We investigated and recommend an induction of 0.1 N/mm² tension on day 7 for 14 days to mimic the characteristics of human scars. A 3.5-fold increase in scar tissue and a 2-fold increase in collagen production were induced by the modified model. Histologically, the modified method increased scar thickness. However, no significant difference was found in cell density between the two groups. This modified procedure significantly increased scar tissue, which could be used for further cellular and biomolecular research. The mechanical force applied to the wound became measurable and controllable. This method is more convenient for researchers to observe in real-time and for providing timely adjustments of the tension used in this modified model.

Background: Severe burn injuries create large skin defects that render the host susceptible to bacterial infections. Burn wound infection often causes systemic sepsis and severe septicemia, resulting in an increase in the mortality of patients with severe burn injuries. Therefore, appropriate wound care is important to prevent infection and improve patient outcomes. However, it is difficult to heal a third-degree burn injury. The aim of this study was to investigate whether hyperdry human amniotic membrane (HD-AM) could promote early granulation tissue formation after full-thickness skin excision in third-degree burn injury sites in mice. Methods: After the development of HD-AM and creation of a third-degree burn injury model, the HD-AM was either placed or not placed on the wound area in the HD-AM group or HD-AM group, respectively. The groups were prepared for evaluation on postoperative days 1, 4 and 7. Azan staining was used for granulation tissue evaluation, and estimation of CD163, transforming growth factor beta-1 (TGF-β1), vascular endothelial growth factor (VEGF), CD31, alpha-smooth muscle actin (α-SMA) and Iba1 expression was performed by immunohistochemical staining. Quantitative reverse-transcription polymerase chain reaction (PCR) was used to investigate gene expression of growth factors, cell migration chemokines and angiogenic and inflammatory markers. Results: The HD-AM group showed significant early and qualitatively good growth of granulation tissue on the full-thickness skin excision site. HD-AM promoted early-phase inflammatory cell infiltration, fibroblast migration and angiogenesis in the granulation tissue. Additionally, the early infiltration of cells of the immune system was observed. Conclusions: HD-AM may be useful as a new wound dressing material for full-thickness skin excision sites after third-degree burn injuries, and may be a new therapeutic technique for improving the survival rate of patients with severe burn injuries.

Background: Smoke inhalation injury increases overall burn mortality. Locally applied heparin attenuates lung injury in burn animal models of smoke inhalation. It is uncertain whether local treatment of heparin is benefit for burn patients with inhalation trauma. We systematically reviewed published clinical trial data to evaluate the effectiveness of nebulized heparin in treating burn patients with inhalation injury. Methods: A systematic search was undertaken in PubMed, the Cochrane Library, Embase, Web of Science, the Chinese Journals Full-text Database, the China Biomedical Literature Database and the Wanfang Database to obtain clinical controlled trails evaluating nebulized heparin in the treatment of burn patients with inhalation injury. Patient and clinical characteristics, interventions and physiological and clinical outcomes were recorded. Cochrane Risk of Bias Evaluation Tool and the Newcastle–Ottawa Scale were used to evaluate data quality. Potential publication bias was assessed by Egger’s test. A sensitivity analysis was conducted to assess the stability of the results. The meta-analysis was conducted in R 3.5.1 software. Results: Nine trials were eligible for the systematic review and meta-analysis. Nebulized heparin can reduce lung injury and improve lung function in burn patients with inhalation injury without abnormal coagulation or bleeding, but the findings are still controversial. Mortality in the heparin-treated group was lower than that of the traditional treatment group (relative risk (RR) 0.75). The duration of mechanical ventilation (DOMV) was shorter in the heparin-treated group compared to the traditional treatment group (standardized mean difference (SMD) −0.78). Length of hospital stay was significantly shorter than that in the traditional treatment group (SMD −0.42), but incidence rates of pneumonia and unplanned reintubation were not significantly different in the study groups (RRs 0.97 and 0.88, respectively). No statistically significant publication biases were detected for the above clinical endpoints (p > 0.05). Conclusions: Based on conventional aerosol therapy, heparin nebulization can further reduce lung injury, improve lung function, shorten DOMV and length of hospital stay, and reduce mortality, although it does not reduce the incidence of pneumonia and/or the unplanned reintubation rate.

In recent years, as living standards have continued to improve, the number of diabetes patients in China, along with the incidence of complications associated with the disease, has been increasing. Among these complications, diabetic foot disease is one of the main causes of disability and death in diabetic patients. Due to the differences in economy, culture, religion and level of medical care available across different regions, preventive and treatment methods and curative results for diabetic foot vary greatly. In multidisciplinary models built around diabetic foot, the timely assessment and diagnosis of wounds and appropriate methods of prevention and treatment with internal and external surgery are key to clinical practice for this pathology. In 2019, under the leadership of the Jiangsu Medical Association and Chinese Diabetes Society, the writing group for the Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition) was established with the participation of scholars from the specialist areas of endocrinology, burn injury, vascular surgery, orthopedics, foot and ankle surgery and cardiology. Drawing lessons from diabetic foot guidelines from other countries, this guide analyses clinical practices for diabetic foot, queries the theoretical basis and grades and gives recommendations based on the characteristics of the pathology in China. This paper begins with assessments and diagnoses of diabetic foot, then describes treatments for diabetic foot in detail, and ends with protections for high-risk feet and the prevention of ulcers. This manuscript covers the disciplines of internal medicine, surgical, nursing and rehabilitation and describes a total of 50 recommendations that we hope will provide procedures and protocols for clinicians dealing with diabetic foot.

Background: Patients with burns present with different clinical features depending on the types of burn injury and burn patients with lower levels of vitamin D have worse prognoses and more complications. The study aims to investigate the association between vitamin D levels and burn factors according to each burn type in relation to early intensive rehabilitation therapy initiated for inpatients with burns. Methods: In this retrospective study, we enrolled 757 of 1716 inpatients who underwent rehabilitative therapy between May 2013 and April 2017. Burn types were divided into flame burn, electrical burn and other burns, including scalding, contact and chemical burns. Age, burned body surface area (BSA), wound healing time (WHT), length of hospital stay (LOS) and body mass index were analysed between vitamin D deficient and non-deficient patient groups using Student's t-tests, or Mann-Whitney U test and among three burn types using one-way analysis of variance (ANOVA) or Kruskal-Wallis one-way ANOVA. The relationship between vitamin D levels and burn factors was evaluated using Pearson's or Spearman's correlation coefficient tests, and multiple linear regression analysis in different burn groups. Results: In total, 88.9% patients were vitamin D deficient, and these patients had a larger burned BSA (p = 0.015) and longer WHT and LOS (all p < 0.001) than non-deficient patients. Burned BSA, WHT and vitamin D levels showed significant differences in their mean values according to three burn types (all p < 0.001). WHT was a communal factor significantly associated with vitamin D levels in all three burn types (p < 0.05). The WHT cut-off points to predict vitamin D deficiency were 55 days for flame burn (p < 0.001) and 62.5 days for electrical burn (p = 0.001). Conclusions: WHT across all three burn types was a common factor associated with vitamin D levels for inpatients with burns who had undergone rehabilitative therapy. Electrical burn patients with vitamin D deficiency, even those with a low burned BSA percentage, showed prolonged wound healing over a two-month post-burn period. Independent of burned BSA, nutritional intervention concerning vitamin D in relation to burn wound healing should be considered to guide early initiation of intensive rehabilitation therapy.

Currently, there are no harmonized guidelines which govern skin banking in the Asia Pacific region. Therefore, skin banks are either unregulated or rely on their nation’s legislation or international accreditation to uphold their quality standards. A new set of skin banking guidelines was developed through a comprehensive review and collation of best international practices for the Asia Pacific Burn Association (APBA) members, from donor screening and testing, to skin recovery, processing, storage and distribution, and quality assurance. National regulatory requirements reviewed include the European directives, Australia’s Therapeutic Goods Administration and Singapore’s tissue banking standards. Further technical and quality management recommendations are referenced from the American Association of Tissue Banks (AATB), the United States Food and Drug Administration standards and guidance documents, various relevant European guides, Japanese Society of Tissue Transplantation guidelines and the Asia Pacific Association of Surgical Tissue Banking. Adapted mainly from the AATB standards, the new Asia Pacific Burn Association Guidelines for Skin Banking in Therapeutic Applications offer a comprehensive manual, addressing: governance and contracts; staff responsibilities; quality management; facilities, equipment and supplies management; donor consent and testing; and recommendations of good practices pertaining to skin recovery, processing, storage and distribution. Besides complementing current generic regulations, they provide technical specifications of major aspects unaddressed in most legislations. This inaugural set of new regional skin banking guidelines would be a start for regional members of the APBA to adopt, and will hopefully culminate in a set of standards so that, in the long run, skin allografts from this region can be of similar quality, which can simplify import process and facilitate the exchange of allografts between members.

Background: Diabetic wounds are one of the most common and serious complications of diabetes mellitus, characterized by the dysfunction of wound-healing-related cells in quantity and quality. Our previous studies revealed that human amniotic epithelial cells (hAECs) could promote diabetic wound healing by paracrine action. Interestingly, numerous studies demonstrated that exosomes derived from stem cells are the critical paracrine vehicles for stem cell therapy. However, whether exosomes derived from hAECs (hAECs-Exos) mediate the effects of hAECs on diabetic wound healing remains unclear. This study aimed to investigate the biological effects of hAECs-Exos on diabetic wound healing and preliminarily elucidate the underlying mechanism. Methods: hAECs-Exos were isolated by ultracentrifugation and identified by transmission electron microscopy, dynamic light scattering and flow cytometry. A series of in vitrofunctional analyses were performed to assess the regulatory effects of hAECs-Exos on human fibroblasts (HFBs) and human umbilical vein endothelial cells (HUVECs) in a high-glycemic microenvironment. High-throughput sequencing and bioinformatics analyses were conducted to speculate the related mechanisms of actions of hAECs-Exos on HFBs and HUVECs. Subsequently, the role of the candidate signaling pathway of hAECs-Exos in regulating the function of HUVECs and HFBs, as well as in diabetic wound healing, was assessed. Results: hAECs-Exos presented a cup-or sphere-shaped morphology with a mean diameter of 105.89 ± 10.36 nm, were positive for CD63 and TSG101 and could be internalized by HFBs and HUVECs. After that, hAECs-Exos not only significantly promoted the proliferation and migration of HFBs, but also facilitated the angiogenic activity of HUVECs in vitro. High-throughput sequencing revealed enriched miRNAs of hAECs-Exos involved in wound healing. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses have shown that the target genes of the top 15 miRNAs were highly enriched in the PI3K-AKT pathway. Further functional studies demonstrated that the PI3K-AKT-mTOR pathway was necessary for the induced biological effects of hAECs-Exos on HFBs and HUVECs, as well as on wound healing, in diabetic mice. Conclusions: Our findings demonstrated that hAECs-Exos represent a promising, novel strategy for diabetic wound healing by promoting angiogenesis and fibroblast function via activation of the PI3K-AKT-mTOR pathway.

Chronic wounds include, but are not limited to, radiation ulcers, pressure ulcers, vascular ulcers and diabetic foot ulcers. These chronic wounds can persist for years without healing and severe ulcers may lead to amputation. Unfortunately, the underlying pathologies of refractory chronic wounds are not fully characterized, and new treatments are urgently needed. Recently, increasing evidence has indicated that cell senescence plays an important role in the development of chronic wounds, and preventing cell senescence or removing senescent cells holds promise as a new therapeutic strategy. In this review, we aim to probe these latest findings to promote the understanding of cellular senescence in the pathological process and potential management of chronic wounds.

Skin regeneration represents a promising line of management for patients with skin loss, including burn victims. The current approach of spraying single cells over the defective areas results in variable success rates in different centers. The modern approach is to synthesize a multilayer skin construct that is based on autologous stem cells. One of the main complications with different types of transplants is sloughing due to the absence of proper vascularization. Ensuring proper vascularization will be crucial for the integration of skin constructs with the surrounding tissues. Combination of the right cells with scaffolds of proper physico-chemical properties, vascularization can be markedly enhanced. The material effect, pore size and adsorption of certain proteins, as well as the application of appropriate growth factors, such as vascular endothelial growth factors, can have an additive effect. A selection of the most effective protocols is discussed in this review.

Burns to the face affect a part of the body that cannot be hidden and thus exposes potentially major changes in appearance to society. Therefore, it is incumbent upon the caregiver to optimize healing and minimize scarring. The goal for partial-thickness burns is to have them heal within 2–3 weeks to minimize healing time. For full-thickness burns there needs to be strategies to optimize the outcomes for skin grafting and minimize scarring. The goal of this review is to discuss the best way to improve the outcomes of these devastating injuries.

Background: One of the most pervasive complications of burn injury is wound progression, characterized by continuous tissue destruction in untreated wounds, which leads to wound infection, inflammation, oxidative stress and excessive scar formation. We determined whether additional tissue destruction could be attenuated with Livionex formulation (LF) lotion, which contains a metal-chelating agent and reduces inflammation in burn wounds. Methods: We subjected male Sprague Dawley rats to a 2% total body surface area (TBSA) burn using a brass comb model and topically applied LF lotion (containing ethylenediaminetetraacetic acid and methyl sulfonyl methane) to the affected area every 8 hours over 3 days. Inflammatory cytokine levels, cell apoptosis and wound healing were compared in LF lotion-treated and untreated rats. Statistical analysis was performed using a one-way analysis of variance in conjunction with Tukey’s post-hoc test. Results: Serum inflammatory cytokines were not detectable after 3 days, suggesting that small burn wounds induce only an immediate, localized inflammatory response. Microscopy revealed that LF lotion improved burn site pathology. Deoxynucleotidyl transferase biotin-d-UTP nick-end labeling staining showed reduced cell death in the LF-treated samples. LF lotion prevented the spread of tissue damage, as seen by increased amounts of Ki-67-positive nuclei in the adjacent epidermis and hair follicles. Tumor necrosis factor-alpha, interleukin-6 and inducible nitric oxide synthase levels in LF-treated skin sections from burned rats were comparable to the levels observed in unburned control sections, indicating that LF lotion reduces inflammation in and around the burn site. Conclusions: These results establish LF lotion as a therapeutic agent for reducing inflammatory stress, cell death and tissue destruction when applied immediately after a burn injury. Further studies of LF lotion on large TBSA burns will determine its efficacy as an emergency treatment for reducing long-term morbidity and scarring.

Background: Keloid is a fibrotic dermal disease characterized by an abnormal increase in fibroblast proliferation and invasion. These pathological behaviours may be related to the heterogeneity of keloid fibroblasts (KFs); however, because of a lack of effective biomarkers for KFs it is difficult to study the underlying mechanism. Our previous studies revealed that the expansion of CD26+ KFs was responsible for increased keloid proliferation and invasion capabilities; the intrinsic relationship and mechanism between CD26 and keloid is therefore worthy of further investigation. The aim of this study was to explore molecular mechanisms in the process of CD26 upregulated KFs proliferation and invasion abilities, and provide more evidence for CD26 as an effective biomarker of keloid and a new clinical therapeutic target. Methods: Flow cytometry was performed to isolate CD26+/CD26− fibroblasts from KFs and normal fibroblasts. To generate stably silenced KFs for CD26 and insulin-like growth factor-1 receptor (IGF-1R), lentiviral particles encoding shRNA targeting CD26 and IGF-1R were used for transfection. Cell proliferations were analysed by cell counting kit-8 assay and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assay. Scratching assay and transwell assay were used to assess cell migration and invasion abilities. To further quantify the regulatory role of CD26 expression in the relevant signalling pathway, RT-qPCR, western blot, ELISA, PI3K activity assay and immunofluorescence were used. Results: Aberrant expression of CD26 in KFs was proven to be associated with increased proliferation and invasion of KFs. Furthermore, the role of the IGF-1/IGF-1 receptor axis was also studied in CD26 and was found to upregulate KF proliferation and invasion. The PI3K/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway was shown to affect CD26-regulated KF proliferation and invasion by increasing phosphorylation levels of S6 kinase and 4E-binding protein. Conclusions: CD26 can be the effective biomarker for KFs, and its expression is closely related to proliferation and invasion in keloids through the IGF-1-induced PI3K/AKT/mTOR pathway. This work provides a novel perspective on the pathological mechanisms affecting KFs and therapeutic strategies against keloids.

Background: Acinetobacter baumannii (A. baumannii) is one of the pivotal pathogens responsible for nosocomial infections, especially in patients with low immune response, and infection with carbapenem-resistant A. baumannii has been increasing in recent years. Rapid and accurate detection of carbapenem-resistance genes in A. baumannii could be of immense help to clinical staff. Methods: In this study, a 15-µL reaction system for recombinase polymerase amplification (RPA) was developed and tested. We collected 30 clinical isolates of A. baumannii from the Burn Institute of Southwest Hospital of Third Military Medical University (Army Medical University) for 6 months and tested antibiotic susceptibility using the VITEK 2 system. A. baumannii was detected based on the bla_OXA-51 gene by PCR, qPCR and 15 µL-RPA, respectively. Sensitivity and specificity were evaluated. In addition, PCR and 15 µL-RPA data for detecting the carbapenem-resistance gene bla_OXA-23 were comparatively assessed. Results: The detection limit of the bla_OXA-51 gene by 15 µL RPA was 2.86 CFU/ml, with sensitivity comparable to PCR and qPCR. No positive amplification signals were detected in non-Acinetobacter isolates, indicating high specificity. However, only 18 minutes were needed for the 15 µL RPA assay. Furthermore, an antibiotic susceptibility test showed that up to 90% of A. baumannii strains were resistant to meropenem and imipenem; 15 µL RPA data for detecting bla_OXA-23 showed that only 10% (n = 3) of A. baumannii isolates did not show positive amplification signals, and the other 90% of (n = 27) isolates were positive, corroborating PCR results. Conclusion: We demonstrated that the new 15 µL RPA assay for detecting bla_OXA-23 in A. baumannii is faster and simpler than qPCR and PCR. It is a promising alternative molecular diagnostic tool for rapid and effective detection of A. baumannii and drug-resistance genes in the field and point-of-care testing.

Background: In modern-day burn care, advanced age remains an important predictor for mortality among burn victims. In this study, we compared the complete treatment trajectory (including pre-hospital and surgical treatment) and the outcomes between an elderly burn population and a younger adult burn population. Methods: In this nationwide study, data from the Dutch Burn Repository were used. This is a uniform national registration for Dutch specialized burn care. All adult patients that were admitted to one of the three Dutch burn centres from the period 2009 to 2015 were included in the analysis. Burn patients were considered as elderly when ≥65 years of age, and were then further subdivided into three age categories: 65–74, 75–85 and 85+ years. Younger adults in the age category 18–64 years were used as the reference group. Surgical management was studied comprehensively and included timing of surgery, the number of procedures and details on the surgical technique, especially the technique used for debridement and the grafting technique that was applied. For the comparison of clinical outcome, the following parameters were included: mortality, wound infections, length of stay/TBSA (total body surface area) burned, discharge disposition and secondary reconstructions. Results: During the study period, 3155 adult patients were included (elderly, n = 505). Burn severity, reflected by the median TBSA, varied between 3.2–4.0% and was comparable, but aetiology and pre-hospital care were different between elderly and the younger adult reference group. Surgical treatment was initiated significantly faster in elderly burn patients (p < 0.001). Less selective techniques for surgical debridement were used in the elderly burns patients (hydrosurgery, 42.0% vs 23.5–22.6%), and on the other hand more avulsion (5.3% vs 7.3–17.6%) and primary wound closure (6.7% vs 24.5%). The most frequently used grafting technique was meshed skin grafts (79.2–88.6%); this was not related to age. Mortality increased rapidly with a higher age and showed a high peak in the 85+ category (23.8%). Furthermore, considerable differences were found in hospital discharge disposition between the elderly and the reference group. Conclusions: In conclusion, elderly burn patients who require specialized burn care are vulnerable and medically challenging. Differences in aetiology, comorbidity, physiology and the management prior to admission possibly affect the initial surgical management and result in significantly worse outcomes in elderly. Elderly patients need optimal, timely and specialized burn care to enhance survival after burn injuries.

Background: Autologous platelet-rich plasma (PRP) has been suggested to be effective for wound healing. However, evidence for its use in patients with acute and chronic wounds remains insufficient. The aims of this study were to comprehensively examine the effectiveness, synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair. Methods: Full-thickness wounds were made on the back of C57/BL6 mice. PRP or saline solution as a control was administered to the wound area. Wound healing rate, local inflammation, angiogenesis, re-epithelialization and collagen deposition were measured at days 3, 5, 7 and 14 after skin injury. The biological character of epidermal stem cells (ESCs), which reflect the potential for re-epithelialization, was further evaluated in vitro and in vivo. Results: PRP strongly improved skin wound healing, which was associated with regulation of local inflammation, enhancement of angiogenesis and re-epithelialization. PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β. An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1. Moreover, PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs, and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14. Conclusion: PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization. However, the underlying regulatory mechanism needs to be investigated in the future. Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.

Background: Hydrogels with tuneable mechanical properties are an attractive material platform for 3D bioprinting. Thus far, numerous studies have confirmed that the biophysical cues of hydrogels, such as stiffness, are known to have a profound impact on mesenchymal stem cell (MSC) differentiation; however, their differentiation potential within 3D-bioprinted hydrogels is not completely understood. Here, we propose a protocol for the exploration of how the stiffness of alginate–gelatin (Alg-Gel) composite hydrogels (the widely used bioink) affects the differentiation of MSCs in the presence or absence of differentiation inducing factors. Methods: Two types of Alg-Gel composite hydrogels (Young’s modulus: 50 kPa vs. 225 kPa) were bioprinted independently of porosity. Then, stiffness-induced biases towards adipogenic and osteogenic differentiation of the embedded MSCs were analysed by co-staining with alkaline phosphatase (ALP) and oil red O. The expression of specific markers at the gene level was detected after a 3-day culture. Results: Confocal microscopy indicated that all tested hydrogels supported MSC growth and viability during the culture period. Higher expression of adipogenic and osteogenic markers (ALP and lipoprotein lipase (LPL)) in stiffer 3D-bioprinted matrices demonstrated a more significant response of MSCs to stiffer hydrogels with respect to differentiation, which was more robust in differentiation-inducing medium. However, the LPL expression in stiffer 3D-bioprinted constructs was reduced at day 3 regardless of the presence of differentiation-inducing factors. Although MSCs embedded in softer hydrogels to some extent proceeded toward adipogenic and osteogenic lineages within a few days, their differentiation seemed to be slower and more limited. Interestingly, the hydrogel itself (without differentiation-inducing factors) exhibited a slight effect on whether MSCs differentiated towards an adipogenic or an osteogenic fate. Considering that the mechano-regulated protein Yes-associated protein (YAP) is involved in MSC fate decisions, we further found that inhibition of YAP significantly downregulated the expression of ALP and LPL in MSCs in stiffer constructs regardless of the induced growth factors present. Conclusions: These results demonstrate that the differentiation of MSCs in 3D-bioprinted matrices is dependent on hydrogel stiffness, which emphasizes the importance of biophysical cues as a determinant of cellular behaviour.

Background: There have been several attempts to define core outcome domains for use in research focused on adult burns. Some have been based in expert opinion, whilst others have used primary qualitative research to understand patients’ perspectives on outcomes. To date there has not been a systematic review of qualitative research in burns to identify a comprehensive list of patient-centred outcome domains. We therefore conducted a systematic review of qualitative research studies in adult burns. Methods: We searched multiple databases for English-language, peer-reviewed, qualitative research papers. We used search strategies devised using the SPIDER tool for qualitative synthesis. Our review utilized an iterative three-step approach: (1) outcome-focused coding; (2) development of descriptive accounts of outcome-relevant issues; and (3) revisiting studies and the broader theoretical literature in order to frame the review findings. Results: Forty-one articles were included. We categorized papers according to their primary focus. The category with the most papers was adaptation to life following burn injury (n = 13). We defined 19 outcome domains across the 41 articles: (1) sense of self; (2) emotional and psychological morbidity; (3) sensory; (4) scarring and scar characteristics; (5) impact on relationships; (6) mobility and range of joint motion; (7) work; (8) activities of daily living and self-care; (9) treatment burden; (10) engagement in activities; (11) wound healing and infection; (12) other physical manifestations; (13) financial impact; (14) impact on spouses and family members; (15) analgesia and side effects; (16) cognitive skills; (17) length of hospital stay; (18) access to healthcare; and (19) speech and communication. We suggest that sense of self is a core concern for patients that, to date, has not been clearly conceptualized in the burns outcome domain literature. Conclusions: This outcome domain framework identifies domains that are not covered in previous attempts to outline core outcome domains for adult burn research. It does so with reference to existing theoretical perspectives from the sociology and psychology of medicine. We propose that this framework can be used as a basis to ensure that outcome assessment is patient-centred. Sense of self requires further consideration as a core outcome domain.

Keloids are a fibroproliferative disorder that can result from a cutaneous injury to the reticular dermis. Recurrence rates as high as 100% have been reported following surgical excision alone. Consequently, a variety of post-surgical techniques have been employed to prevent keloid recurrence, including the use of radiation. Although numerous studies have shown post-excisional X-rays, electron beam, lasers and brachytherapy can reduce the rate of keloid recurrence, numerous inconsistencies, including a wide range of definitions for keloid recurrence, make it difficult to compare study outcomes. The review aims to examine the various means for defining keloid recurrence in clinical trials involving the use of radiation therapy. Searches of the Cochrane Library and PubMed were performed to identify the available information for post-surgical keloid recurrence following radiation therapy. Each identified study was reviewed for patient follow-up and criteria used to define keloid recurrence. The search results included clinical studies with external beam radiation, brachytherapy and superficial radiation therapy. Many studies did not include a definition of keloid recurrence, or defined recurrence only as the return of scar tissue. Other studies defined keloid recurrence based on patient self-assessment questionnaires, symptoms and scar elevation and changes in Kyoto Scar Scale, Japan Scar Workshop Scale and Vancouver Scar Scale scores. The results of this review indicate keloidectomy followed by radiation therapy provide satisfactory recurrence rates; however, clinical studies evaluating these treatments do not describe treatment outcomes or use different definitions of keloid recurrence. Consequently, recurrence rates vary widely, making comparisons across studies difficult. Keloid recurrence should be clearly defined using both objective and subjective measures.

Burn damage can lead to a state of immune dysregulation that facilitates the development of infections in patients. The most deleterious impact of this dysfunction is the loss of the skin’s natural protective barrier. Furthermore, the risk of infection is exacerbated by protracted hospitalization, urinary catheters, endotracheal intubation, inhalation injury, arterial lines and central venous access, among other mainstays of burn care. Currently, infections comprise the leading cause of mortality after major burn injuries, which highlights the improvements observed over the last 50 years in the care provided to burn victims. The need to implement the empirical selection of antibiotic therapy to treat multidrug-resistant bacteria may concomitantly lead to an overall pervasiveness of difficult-to-treat pathogens in burn centres, as well as the propagation of antimicrobial resistance and the ultimate dysregulation of a healthy microbiome. While preliminary studies are examining the variability and evolution of human and mice microbiota, both during the early and late phase burn injury, one must consider that abnormal microbiome conditions could influence the systemic inflammatory response. A better understanding of the changes in the post-burn microbiome might be useful to interpret the provenance and subsequent development of infections, as well as to come up with inferences on the prognosis of burn patients. This review aims to summarise the current findings describing the microbiological changes in different organs and systems of burn patients and how these alterations affect the risks of infections, complications, and, ultimately, healing.

An increased number of patients with skin wounds have been witnessed in the past decades. Among the various kinds of treatments for skin wounds, topical exogenous growth factors are indispensable and have been used in many countries. However, whether they have reliable effects remains controversial, and their application for skin wound treatment needs to be further standardized and optimized in terms of socio-economic considerations. Thus, the Chinese Burn Association developed this guideline indicating efficacy, application details, adverse reactions and precautions of five clinically common topical growth factors using the Grading of Recommendations Assessment Development and Evaluation method to promote the rational application of topical exogenous growth factors in skin wounds and to benefit more patients.

Background: Co-Cr-Mo alloy has been widely used in clinical implants because of its excellent mechanical and anti-corrosion properties, but there is an urgent need to address its disadvantages, such as implant-related infections and implant loosening. We synthesized Co-Cr-Mo-Cu (Co-Cu) alloys with different Cu contents to modify implant performance to be suitable as a bone-compatible implant material. Methods: Microstructure, phase content and mechanical properties of the Co-Cr-Mo alloy were characterized. Histological and immunohistochemical analyses were performed after implantation in rabbits. The experimental alloy was implanted on the lateral side of the lower tibial condyle and the tibial nodule. Results: Phase content and mechanical properties revealed that the crystallographic structure and wear resistance were changed. Experimental implantation results demonstrated that osteogenic capability was markedly enhanced, ascribed to the excellent antibacterial and osseointegration capacities of Cu phases, and with the release of Cu ions. In particular, Co-Cu alloy containing 2 wt% Cu exhibited the best osteogenic performance among all samples. Conclusions: The results indicated that osteogenic performance of the Co-Cr-Mo alloy could be enhanced by adding Cu. In particular, the Co-2Cu alloy exhibited the best properties according to both immunohistochemical and histological analyses. Our study not only provides deep insight into the osteogenic effect of Cu but presents a new Co-Cu alloy for clinical implants.

Wound healing, tissue repair and regenerative medicine are in great demand, and great achievements in these fields have been made. In recent years, many of these successes have benefited patients, especially in the field of chronic skin wounds. However, perfect tissue repair and regeneration of damaged tissues and organs are still great challenges in the management of trauma and diseases. In this paper, the main achievements in wound healing, tissue repair and regeneration in China are reviewed and the establishment of wound healing centers and new technology application in improving wound healing quality in patients in China is highlighted.

There is little research that focuses on the relationship between the gut, metabolism, nutritional support and COVID-19. As a group of Chinese physicians, nutritionists and scientists working on the frontline treating COVID-19 patients, we aim to integrate our experiences and the current clinical evidence to address this pressing issue in this article. Based on our clinical observations and available evidence, we recommend the following practice. Firstly, the Nutritional Risk Screening 2002 tool should be used routinely and periodically; for patients with a score ≥3, oral nutritional supplements should be given immediately. Secondly, for patients receiving the antiviral agents lopinavir/ritonavir, gastrointestinal side effects should be monitored for and timely intervention provided. Thirdly, for feeding, the enteral route should be the first choice. In patients undergoing mechanical ventilation, establishing a jejunal route as early as possible can guarantee the feeding target being achieved if gastric dilatation occurs. Fourthly, we suggest a permissive underfeeding strategy for severe/critical patients admitted to the intensive care unit during the first week of admission, with the energy target no more than 20 kcal/kg/day (for those on mechanical ventilation, this target may be lowered to 10–15 kcal/kg/day) and the protein target around 1.0–1.2 g/kg/day. If the inflammatory condition is significantly alleviated, the energy target may be gradually increased to 25–30 kcal/kg/day and the protein target to 1.2–1.5 g/kg/day. Fifthly, supplemental parenteral nutrition should be used with caution. Lastly, omega-3 fatty acids may be used as immunoregulators, intravenous administration of omega-3 fatty emulsion (10 g/day) at an early stage may help to reduce the inflammatory reaction.