Morbidity in Patients with Nasopharyngeal Carcinoma and Radiation-Induced Skin Lesions: Cause, Risk Factors, and Dermatitis Evolution and Severity.

OBJECTIVE: Radiation-induced skin injuries such as lesions (RSLs) and dermatitis are the most common complication during radiotherapy (RT) for nasopharyngeal carcinoma, but little is known about risk factors unique to oncology. This study sought a greater understanding of these risk factors to stratify patients based on risk and guide clinical decision-making. METHODS: Investigators analyzed the data of 864 consecutive patients referred to the RT center of the Southern Theater General Hospital for a new RSL from 2013 to 2019. These patients were followed up for an average of approximately 16 months until their death or March 30, 2020, whichever came first. Multivariate logistic regression analysis and Cox proportional hazards model were used to identify predictors of grade 3 or 4 dermatitis. RESULTS: The main causes of treatment interruption included dermatitis and oral mucositis. Significant patient-specific risk factors for RSLs included current smoking, current drinking, and lower Karnofsky Performance Scale score and significant procedure-specific risk factors included receiving intensity-modulated radiation therapy (IMRT), hyperfractionated RT, induction chemotherapy, multicycle chemotherapy, and taxol- and cisplatin-based drugs. The three factors that independently predicted risk of RSL were IMRT, lower Karnofsky Performance Scale score, and multicycle chemotherapy. Comparing predictive factors among patients with severe RSL revealed that patients who received IMRT were more likely to develop grade 3 or 4 dermatitis. CONCLUSIONS: Oncology providers should note that IMRT is an aggressive technique with a trend toward increased RSL. Providers should pay special attention to adverse effects to skin in patients with nasopharyngeal carcinoma.

Radiation-induced acute injury of intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy in induction chemotherapy followed by concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a prospective cohort study.

To address whether the addition of intensity-modulated radiotherapy (IMRT) compared to three-dimensional conformal radiotherapy (3D-CRT) aggravate radiation-induced acute injury of locoregionally advanced nasopharyngeal carcinoma (LANPC) patients with induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT). We conducted a prospective study of 182 patients in the stage III to IVb with biopsy-proven nonmetastatic LANPC who newly underwent radiotherapy and sequentially received IC, followed by CCRT at our institution. Occurring time of radiation-induced toxicities were estimated and compared using the Kaplan-Meier method and Log-rank test. The most severe acute toxicities included oral mucositis in 97.25% and dermatitis in 90.11%. Subset analysis revealed that Grade 3-4 acute dermatitis were significantly higher in the IMRT than 3D-CRT. Oral mucositis and dermatitis were the earliest occurrence of acute injuries (2 years: 60.44% and 17.58%). Patients in IMRT group achieved significantly lower risk of bone marrow toxicity, but higher risk of leukopenia and gastrointestinal injury. Multivariate analyses also demonstrated that IMRT, female gender and hepatitis were the independent prognostic factors for bone marrow toxicity. In a combined regimen of IC followed by CCRT for the treatment of LANPC, IMRT seems to be an aggressive technique with a trend towards increased gastrointestinal and hematological toxicities, but decreased bone marrow toxicity than those treated with 3D-CRT. This study provides a comprehensive summary of prospective evidence reporting the side effects in the management of LANPC patients. We quantify the occurrence risks of chemoradiotherapy-induced acute injuries through analysis of time-to-event.

A Rule of Thumb for Evaluating Surface Areas of Chronic Wounds.

BACKGROUND: Rapid estimation of the area of chronic wounds is clinically important. A simple method using the thumb was investigated for universal physical measurement, particularly of small and multiple wounds; the thumb surface area (TSA) was then compared with the total body surface area (TBSA). METHODS: A cross-sectional observational study and random sampling were used to obtain the characteristics of 343 participants. Data related to handprint surface area of the thumb and palm were collected using a scanner and laptop and assessed using image software. The TSA as a percentage of TBSA was confirmed based on the traditional rule that regards palmar surface area as 1% of TBSA. Information on factors potentially influencing measurement was gathered with questionnaires to analyze correlations. RESULTS: The left and right TSAs were on average 4.27% and 4.28%, respectively, of the palmar surface area for all participants. Multiple linear regression analysis found that male and older participants had higher TSA:TBSA proportions (sex, P = .0020; age, P < .0001). The TSA:TBSA proportion increased by age for both males (by age group, 0.0418%, 0.0426%, 0.0432%, and 0.0460%, respectively) and females (0.0400%, 0.0409%, 0.0427%, and 0.0430%, respectively). CONCLUSIONS: Thumb size is relatively stable in relation to TBSA, lending itself to a universal method for estimating the size of chronic wounds as a percentage of TBSA. It therefore represents a convenient physical measurement for assessing the area of burns and other wounds.

A composite hydrogel with co-delivery of antimicrobial peptides and platelet-rich plasma to enhance healing of infected wounds in diabetes.

Diabetic wound healing remains a major challenge due to its vulnerability to bacterial infection, as well as the less vascularization and prolonged inflammatory phase. In this study, we developed a hydrogel system for the treatment of chronic infected wounds, which can regulate inflammatory (through the use of antimicrobial peptides) and enhance collagen deposition and angiogenesis (through the addition of platelet-rich plasma (PRP)). Based on the formation of Schiff base linkage, the ODEX/HA-AMP/PRP hydrogel was prepared by mixing oxidized dextran (ODEX), antimicrobial peptide-modified hyaluronic acid (HA-AMP) and PRP under physiological conditions, which exhibited obvious inhibition zones against three pathogenic bacterial strains (E. coli, S. aureus and P. aeruginosa) and slow release ability of antimicrobials and growth factors. Moreover, CCK-8, live/dead fluorescent staining and scratch test confirmed that ODEX/HA-AMP/PRP hydrogel could facilitate the proliferation and migration of L929 fibroblast cells. More importantly, in vivo experiments further demonstrated that the prepared hydrogels could significantly improve wound healing in a diabetic mouse infection by regulating inflammation, accelerating collagen deposition and angiogenesis. In addition, prepared hydrogel showed a significant antibacterial activity against S. aureus and P. aeruginosa, inhibited pro-inflammatory factors (TNF-α, IL-1ß and IL-6), enhanced anti-inflammatory factors (TGF-ß1) and vascular endothelial growth factor (VEGF) production. The findings of this study suggested that the composite hydrogel with AMP and PRP controlled release ability could be used as a promising candidate for chronic wound healing and infection-related wound healing.

Co-administration of platelet-rich plasma and small intestinal submucosa is more beneficial than their individual use in promoting acute skin wound healing.

Background: Acute skin wounds may compromise the skin barrier, posing a risk of infection. Small intestinal submucosa (SIS) is widely used to treat acute and chronic wounds. However, the efficacy of SIS to accelerate wound healing still needs to be improved to meet clinical demands. To tackle this problem, platelet-rich plasma (PRP) is used due to its potency to promote proliferation, migration and adhesion of target cells. In this study, we applied PRP and SIS to skin wounds to explore their effects on wound healing by evaluating re-epithelialization, collagen production, angiogenesis and the inflammatory response. Methods: A 1 × 1-cm full-thickness skin defect was established in mice. Sixty mice were divided into four treatment groups: PRP + SIS, PRP, SIS and control. On days 3, 5, 7, 10 and 14 post-surgery, tissue specimens were harvested. Haematoxylin and eosin, Masson's trichrome, immunohistochemical and immunofluorescence double staining were used to visualize epidermal thickness, collagen and vascular regeneration and inflammation. Results: Wound contraction in the PRP and PRP + SIS groups was significantly greater, compared with the other groups, on days 3 and 5 post-surgery. A histological analysis showed higher collagen expression in the PRP and PRP + SIS groups on day 7, which was associated with a thicker epidermal layer on day 14. In addition, immunohistochemical staining showed that CD31-positive blood vessels and vascular endothelial growth factor expression in the PRP + SIS and PRP groups were significantly higher, compared with the control group. Furthermore, immunofluorescence double staining showed that the number of M1 and M2 macrophages in the PRP + SIS and PRP groups was higher, compared with the control and SIS groups alone, on day 3. However, on day 7, the number of M1 macrophages dramatically decreased in the PRP + SIS and PRP groups. The ratio of M2 to M1 macrophages in the PRP + SIS and PRP groups was 3.97 and 2.93 times that of the control group and 4.56 and 3.37 times that of the SIS group, respectively. Conclusion: Co-administration of SIS and PRP has a better effect on promoting angiogenesis, re-epithelialization and collagen regeneration in managing acute wound healing than either agent alone.

Human Salivary Histatin-1 Is More Efficacious in Promoting Acute Skin Wound Healing Than Acellular Dermal Matrix Paste.

A rapid wound healing is beneficial for not only recovering esthetics but also reducing pain, complications and healthcare burdens. For such a purpose, continuous efforts have been taken to develop viable dressing material. Acellular dermal matrix (ADM) paste has been used to repair burn wounds and is shown to promote angiogenesis as well as fibroblast attachment and migration. However, its efficacy still needs to be significantly improved to meet clinical demands for accelerating acute skin wound healing. To approach this problem, we studied the added value of a human salivary peptide - Histatin 1 (Hst1). Hst1 was chosen because of its potency to promote the adhesion, spreading, migration, metabolic activity and cell-cell junction of major skin cells and endothelial cells. In this study, we hypothesized that ADM paste and Hst1 showed a better effect on the healing of surgically created acute skin wounds in mice since ADM paste may act as a slow release system for Hst1. Our results showed that the healing efficacy of 10 µM topically administrated Hst1 was significantly higher compared to the control (no Hst1, no ADM) from day 3 to day 10 post-surgery. In contrast, ADM alone failed in our system at all time points. Also, the combination of ADM paste and Hst1 did not show a better effect on percentage of wound healing. Histological analysis showed that 10 µM Hst1 was associated with maximal thickness of newly formed epidermal layer on day 7 as well as the largest collagen area on day 14. In addition, immunohistochemical staining showed that the number of CD31-positive blood vessels in the group of 10 µM Hst1 was 2.3 times compared to the control. The vascular endothelial growth factor (VEGF) expression in the groups of 10 µM Hst1 group and ADM + 10 µM Hst1 group was significantly higher compared with the control group. Furthermore, 10 µM Hst1 group was associated with significantly lower levels of CD68-positive macrophage number, interleukin-1ß (IL-1ß) expression and C-reactive protein (CRP) expression than those of the other groups (control, ADM alone and ADM + 10 µM Hst1). In contrast, ADM was only associated with significantly lower CD68-positive macrophage number and IL-1ß expression in comparison with the control. The co-administration of Hst1 and ADM paste did not yield more beneficial effects than Hst1 alone. In conclusion, the topically administrated of 10 µM Hst1 could be a promising alternative dressing in managing acute wound healing.

Prevalence of Chronic Skin Wounds and Their Risk Factors in an Inpatient Hospital Setting in Northern China.

OBJECTIVE: To gain insight into the magnitude of the problem of chronic skin wounds in a hospital in northern China. METHODS: Researchers conducted a retrospective analysis of electronic health records of cases and controls, including 1,977 patients with chronic skin wounds admitted to the hospital's medical wards over 5 years. Multiple logistic regression was used to establish factors correlating with the development of chronic wounds. RESULTS: The total prevalence of chronic wounds increased over the study period, and the occurrence of these wounds was significantly correlated with male sex, married status, unemployment, autumn season, and older age. The primary causes of chronic wounds were infection and diabetic ulcer. There were proportionally more wounds secondary to disease than traumatic wounds. The mean duration of hospitalization for patients with wounds was 13 days, and patients were readmitted an average of 10 times. CONCLUSIONS: With the rapidly aging population in China, disability and chronic wounds are significant problems. Reducing hospital lengths of stay and readmissions remains a challenge. Palliative care may be appropriate for the management of some chronic wounds to prevent and treat further complications. Establishing funding guarantees and the reasonable allocation of health resources is required.

Antibiotic-loaded chitosan-gelatin scaffolds for infected seawater immersion wound healing.

Skin damaged during sea battles is vulnerable to seawater immersion and bacterial infection. Scaffolds with effective biological function are highly desired for treatment of naval combat wound injuries. Herein, we prepared composite scaffolds of CS/GEL/GMs-CIP. The chitosan (CS) and gelatin (GEL) were cross-linked by genipin as matrix, and then gelatin microspheres loading ciprofloxacin hydrochloride (GMs-CIP) were add. From in vitro characterization results, CS/GEL/GMs-CIP had high water absorption ability, proper porosity, satisfactory fracture resistance, and flexibility. Furthermore, CS/GEL/GMs-CIP composite scaffold had excellent biocompatibility. Antibacterial experiments confirmed that CS/GEL/GMs-CIP had a significant inhibitory effect on E. coli, S. aureus and P. aeruginosa. The in vivo wound healing was evaluated using animal wound infection model of seawater immersion, and it was observed that the prepared composite scaffolds accelerated wound healing, reepithelialization, collagen deposition. Further analysis of wound tissue indicated that the expression of anti-inflammatory factor (TGF-ß1) was up-regulated, but the serum endotoxin levels and expression of pro-inflammatory factor (TNF-a, IL-6, and IL-1ß) were down-regulated. In summary, we believe that CS/GEL/GMs-CIP composite scaffold may serve as a promising multifunctional dressing for healing with open trauma wound infections and wound with seawater immersion.

Changes in Foot Skin Microbiome of Patients with Diabetes Mellitus Using High-Throughput 16S rRNA Gene Sequencing: A Case Control Study from a Single Center.

BACKGROUND Worldwide, the treatment of complications associated with type 2 diabetes mellitus, including diabetic foot ulcer (DFU), results in an economic burden for patients and healthcare systems. This study aimed to use high-throughput 16S rRNA gene sequencing to investigate the changes in foot skin microbiome of patients with diabetes mellitus from a single center in China. MATERIAL AND METHODS Fifty-two participants were divided into 4 study groups: healthy controls (n=13); patients with short-term diabetes (<2 years; n=13); patients with intermediate-term diabetes (5-8 years; n=13); and patients with long-term diabetes (>10 years; n=13). Swabs were analyzed from the intact skin of the foot arch using high-throughput 16S ribosomal RNA sequencing. RESULTS Microbiome phylogenic diversity varied significantly between the study groups (whole tree, P<0.01; Chao1, P<0.01), but were similar within the same group. The findings were supported by non-parametric multidimensional scaling (stress=0.12) and principal component analysis (principal component 1, 8.38%; principal component 2, 5.28%). In patients with diabetes mellitus, the dominant skin microbial phyla were Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. CONCLUSIONS High-throughput 16S rRNA gene sequencing showed dynamic changes in the skin microbiome from the foot during the progression of diabetes mellitus. These findings support the importance of understanding the role of the skin microbiota in the pathogenesis of DFU.

Human-microorganism mutualism theory: Possible mechanisms for the delayed chronic wound healing process.

Skin microbial flora was believed to can implicate skin health, and many recent reports point out a close linkage between the dysbiosis of the microbiome with the disease. Changes of microbiota, including diversity, species, and abundance, have been demonstrated in disease states, and it was believed the changes may cause infection and chronicity of the debilitating wounds. And it was been found a reverse of the dysbiosis after the effective treatment, but it failed to find a positive effect of antibiotic therapy on skin disease without significant clinical infection. The microbiomes were compared to the 'second gene reservoir', and indicated that their co-existing with the human being is a result of co-evolution. The current studies have shown that the microbial community on the skin surface should have an ideal optimal state, which can effectively regulate the immune tolerance and help to avoid the invasion of external pathogenic bacteria, then the body can be in a relatively healthy state. In this paper, we hypothesized that failing to maintain the harmonious relationship between microbes and human beings is the reason we suffering from most skin diseases, including chronic non-healing wounds. Thus, the dysbiosis of skin microbiota theory can help us better understand the mechanism of wound formation and problems encountered in wound treatment.

Nonselective alpha-/beta- AR antagonists can inhibit pericyte proliferation, migration, and secretion in vitro.

It has been reported that the beta-adrenergic receptor blocker (propranolol) and the a-adrenergic receptor (AR) blocker (phentolamine) both can inhibit human endothelial cell (EC) angiogenesis in vitro. However, it is unknown whether this inhibition also acts on pericytes. The present study aimed to determine how pericytes react to treatment with an a-/ß- AR blocker. In the study, cell proliferation assays and scratch assay were performed to assess the effect of phentolamine or propranolol on cell proliferation and migration. Western blot and ELISA were employed to determine changes in VEGF-A and Ang-1 expression levels. The results indicated that the nonselective a-/ß- AR blocker inhibited the proliferation, migration, and secretion of pericytes. The use of the nonselective a-/ß- AR blocker might have an impact on vascularization and vascular maturation. Our research suggests the rational use of nonselective a-/ß- AR blockers to treat angiogenesis-dependent diseases.

Preparation of Antimicrobial Hyaluronic Acid/Quaternized Chitosan Hydrogels for the Promotion of Seawater-Immersion Wound Healing.

Wound immersion in seawater with high salt, high sodium, and a high abundance of pathogenic bacteria, especially gram-negative bacteria, can cause serious infections and difficulties in wound repair. The present study aimed to prepare a composite hydrogel composed of hyaluronic acid (HA) and quaternized chitosan (QCS) that may promote wound healing of seawater-immersed wounds and prevent bacterial infection. Based on dynamic Schiff base linkage, hydrogel was prepared by mixing oxidized hyaluronic acid (OHA) and hyaluronic acid-hydrazide (HA-ADH) under physiological conditions. With the addition of quaternized chitosan, oxidized hyaluronic acid/hyaluronic acid-hydrazide/quaternized chitosan (OHA/HA-ADH/O-HACC and OHA/HA-ADH/N-HACC) composite hydrogels with good swelling properties and mechanical properties, appropriate water vapor transmission rates (WVTR), and excellent stability were prepared. The biocompatibility of the hydrogels was demonstrated by in vitro fibroblast L929 cell culture study. The results of in vitro and in vivo studies revealed that the prepared antibacterial hydrogels could largely inhibit bacterial growth. The in vivo study further demonstrated that the antibacterial hydrogels exhibited high repair efficiencies in a seawater-immersed wound defect model. In addition, the antibacterial hydrogels decreased pro-inflammatory factors (TNF-α, IL-1ß, and IL-6) but enhanced anti-inflammatory factors (TGF-ß1) in wound. This work indicates that the prepared antibacterial composite hydrogels have great potential in chronic wound healing applications, such as severe wound cure and treatment of open trauma infections.