Pedal medial arterial calcification in diabetic foot ulcers: A significant risk factor of amputation and mortality.

AIMS: Pedal medial arterial calcification (MAC) is frequently observed in individuals with diabetic foot ulcers (DFUs). However, the impact of pedal MAC on individuals with DFUs remains uncertain. The main aim of this study was to evaluate the association between pedal MAC with amputation and mortality outcomes. METHODS: A prospective, observational cohort study was conducted at West China Hospital from January 2012 to December 2021. Logistic regression analyses, Kaplan-Meier survival method, and Cox proportional hazards models were employed to evaluate the relationship between pedal MAC and amputation as well as mortality. RESULTS: A total of 979 patients were enrolled in the study. Peripheral artery disease (PAD) was observed in 53% of patients with DFUs, and pedal MAC was found in 8%. Over a median follow-up of 46 (23-72) months, foot amputation was performed on 190 patients, and mortality occurred in 246 patients. Pedal MAC showed a significant association with amputation both in unadjusted analysis (odds ratio [OR] = 2.98, 95% confidence interval [CI] = 1.86-4.76, p < .001) and after adjusting sex, age, albumin levels, hemoglobin levels, and diabetic retinopathy status (OR 2.29, 95% CI 1.33-3.93, p = .003). The risk of amputation was found to be twofold higher in individuals with PAD and pedal MAC compared to those with PAD alone (OR 2.05, 95% CI 1.10-3.82, p = .024). Furthermore, the presence of pedal MAC was significantly associated with an increased risk of mortality (p = .005), particularly among individuals with DFUs but without PAD (HR 4.26, 95% CI 1.90-9.52, p < .001), rather than in individuals presenting with both DFUs and PAD. CONCLUSION: The presence of pedal MAC is significantly associated with both amputation and mortality in individuals with DFUs. Moreover, pedal MAC could provide additional value to predict amputation other than PAD.

Related factors to illness perception of individuals with diabetic foot ulcers: A structural equation modelling test.

BACKGROUND: Diabetic foot is a common and severe complication of diabetes with limited movement, emotional distress, and poor quality of life. Illness perception was introduced to improve patients' psychological status and quality of life with diabetic foot ulcers. The aim of the study is to explore the related factors of illness perception, and to structure an illness perception model of patients with diabetic foot ulcers. METHODS: We recruited 208 patients with diabetic foot ulcers from six hospitals from April 2021 to February 2022. A multicentered cross-sectional study was conducted to collect the data. Questionnaires included illness perception, coping behavior, emotional status, and quality of life. We performed multiple linear regression analysis with illness perception as the dependent variable, and evaluated the goodness of fit of the resulting structural equations models based on covariance structural analysis. RESULTS: Illness perception was negatively related to coping behavior and quality of life, and it was positively correlated with yield-coping behavior, anxiety, and depression. The pain, diabetes duration, quality of life, yield-coping strategy, and sex were the factors that affected illness perception in patients with DFUs (P＜0.05). The resulting model was found to exhibit goodness of fit. CONCLUSION: Illness perception had an especially strong and direct impact on quality of life, depression, and anxiety. Therefore, it is significant to improve illness perception in patients with DFUs, and provide positive support based on cognitive behavioral therapy to improve illness perception, quality of life, and emotional status.

Prevalence and associated factors of hyperuricemia among Chinese patients with diabetes: a cross-sectional study.

Background: As a part of metabolic syndrome, hyperuricemia has a higher incidence in patients with diabetes than in the general population owing to various underlying factors. Objectives: The objective of the present study was to investigate the prevalence of hyperuricemia among patients with diabetes and identify associated factors. Design: A cross-sectional study. Methods: Herein, we included patients with diabetes managed at nine healthcare centers in Chenghua District, Chengdu, from February 2021 to November 2021. Clinical data, lifestyle habits, and laboratory data were collected to determine the prevalence and factors associated with hyperuricemia. Results: In total, we included 1577 patients with diabetes (males, 50.35%; females, 49.65%). The median serum uric acid level was 337.9 µmol/L, and the prevalence of hyperuricemia in patients with diabetes was 21.24%. The prevalence of hyperuricemia in male patients was significantly higher than in females (29.35% in males versus 13.03% in females, p < 0.001). Male patients with obesity (p = 0.006) or triglyceride (TG) ⩾ 1.7 mmol/L (p < 0.001) had a high risk of developing hyperuricemia, and hyperuricemia was negatively associated with estimated glomerular filtration rate (eGFR) ⩾ 60 mL/min/1.73 m2 (p < 0.001), glycosylated hemoglobin (HbA1c) ⩾ 7% (p < 0.001), fenofibrate (p = 0.010), and sodium-glucose cotransporter 2 (SGLT-2) inhibitors (p = 0.035). Considering females, overweight (p = 0.004), alanine transaminase (ALT) > 40 U/L (p < 0.001), and TG ⩾ 1.7 mmol/L (p = 0.015) showed a significant positive correlation with hyperuricemia, while eGFR ⩾ 60 mL/min/1.73 m2 (p < 0.001) was negatively associated with the risk of hyperuricemia. Conclusion: Hyperuricemia is highly prevalent in patients with diabetes, especially in males. In addition to traditionally associated factors, fenofibrate and SGLT-2 inhibitors were also associated with the risk of hyperuricemia. Registration: The study protocol was registered in the Chinese Clinical Trial Registry (http://www.chictr.org.cn/), and the registration number was ChiCTR 2100042742.

A Nationwide Cross-sectional Survey of Knowledge and Practices of Diabetes Drug Injection Techniques of Patients, Nurses, and Physicians: The China IT Improve Study.

OBJECTIVE: To investigate the knowledge and practices of diabetes drug injection techniques of diabetes patients, nurses, and physicians to support formulating national guidelines for standardized diabetes drug injection techniques. PATIENTS AND METHODS: In this nationwide multicenter cross-sectional survey conducted between November and December 2020, patients, nurses, and physicians were randomly chosen from 250 primary, 150 secondary, and 100 tertiary care hospitals using the stratified cluster sampling method. Their knowledge and/or practices of diabetes drug injection techniques were surveyed using the Diabetes Drug Injection Knowledge and Practice Questionnaire for Physicians, Nurses, and Patients. RESULTS: In total, 10,694, 2643, and 2816 eligible questionnaires were collected from patients, physicians, and nurses, respectively. Overall, 78.2% (7588/9709) type 2 diabetes patients failed to attain the target hemoglobin A1c. Hypoglycemic episodes and lipohypertrophy occurred in 19.8% and 34.7% of the patients, respectively. Needle reuse (odds ratio, 1.19; 95% CI, 1.07 to 1.33) and incorrect injection site rotation (odds ratio, 1.32; 95% CI, 1.16 to 1.51) were associated with failure to attain the target hemoglobin A1c. Overall, 48.9% physicians and 20.4% nurses had a poor knowledge domain score. Care setting and training, diabetes care experience, and regions were significant determinants of diabetes drug injection knowledge domain scores in both physicians and nurses. CONCLUSION: Poor glycemic control, occurrences of injection-associated complications in diabetes patients, and poor knowledge domain scores of a subset of physicians and nurses highlight the importance of regular assessment and education regarding diabetes drug injection techniques for physicians and nurses and development of national guidelines for diabetes drug injection. TRIAL REGISTRATION: Chictr.org.cn (ChiCTR2100045302).

Efficacy and safety of pentoxifylline for chronic venous leg ulcers: study protocol for a multicenter randomized controlled trial in China (ESPECT study).

BACKGROUND: Venous leg ulcers (VLUs) are the most severe manifestation of chronic venous disease, with long healing time and a high recurrence rate. It imposes a heavy burden on patients, their families, and the health care system. Chronic inflammation triggered by sustained venous hypertension is now recognized as the hallmark of chronic venous disease. The anti-inflammatory effect of pentoxifylline may offer a promising avenue to treat VLUs. However, current evidence of pentoxifylline for VLUs is relatively small and of low quality. The aim of this study is to evaluate the efficacy and safety of pentoxifylline for VLUs in the Chinese population. METHODS: This is a randomized, double-blinded, double-dummy, multi-center, placebo-controlled clinical trial. A total of 240 patients will be randomized to receive pentoxifylline (400 mg, twice daily) or placebo for 24 weeks. All participants will receive diosmin treatment and standard care of VLUs and other comorbidities. The primary outcome is the difference in the wound healing rate within 12 weeks between pentoxifylline and placebo. Secondary outcomes include (1) percent wound size changes at 12 weeks, (2) the levels of TNF-α and IL-6, (3) venous clinical severity score and chronic venous insufficiency quality of life score, and (4) ulcer recurrence within 24 weeks. DISCUSSION: This study would evaluate the efficacy and safety of pentoxifylline for VLUs in the Chinese population. If confirmed, it wound offer another effective and safe therapeutic option for treatment of VLUs. TRIAL REGISTRATION: The trial was registered at the Chinese Clinical Trial Registry (No. ChiCTR-2100053053). Registered on 10 November, 2021, https://www.chictr.org.cn/showproj.aspx?proj=137010.

The effects of daily dose and treatment duration of metformin on the prevalence of vitamin B12 deficiency and peripheral neuropathy in Chinese patients with type 2 diabetes mellitus: A multicenter cross-sectional study.

AIMS: To evaluate the prevalence of vitamin B12 deficiency in Chinese patients with type 2 diabetes mellitus receiving metformin treatment and to investigate the effects of metformin daily dose and treatment duration on the prevalence of vitamin B12 deficiency and peripheral neuropathy (PN). MATERIALS AND METHODS: In this multicenter cross-sectional study, 1027 Chinese patients who had been taking ≥1000 mg/day metformin for ≥1 year were enrolled using proportionate stratified random sampling based on daily dose and treatment duration. Primary measures included the prevalence of vitamin B12 deficiency (<148 pmol/L), borderline B12 deficiency (148 pmol/L-211 pmol/L), and PN. RESULTS: The prevalence of vitamin B12 deficiency, borderline deficiency, and PN were 2.15%, 13.66%, and 11.59%, respectively. Patients receiving ≥1500 mg/day metformin had significantly higher prevalence of borderline vitamin B12 deficiency (16.76% vs. 9.91%, p = .0015) and serum B12 ≤221 pmol/L (19.25% vs. 11.64%, p < .001) than patients receiving <1500 mg/day metformin. No difference was found in prevalence of borderline vitamin B12 deficiency (12.58% vs. 15.49%, p = .1902) and serum B12 ≤221 pmol/L (14.91% vs. 17.32%, p = .3055) between patients receiving metformin for ≥3 and <3 years. Patients with vitamin B12 deficiency had numerically higher PN prevalence (18.18% vs. 11.27%, p = .3192) than patients without it. Multiple logistic analyses revealed that HbA1c and metformin daily dose were associated with the prevalence of borderline B12 deficiency and B12 ≤221 pmol/L. CONCLUSIONS: High daily dosage (≥1500 mg/day) played an important role in metformin-associated vitamin B12 deficiency while not contributing to the risk of PN.

Clinical characteristics and risk factors of lower extremity amputation in the diabetic inpatients with foot ulcers.

Objectives: To analyze clinical characteristics of the diabetic inpatients with foot ulcers and explore the risk factors of lower extremity amputation (LEA) in West China Hospital of Sichuan University. Methods: A retrospective analysis was performed based on the clinical data of the patients with diabetic foot ulcer (DFU) hospitalized in West China Hospital of Sichuan University from January 1, 2012 to December 31, 2020. The DFU patients were divided into three groups: non-amputation, minor amputation, and major amputation groups. The ordinal logistic regression analysis was used to identify the risk factors for LEA. Results: 992 diabetic patients (622 males and 370 females) with DFU were hospitalized in the Diabetic Foot Care Center of Sichuan University. Among them, 72 (7.3%) (55 minor amputations and 17 major amputations) cases experienced amputation, and 21(2.1%) refused amputation. Excluding the patients who refused amputation, the mean age and duration of diabetes of and HbA1c the 971 patients with DFU, were 65.1 ± 12.3 years old, 11.1 ± 7.6 years, and 8.6 ± 2.3% respectively. The patients in the major amputation group were older and had longer course of diabetes for a longer period of time than those in the non-amputation and minor amputation groups. Compared with the non-amputation patients (55.1%), more patients with amputation (minor amputation (63.5%) and major amputation (88.2%)) suffered from peripheral arterial disease (P=0.019). The amputated patients had statistically lower hemoglobin, serum albumin and ankle brachial index (ABI), but higher white blood cell, platelet counts, fibrinogen and C-reactive protein levels. The patients with amputation had a higher incidence of osteomyelitis (P = 0.006), foot gangrene (P < 0.001), and a history of prior amputations (P < 0.001) than those without amputation. Furthermore, a history of prior amputation (odds ratio 10.194; 95% CI, 2.646-39.279; P=0.001), foot gangrene (odds ratio 6.466; 95% CI, 1.576-26.539; P=0.010) and ABI (odds ratio 0.791; 95% CI, 0.639-0.980; P = 0.032) were significantly associated with LEAs. Conclusions: The DFU inpatients with amputation were older with long duration of diabetes, poorly glycemic control, malnutrition, PAD, severe foot ulcers with infection. A history of prior amputation, foot gangrene and a low ABI level were the independent predictors of LEA. Multidisciplinary intervention for DFU is essential to avoid amputation of the diabetic patients with foot ulcer.

Prevalence of painful diabetic peripheral neuropathy in type 2 diabetes mellitus and diabetic peripheral neuropathy: A nationwide cross-sectional study in mainland China.

AIM: The study aimed to assess the prevalence and risk factors of painful diabetic peripheral neuropathy (PDPN) in patients with type 2 diabetes mellitus (T2DM) and diabetic peripheral neuropathy (DPN) in mainland China. METHODS: This nationwide cross-sectional study enrolled T2DM patients with DPN from 25 provinces in China between July 2017 and December 2017. The prevalence, characteristics, and risk factors of PDPN were analyzed. RESULTS: Among 25,710 patients with T2DM and DPN, 14,699 (57.2%) had PDPN. The median age was 63 years old. Age over 40 years old, education level, hypertension, myocardial infarction, duration of diabetes of over five years, diabetic retinopathy and nephropathy, moderate total cholesterol, moderate and higher low-density lipoprotein (LDL) increased uric acid (UA) and decreased estimated glomerular filtration rate (eGFR) were independently associated with PDPN (all P < 0.05). Compared with low levels of C-peptide, moderate levels were independently associated with a higher risk of PDPN, while high levels were associated with a lower risk (all P < 0.001). CONCLUSIONS: In mainland China, more than half of the patients with DPN have neuropathic pain. Patients with older age, lower education level, longer duration of diabetes, lower LDL, increased UA, decreased eGFR, and comorbidities had an increased risk of PDPN.

Development and Validation of a Questionnaire to Measure ICU Nurses' Knowledge, Attitudes, and Practices Related to Central Line Bloodstream Infection Practices.

BACKGROUND: Currently, there is no instrument available to assess intensive care unit (ICU) nurses' knowledge, attitudes, and practices (KAP) of central line-associated bloodstream infection (CLABSI) prevention practices. PURPOSE: To develop and validate a CLABSI questionnaire to measure ICU nurses' KAP (CLABSI-KAP-Q). METHODS: Data were collected from 255 nurses at 4 hospitals in Gansu Province, China. Questions on the CLABSI-KAP-Q were generated through a review of the literature, interviews with nurses, and multiple rounds of content validity evaluation by experts. The validity and reliability of the CLABSI-KAP-Q were assessed with exploratory factor analysis, confirmatory factor analysis, internal consistency, and correlation coefficients. RESULTS: The final version of the CLABSI-KAP-Q consisted of 32 items. The reliability was represented by a Cronbach α of 0.946, while the test-retest reliability was 0.945. The overall content validity was 0.95. CONCLUSIONS: The CLABSI-KAP-Q is shown to be valid and reliable and recommended for use in clinical practice.

[Clinical Characteristics and Prognosis of Diabetic Foot Ulcers Patients of Different Renal Function Statuses].

Objective: To explore the clinical characteristics and the prognosis of diabetic foot ulcers (DFU) inpatients of different renal function statuses. Methods: A retrospective analysis of 962 inpatients with DFU was conducted. The patients were divided into three groups according to their renal function statuses, and the clinical characteristics of the three groups were compared to identify differences. In addition, the patients were followed up in outpatient clinics or by telephone and their prognostic status and risk factors for death were analyzed. Results: Analysis of the clinical characteristics showed that, compared with diabetic patients with normal renal function or mild renal function impairment, diabetic patients with moderate and severe renal function impairment had a longer course of disease ( P<0.001). Patients with foot ulcers of Wagner grade 4 predominates the moderate and severe renal function impairment groups ( P<0.05). Patients in the moderate and severe renal function impairment groups had a relatively higher proportion of comorbidities, including hypertension, coronary heart disease, and peripheral arterial disease ( P<0.05). These patients had relatively lower levels of glycosylated hemoglobin and hemoglobin (all P<0.05) and relatively higher levels of neutrophil ratio and procalcitonin (all P<0.05). Of the two groups, patients in the moderate renal function impairment group were older ( P<0.001) and had lower ankle-brachial index ( P<0.001). The severe renal function impairment group had a higher proportion of patients with foot ulcers of Wagner grades 3 and 5 (all P<0.05). For the purpose of conducting prognostic analysis, 748 patients were followed up in outpatient clinics or by telephone for a median length of 41 months. Among them, 239 died. The all-cause mortality was 31.9%, and the mortality in the three groups was 25.8%, 46.2% ( P<0.001), and 59.4% ( P<0.001), respectively. The survival rate of patients in the moderate and severe renal function impairment groups was significantly lower than those in the normal renal function and mild renal function impairment groups ( P<0.001). Univariate Cox regression analysis showed that age, concomitant coronary heart disease and peripheral arterial disease, degree of renal function impairment, and foot ulcers of Wagner grade 4 and 5 were associated with all-cause deaths. Furthermore, multivariate Cox regression analysis showed that moderate and severe renal function impairment was an independent risk factor for all-cause deaths in DFU patients ( P<0.001). Conclusions: As renal function impairment worsens, patients with DFU present clinical characteristics of greater complexity, higher risks of cardiovascular events, and higher mortality. It is essential to prevent kidney damage and foot ulcers, to pay attention to the cardiovascular risks of DFU patients with moderate and severe renal function impairment, and to reduce mortality.

[Preliminary Application of Contrast-Enhanced Ultrasound in the Treatment of Diabetic Ulcers].

Objective: To investigate the role of contrast-enhanced ultrasound (CEUS) in the treatment of diabetic ulcers. Methods: The clinical data of 27 diabetic patients, who underwent CEUS examination of their ulcers in our hospital between April 2021 and July 2022 were collected. Among them, 26 patients suffered from diabetic foot ulcers, 5 of whom underwent amputation during hospitalization, and one patient suffered from hip ulcer. The 27 patients' mean age was (64.08±12.57) years. Fasting blood glucose levels of the patients were 3.36-34.61 mmol/L, with a mean of (10.62±8.77) mmol/L. Their glycosylated hemoglobin levels were 5.80%-10.70%, with an average of 7.96%±1.50%. Philips EPIQ7 ultrasound system with L9-3 linear probe of 3-9 MHz was used. First, the patients' ulcers were examined with conventional ultrasound to observe for abnormal echo. Then, 2.4 mL SonoVue (Bracco, Italy), a contrast agent, was injected intravenously through the elbow to look for effusion/pus, sinus tract, or dead space in the lesion area, and images were acquired. Results: Among the 27 patients, except for 5 with amputation stumps, 22 patients had wound areas ranging from 0.16 cm 2 to 215 cm 2, all being accompanied by sinus tract formation. Ten patients underwent ultrasound examination during their treatment. The positive rate of the results of conventional ultrasound was 50% (5/10) for identifying effusion/pus and pseudoaneurysm in the deep area of ulcers, while the positive rate of CEUS results was 100% (10/10). In addition to the lesions found by conventional ultrasound, CEUS also found large sinus tracts or dead spaces in the deep surface of ulcers in 5 additional patients. Of the 27 patients, 17 underwent ultrasound examination of the healing status of sinus tracts and dead spaces in the deep areas of ulcers before discharge. No sinus tracts in the deep areas of the ulcers were found by conventional ultrasound. However, relatively small dead spaces or sinus tracts in the deep areas of the ulcers were found in 10 patients by CEUS. Conventional ultrasound and CEUS found that 1 patient had a small amount of fluid in the amputation stump. In the remaining 6 patients, no deep sinus tracts in the ulcers were found by either conventional ultrasound or CUES, and the ulcers healed completely. Conclusion: By examining microvascular perfusion in diabetic wounds with CEUS, we can observe the extent of sinus tracts during treatment and whether the sinus tracts have healed or whether there are still dead spaces before patient discharge, which provides support for clinical decision-making concerning the treatment of diabetic ulcers.

The perceptions of living with diabetic foot ulcers: A systematic review and meta-synthesis of qualitative studies.

BACKGROUND: Diabetic foot ulcers are associated with decreased quality of life in patients with diabetes and impose a heavy burden on patients, their families, and the health care system. For health providers, a deeper understanding of the perceptions of patients is significant. They can provide better management and direction to patients with diabetic foot ulcers, thus improving their quality of life. OBJECTIVES: To synthesize the findings of qualitative studies to explore the perceptions of individuals living with diabetic foot ulcers. DESIGN: A systematic review and meta-synthesis of qualitative studies. METHODS: Published qualitative research articles were identified in PubMed, CINAHL, Embase, ISI Web of Science, Ovid, and Scopus from inception to January 2022, and bibliographical reports were reviewed. In addition, combing with the search for unpublished studies in the Google Scholar ProQuest Dissertations and Theses Database, we conducted a meta-synthesis. RESULTS: Fourteen articles were eligible for inclusion, and the total number of included individuals was 226, with ages ranging from 28 to 84 years. The perceptions of individuals with diabetic foot ulcers synthesized four overarching themes and their subthemes: perceptions of diabetic foot ulcers (Realization, Reasons), living with diabetic foot ulcers (Change in life, Physical burdens, Emotional burdens, Economic burdens), coping with diabetic foot ulcers (Hospital attendance, Attitude toward amputation, Treatment, Management), and expectations (Expectation of health-personnel, Future expectation). CONCLUSIONS: Individuals with diabetic foot ulcers suffer greatly in their physical, psychological, and social aspects. Comprehensive and individualized patient-centered care and appropriate families and social support for patients with diabetic foot ulcers should be provided.

Global mortality of diabetic foot ulcer: A systematic review and meta-analysis of observational studies.

AIM: To estimate the long-term mortality and risk factors in patients with diabetic foot ulcer (DFU). METHODS: We systematically searched Medline (PubMed), Embase, Scopus, Web of Science, Cochrane Library, China Science and Technology Journal Database (CQVIP), China National Knowledge Infrastructure, the Chinese Biomedical Literature Database (SinoMed) and Wanfang Data from 1 January 2011 to 31 July 2022. All observational studies that reported long-term mortality of patients with DFU were included. Random effect models were used to pool the reconstructed participant data from Kaplan-Meier curves. The primary outcome was the long-term survival of patients with DFU. An aggregate data meta-analysis was also performed. RESULTS: We identified 34 studies, with 124 376 participants representing 16 countries, among whom there were 51 386 deaths. Of these, 27 studies with 21 171 patients were included in the Kaplan-Meier-based meta-analysis. The estimated Kaplan-Meier-based survival rates were 86.9% (95% confidence interval [CI] 82.6%-91.5%) at 1 year, 66.9% (95% CI 59.3%-75.6%) at 3 years, 50.9% (95% CI 42.0%-61.7%) at 5 years and 23.1% (95% CI 15.2%-34.9%) at 10 years. The results of the aggregate data-based meta-analysis were similar. Cardiovascular disease and infection were the most common causes of death, accounting for 46.6% (95% CI 33.5%-59.7%) and 24.8% (95% CI 16.0%-33.5%), respectively. Patients with older age (per 1 year, hazard ratio [HR] 1.054, 95% CI 1.045-1.063), peripheral artery disease (HR 1.882, 95% CI 1.592-2.225), chronic kidney disease (HR 1.535, 95% CI 1.227-1.919), end-stage renal disease (HR 3.586, 95% CI 1.333-9.643), amputation (HR 2.415, 95% CI 1.323-4.408) and history of cardiovascular disease (HR 1.449, 95% CI 1.276-1.645) had higher mortality risk. CONCLUSIONS: This meta-analysis found that the overall mortality of DFU was high, with nearly 50% mortality within 5 years. Cardiovascular disease and infection were the two leading causes of death.

Refractory wounds induced by normal-renal calciphylaxis: An under-recognised calcific arteriolopathy.

BACKGROUND: Normal-renal calciphylaxis (NRC) is a devastating calcific vasculopathy characterised by refractory wounds. It is more likely to be misdiagnosed because of the absence of renal insufficiency. Failure to effectively control may lead to rapid deterioration and ultimately death. However, current knowledge of it is still inadequate. OBJECTIVES: To provide a relatively comprehensive review of NRC. METHODS: Nine electronic medical databases including PubMed, Web of Science, Embase, the Cochrane Library and so on were searched from inception to April 1, 2022. Articles in which calciphylaxis was diagnosed in patients with normal renal function were included. RESULTS: Totally 140 articles were retrieved with 187 patients (median age, 62 years [IQR, 49.63 ~ 75.70 years]; 83.42% female; 84.5% Caucasian). Vitamin K antagonism (43.32%) and diabetes (39.57%) accounted for most of the concomitant factors. Cutaneous presentations were the most common. Pathological confirmation was made in 97.86% of patients with an accuracy of 99.45%. Multidisciplinary therapeutic strategies were usually implemented while the final prognosis was not ideal, with a 6-month mortality rate of 21.10% and a 1-year mortality rate of 27.52%. CONCLUSION: NRC is an under-recognised disease caused by a variety of factors; meanwhile, multidisciplinary efforts are required to inform diagnostic and therapeutic decisions.

Association of vitamin D status with all-cause mortality and outcomes among Chinese individuals with diabetic foot ulcers.

AIMS/INTRODUCTION: The aim of this study was to examine the correlation between serum vitamin D concentrations and prognosis among Chinese individuals with diabetic foot ulcers (DFUs). MATERIALS AND METHODS: We retrospectively recruited 488 adults with DFUs in West China Hospital from 1 January 2012 to 31 December 2019. After telephone follow up, 275 patients were finally included. We compared serum vitamin D concentrations among DFUs patients with different prognostic status, and examined the association of vitamin D status with prognostic variables by Kaplan-Meier analysis. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for all-cause mortality. RESULTS: The median concentration of serum vitamin D of patients with DFUs was 37.78 nmol/L (interquartile range 27.91-50.66 nmol/L), with 31.6% having vitamin D deficiency (<30 nmol/L) and 42.2% having insufficient vitamin D (<50 nmol/L). During a median follow-up period of 52 months, 65 patients died, with an all-cause mortality of 23.64%. Vitamin D deficiency was independently linked to increased all-cause mortality after multivariable adjustments (hazard ratio 0.565, 95% confidence interval 0.338-0.946, P = 0.030). There were no significant differences between vitamin D concentrations and other outcomes of DFUs. Patients who suffered amputations had a tendency of lower vitamin D concentrations (34.00 [interquartile range 26.90-41.81] vs 40.21 [interquartile range 29.60-53.96] nmol/L, P = 0.053). CONCLUSIONS: Vitamin D deficiency was significantly associated with increased all-cause mortality in Chinese individuals with DFUs. Vitamin D supplementation might be a potential therapy for DFUs to prevent premature death and improve outcomes.

[Characteristics of Inflammatory Markers in Diabetic Foot Patients and Their Relationship With Prognosis of Diabetic Foot Ulcers]. / ç³–å°¿ç— è¶³æ‚£è€ ç‚Žç—‡æ ‡å¿—ç‰©ç‰¹å¾åŠå ¶ä¸Žè¶³æºƒç–¡é¢„åŽå ³ç³».

Objective: To explore the characteristics of baseline inflammatory markers in diabetic foot patients and their relationship with the prognosis of diabetic foot ulcers. Methods: The clinical data of diabetic foot patients (n=495) admitted to West China Hospital, Sichuan University since 2016 were retrospectively collected through the hospital electronic medical record system to analyze the characteristics of inflammatory markers and their relationship with the prognosis of diabetic foot ulcers. Results: White blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) levels were significantly higher in patients defined as grade 4 on the Wagner Scale than those in patients defined as grade 0-3 on the Wagner Scale. Neutrophil percentage (NE%) was higher in Wagner grade-4 patients than those in Wagner grade-0 and grade-1 patients and higher in Wagner grade-3 patients than those in Wagner grade-0 patients. NE%, CRP, PCT, and IL-6 levels were positively correlated with the severity of diabetic foot, with the respective odds ratio (OR) at 95% confidence interval (CI) being 1.038 (1.019-1.056), 1.019 (1.012-1.026), 8.225 (2.015-33.576), and 1.017 (1.008-1.025). Using Wagner grade-0 patients as the reference, patients with higher WBC were more likely to progress to Wagner grade 2, 3, and 4, with the respective OR (95% CI) values being 1.260 (1.096-1.447), 1.188 (1.041-1.356), and 1.301 (1.137-1.490); patients with higher ESR were more likely to progress to Wagner grade 3 and 4, with the respective OR (95% CI) values being 1.030 (1.006-1.054) and 1.045 (1.019-1.071). Baseline ESR (P=0.008), CRP (P=0.039), and IL-6 (P=0.033) levels were lower in patients who had received antibiotics prior to their admission than those in patients who had not received antibiotics before admission. The levels of WBC, NE%, ESR, PCT, and IL-6 were lower in the full recovery group than those in the group of patients who did not respond to treatment. The higher the levels of NE% and IL-6, the worse the prognosis of diabetic foot ulcers became, with the respective OR (95% CI) values being 1.030 (1.010-1.051) and 1.008 (1.002-1.013). Conclusion: The severity of diabetic foot ulcers increased with the rise in baseline levels of inflammatory markers. Elevated baseline NE% and IL-6 levels suggest a poor prognosis. Our findings suggest that early assessment of diabetic foot infection and standardized antibiotic therapy should be implemented to improve the prognosis.

Mesenchymal stem cell-derived exosomes: The dawn of diabetic wound healing.

Chronic wound healing has long been an unmet medical need in the field of wound repair, with diabetes being one of the major etiologies. Diabetic chronic wounds (DCWs), especially diabetic foot ulcers, are one of the most threatening chronic complications of diabetes. Although the treatment strategies, drugs, and dressings for DCWs have made great progress, they remain ineffective in some patients with refractory wounds. Stem cell-based therapies have achieved specific efficacy in various fields, with mesenchymal stem cells (MSCs) being the most widely used. Although MSCs have achieved good feedback in preclinical studies and clinical trials in the treatment of cutaneous wounds or other situations, the potential safety concerns associated with allogeneic/autologous stem cells and unknown long-term health effects need further attention and supervision. Recent studies have reported that stem cells mainly exert their trauma repair effects through paracrine secretion, and exosomes play an important role in intercellular communication as their main bioactive component. MSC-derived exosomes (MSC-Exos) inherit the powerful inflammation and immune modulation, angiogenesis, cell proliferation and migration promotion, oxidative stress alleviation, collagen remodeling imbalances regulation of their parental cells, and can avoid the potential risks of direct stem cell transplantation to a large extent, thus demonstrating promising performance as novel "cell-free" therapies in chronic wounds. This review aimed to elucidate the potential mechanism and update the progress of MSC-Exos in DCW healing, thereby providing new therapeutic directions for DCWs that are difficult to be cured using conventional therapy.

[Innovation Stimulates Development: How to Cope with the Constant Growth in Refractory Diabetic Foot Ulcers].

Diabetic foot ulcers, with an annual incidence as high as 8.1% in China, impose enormous social and economic burdens on diabetic patients, families and society. Substantial progress has been made in China in the work concerning diabetic foot ulcers in the past two decades, and the major amputation rate in patients with diabetic foot ulcers in China has decreased significantly, even though it is still far higher than the level of developed countries in Europe and North America. Therefore, if we are to further improve the diagnosis and treatment of diabetic foot ulcers in China, the only solution lies in reinforced efforts in innovation, including innovations in concepts, models, and technology, and the training of national and provincial-level leading experts in diabetic foot ulcer care. Only in this way, can we further reduce the disability and mortality caused by diabetic foot ulcers in China. We, herein, discussed the importance and necessity of establishing a comprehensive diabetic foot prevention and control system suited to the actual circumstances of China through strengthening innovative research. On that basis, we also reported existing problems and prospects for future development.