The burden of skin and subcutaneous diseases: findings from the global burden of disease study 2019.

Background: The small number of existing integrative studies on the global distribution and burden of all types of skin and subcutaneous diseases hinders relevant comparisons. Objective: This study aimed to determine the latest distribution, epidemiological differences, and factors potentially influencing each skin and subcutaneous disease and the policy implications. Methods: Data on the skin and subcutaneous diseases were obtained from the Global Burden of Disease Study 2019. The incidence, disability-adjusted life years (DALYs), and deaths due to skin and subcutaneous diseases in 204 countries and regions from 1990 to 2019 were analyzed and stratified by sex, age, geographical location, and sociodemographic index (SDI). The annual age-standardized rate of change in the incidence was obtained to evaluate temporal trends. Results: Of 4,859,267,654 (95% uncertainty interval [UI], 4,680,693,440-5,060,498,767) new skin and subcutaneous disease cases that were identified, most were fungal (34.0%) and bacterial (23.0%) skin diseases, which accounted for 98,522 (95% UI 75,116-123,949) deaths. The burden of skin and subcutaneous diseases measured in DALYs was 42,883,695.48 (95%UI, 28,626,691.71-63,438,210.22) in 2019, 5.26% of which were years of life lost, and 94.74% of which were years lived with disability. The highest number of new cases and deaths from skin and subcutaneous diseases was in South Asia. Globally, most new cases were in the 0-4-year age group, with skin and subcutaneous disease incidence slightly higher in men than in women. Conclusion: Fungal infections are major contributors to skin and subcutaneous diseases worldwide. Low-middle SDI states had the highest burden of skin and subcutaneous diseases, and this burden has increased globally. Targeted and effective management strategies based on the distribution characteristics of each country are, thus, required to reduce the burden of skin and subcutaneous diseases.

Single-cell analysis reveals melanocytes may promote inflammation in chronic wounds through cathepsin G.

During acute wound (AW) healing, a series of proper communications will occur between different epidermal cells at precise temporal stages to restore the integrity of the skin. However, it is still unclear what variation happened in epidermal cell interaction in the chronic wound environment. To provide new insights into chronic wound healing, we reconstructed the variations in the epidermal cell-cell communication network that occur in chronic wound healing via single-cell RNA-seq (scRNA-seq) data analysis. We found that the intricate cellular and molecular interactions increased in pressure ulcer (PU) compared to AW, especially the PARs signaling pathways were significantly upregulated. It shows that the PARs signaling pathways' main source was melanocytes and the CTSG-F2RL1 ligand-receptor pairs were its main contributor. Cathepsin G (CatG or CTSG) is a serine protease mainly with trypsin- and chymotrypsin-like specificity. It is synthesized and secreted by some immune or non-immune cells. Whereas, it has not been reported that melanocytes can synthesize and secrete the CTSG. F2R Like Trypsin Receptor 1 (F2RL1) is a member of proteinase-activated receptors (PARs) that are irreversibly activated by proteolytic cleavage and its stimulation can promote inflammation and inflammatory cell infiltration. In this study, we found that melanocytes increased in pressure ulcers, melanocytes can synthesize and secrete the CTSG and may promote inflammation in chronic wounds through CTSG-F2RL1 pairs, which may be a novel potential target and a therapeutic strategy in the treatment of chronic wounds.

The epidemiological characteristic and trends of burns globally.

BACKGROUND: Burns is a type of injury, caused by unintentional exposure to substances of high temperature, including hot liquid, solid, and objects radiating heat energy, placing a high burden not only on patients' families but also on national healthcare systems globally. It is difficult for policymakers and clinicians to formulate targeted management strategies for burns because data on current epidemiological patterns worldwide are lacking. METHODS: Data on burns were obtained from the Global Burden of Disease (GBD) 2019 Study. The incidence, disability-adjusted life years (DALYs), and deaths of burns in 204 countries and regions from 1990 to 2019 were calculated and stratified by sex, age, geographical location, and sociodemographic index (SDI). The estimated annual percentage change (EAPC) of incidence, DALYs, and deaths was calculated to evaluate the temporal trends. All analyses were performed using R software, version 4.1.1, with 2-sided P-values < .05 indicating a statistically significant difference. RESULTS: A total of 8,378,122 new cases (95% UI, 6,531,887-10,363,109cases) of burns were identified globally in 2019, which is almost evenly split between men and women, and most of the new cases were concentrated in the 10-19-year age group. Besides, burns account for 111,292 deaths (95% UI, 132,392-88,188) globally in 2019, most of which were concentrated in those aged 1-4 years. The burden of burns measured in DALYs was 7,460,448.65 (95% UI, 5,794,505.89-9,478,717.81) in 2019, of which 67% and 33% could be attributed to YLLs and YLDs, respectively. The EAPC of incidence, DALYs, and deaths were negative, the age-standardized rate (ASR) of incidence, DALYs, and deaths were considered to be decreasing in most of the regions, and the EAPCs were negatively correlated with SDI levels, universal health coverage (UHC), and gross domestic product (GDP). CONCLUSION: Globally, the age-standardized rates of burn incidence, DALYs, and mortality, as well as the number of burn DALYs and death cases will continuously decrease, but the number of new burn cases has an increasing tendency globally. In addition, the EAPCs of burns in incidence, DALYs, and deaths indicated that the burden of burns was considered to be decreasing in most of the regions. And from the relationship of EAPCs with SDI, UHC index, and GDP, indicate that prevention burns not only depend on health spending per capita but also depend on the education level per capita and healthcare system performance, but it does not mean higher health spending corresponds to higher UHC index, which needs high efficiency of translating health spending into individuals health gains.

CT-Angiography-Based Outcome Prediction on Diabetic Foot Ulcer Patients: A Statistical Learning Approach.

The purpose of our study is to predict the occurrence and prognosis of diabetic foot ulcers (DFUs) by clinical and lower extremity computed tomography angiography (CTA) data of patients using the artificial neural networks (ANN) model. DFU is a common complication of diabetes that severely affects the quality of life of patients, leading to amputation and even death. There are a lack of valid predictive techniques for the prognosis of DFU. In clinical practice, the use of scales alone has a large subjective component, leading to significant bias and heterogeneity. Currently, there is a lack of evidence-based support for patients to develop clinical strategies before reaching end-stage outcomes. The present study provides a novel technical tool for predicting the prognosis of DFU. After screening the data, 203 patients with diabetic foot ulcers (DFUs) were analyzed and divided into two subgroups based on their Wagner Score (138 patients in the low Wagner Score group and 65 patients in the high Wagner Score group). Based on clinical and lower extremity CTA data, 10 predictive factors were selected for inclusion in the model. The total dataset was randomly divided into the training sample, testing sample and holdout sample in ratio of 3:1:1. After the training sample and testing sample developing the ANN model, the holdout sample was utilized to assess the accuracy of the model. ANN model analysis shows that the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of the overall ANN model were 92.3%, 93.5%, 87.0%, 94.2% and 0.955, respectively. We observed that the proposed model performed superbly on the prediction of DFU with a 91.6% accuracy. Evaluated with the holdout sample, the model accuracy, sensitivity, specificity, PPV and NPV were 88.9%, 90.0%, 88.5%, 75.0% and 95.8%, respectively. By contrast, the logistic regression model was inferior to the ANN model. The ANN model can accurately and reliably predict the occurrence and prognosis of a DFU according to clinical and lower extremity CTA data. We provided clinicians with a novel technical tool to develop clinical strategies before end-stage outcomes.

Global, Regional, and National Levels and Trends in the Burden of Pressure Ulcer from 1990 to 2019: A Systematic Analysis for the Global Burden of Disease 2019.

Pressure ulcer (PU) is a type of chronic ulcer, placing a high burden not only on patients' families but also on national healthcare systems globally. To determine the level, trends, and burden of PU worldwide and to provide an essential foundation for building targeted public policies on PUs at the national, regional, and global levels, data on PU were obtained from the Global Burden of Disease (GBD) 2019 Study. The incidence, disability-adjusted life years (DALYs), and deaths of PUs in 204 countries and regions from 1990 to 2019 were calculated and stratified by sex, age, geographical location, and sociodemographic index (SDI). The estimated annual percentage change (EAPC) of incidence, DALYs, and deaths was calculated to evaluate the temporal trends. A total of 3,170,796 new cases (95% uncertainty interval (UI), 3,499,729-2,875,433 cases) of PU were identified globally in 2019, more than 55% of which were among male individuals, and most of the new cases were concentrated in those 75-90 years of age. The burden of PU measured in DALYs was 481 423 (95% UI, 583 429-374 334) in 2019, 73% and 27% of which could be attributed to years of life lost (YLLs) and years lived with disability (YLDs), respectively. The burden increased gradually from 1990 to 2019 (from 267 846 [360 562-211 024] to 481 423 [95% UI, 583 429-374 334]). A total of 24 389 deaths were attributed to PU (95% UI, 31 260.82-17 299). The EAPC of incidence, DALYs, and deaths were negative in most regions, the age-standardized rate (ASR) of incidence, DALYs, and deaths were considered to be decreasing in most of the regions, and the EAPCs were negatively correlated with the SDI levels, universal health coverage (UHC), and gross domestic product (GDP), which shows that the ASRs of PU decreased as the economy developed and countries' healthcare system performances improved.

Pyridoxamine ameliorates methylglyoxal-induced macrophage dysfunction to facilitate tissue repair in diabetic wounds.

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound formed during hyperglycaemia. MGO combines with proteins to form advanced glycation end products (AGEs), leading to cellular dysfunction and organ damage. In type 2 diabetes mellitus (T2DM), the higher the plasma MGO concentration, the higher the lower extremity amputation rate. Here, we aimed to identify the mechanisms of MGO-induced dysfunction. We observed that the accumulation of MGO-derived AGEs in human diabetic wounds increased, whereas the expression of glyoxalase 1 (GLO1), a key metabolic enzyme of MGO, decreased. We show for the first time that topical application of pyridoxamine (PM), a natural vitamin B6 analogue, reduced the accumulation of MGO-derived AGEs in the wound tissue of type-2 diabetic mice, promoted the influx of macrophages in the early stage of tissue repair, improved the dysfunctional inflammatory response, and accelerated wound healing. In vitro, MGO damaged the phagocytic functions of M1-like macrophages induced by lipopolysaccharide (LPS), but not those of M0-like macrophages induced by PMA or of M2-like macrophages induced by interleukins 4 (IL-4) and 13 (IL-13); the impaired phagocytosis of M1-like macrophages was rescued by PM administration. These findings suggest that the increase in MGO metabolism in vivo might contribute to macrophage dysfunction, thereby affecting wound healing. Our results indicate that PM may be a novel therapeutic approach for treating diabetic wounds. MGO forms protein adducts that cause macrophage dysfunction. These adducts cause cell and organ dysfunction that is common in diabetes. Pyridoxamine scavenges MGO to ameliorate this dysfunction, promoting wound healing. Pyridoxamine could be used therapeutically to treat non-healing diabetic wounds.

The application value of computed tomography and magnetic resonance imaging sinography/fistulography in evaluating chronic wounds: a prospective study.

BACKGROUND: Chronic wounds are a worldwide health problem, with traditional imaging techniques failing in their accurate evaluation. Therefore, an effective imaging evaluation method is needed for the diagnosis and treatment or chronic wounds. This study is to investigate the application value of computed tomography (CT) and magnetic resonance imaging (MRI) sinography/fistulography in assessing the morphology and deep features of chronic wounds. METHODS: We prospectively enrolled 43 chronic wounds patients who received both CT and MRI sinography/fistulography. The morphology and deep features of chronic wound on CT and MRI images were independently evaluated by 2 experienced radiologists. Kappa value and intraclass correlation coefficient (ICC) were calculated to evaluate the interobserver agreement and the consistency between CT and MRI sinography/fistulography in assessing the shape, number of branches, and involvement of body cavity and bones of chronic wounds. RESULTS: There were substantial to almost perfect interobserver agreements for both CT and MRI sinography/fistulography in evaluating the morphology and deep features of chronic wounds. The consistency between CT and MRI was almost perfect for the 2 readers in evaluating the shape (reader 1, kappa value =1.000; reader 2, kappa value =0.932) and the number of branches [reader 1, ICC =0.951 (95% confidence interval: 0.909-0.973, P<0.001); reader 2, ICC =0.874 (95% confidence interval: 0.768-0.932, P<0.001)], and substantial to almost perfect when evaluating the involvement of body cavity (reader 1, kappa value =0.728; reader 2, kappa value =0.775) and bones (reader 1, kappa value =0.659; reader 2, kappa value =0.860). CONCLUSIONS: There was good interobserver agreement and consistency between CT and MRI sinography/fistulography in evaluating the morphology and deep features of chronic wounds.

[Application value of flexible endoscopy and rigid endoscopy in the clinical examination of chronic sinus tract wounds with different shapes].

Objective: To explore the application value of flexible endoscopy and rigid endoscopy in the clinical examination of chronic sinus tract wounds with different shapes. Methods: A retrospective observational study was conducted. From January 1 to December 23, 2019, a total of 46 patients with chronic sinus tract wounds, who met the inclusion criteria were admitted to the Wound Healing Center of Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, including 23 males and 23 females, aged 18-81 (48±21) years. On admission, computer tomography (CT) imaging and three-dimensional reconstruction were performed to examine the shapes of wound sinus tract and classify the wounds, with the lengths of wound sinus tract by CT imaging examination (hereinafter referred to as reference lengths) recorded. The lengths of wound sinus tract were examined and measured by rigid endoscopy and flexible endoscopy. The wounds with and without obviously curved sinus tract were classified into curve group and linear group respectively, and the deviation rates between the lengths of wound sinus tract measured by flexible endoscopy or rigid endoscopy and the reference lengths (hereinafter referred to as deviation rates of lengths) in each group were calculated. The difference between the deviation rates of lengths examined by flexible endoscopy and rigid endoscopy and the differences between the above two and the deviation rate of reference lengths (0) in each group were compared. Data were statistically analyzed with paired sample t test and Wilcoxon signed rank sum test. Results: CT imaging and three-dimensional reconstruction showed that there were 4 types of wound sinus tract, including tubular (36/46), lamellar (4/46), club-mallet (4/46), and irregular (2/46) shape. Tubular wounds were further divided into type I (23/36), type L (4/36), and type Y (9/36). Wounds with type I tubular, lamellar, and club-mallet sinus tract were classified into linear group (31/46), while those with type Y tubular, type L tubular, and irregular sinus tract were classified into curve group (15/46). In linear group, the deviation rates of lengths examined and measured by rigid endoscopy and flexible endoscopy were 0. In curve group, the deviation rate of lengths examined and measured by flexible endoscopy was 0 (0, 0.58%), which was significantly lower than 41.18% (31.68%, 48.41%) examined and measured by rigid endoscopy, Z=-3.408, P<0.01; the deviation rate of lengths examined and measured by rigid endoscopy (40±19)% was significantly higher than the deviation rate of reference lengths (t=8.343, P<0.01), while the deviation rate of the lengths examined and measured by flexible endoscopy was similar to the deviation rate of reference lengths (Z=-1.342, P>0.05). Conclusions: Compared with rigid endoscopy, flexible endoscopy can observe the internal characteristics of chronic sinus tract wounds in a wider range in the clinical examination of this kind of wound, especially for the exploration of curved chronic sinus tract wounds. The promotion of this method will be conducive to the diagnosis and treatment of chronic sinus tract wounds.