The international journal of lower extremity wounds最新文献

This review highlights key advances in diabetic neuropathy (DN) presented at the 2025 annual meetings of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). New studies confirmed the systemic impact of both diabetic peripheral neuropathy (DPN) and diabetic autonomic neuropathy (DAN). Cardiovascular autonomic neuropathy (CAN) was strongly linked with poor glycaemic control, impaired exercise tolerance, and increased risk of heart failure, particularly in patients with silent myocardial infarction. DSPN independently predicted stroke in type 1 diabetes. DN in general was associated with a higher risk of severe mental illness in type 2 diabetes. Therapeutically, dapagliflozin promoted corneal nerve regeneration through anti-inflammatory pathways. Novel biomarkers, such as plasma methylglyoxal, and advanced neuroimaging emerged as promising tools for risk stratification and personalised pain management. Machine learning applied to neuroimaging data identified neural connectivity patterns predictive of treatment response in painful DN. Basic science studies elucidated new mechanisms, including Schwann cell ferroptosis, and a gut-brain axis contributing to neuropathic pain and cognitive decline. Taken together, these findings promote our understanding of DN pathophysiology and therapy.

Diabetic foot infections (DFIs) caused by Pseudomonas aeruginosa are notoriously difficult to treat due to multidrug resistance, biofilm formation, and impaired tissue perfusion. This narrative review summarises emerging non-antibiotic and adjunctive therapies beyond conventional antimicrobial regimens. We highlight the potential of bacteriophage therapy, antimicrobial peptides, quorum sensing inhibitors, biofilm-disrupting enzymes, nanotechnology-based delivery systems, monoclonal antibodies, iron metabolism inhibitors, and photodynamic therapy. Each of these offers unique mechanisms to disrupt biofilms, neutralise virulence, or enhance immune clearance. In addition, we review advanced localized delivery platforms and diagnostic-guided personalized regimens optimizing intra-wound efficacy. Most of these novel interventions remain investigational, based on preclinical models, early-phase trials, or case reports. Nevertheless, they appear promising in managing chronic, refractory P. aeruginosa DFIs. Integration of these strategies into clinical practice will depend on robust clinical trials, regulatory clarity, and precision diagnostics. By moving beyond antibiotics, this evolving therapeutic landscape offers hope for improved outcomes in a population at high risk for limb loss and systemic complications.

BackgroundMultiple studies have shown metabolites may have potential effects on Charcot foot. However, the Mendelian randomization method has not yet explored the relationship between metabolites and Charcot foot.MethodsWe selected genetic variants from the publicly available Genome-wide Association Studies (GWAS) summary database to represent 1400 metabolites described in recent research. Mendelian randomization (MR) analysis was carried out to examine the relationships between these metabolites and Charcot foot. Significant single nucleotide polymorphism (SNP) data associated with exposure were screened out through association analysis. Valid instrumental variables (IVs) were then selected, excluding SNPs with F-statistic values below 10. The MR analyses primarily employed the inverse variance weighted (IVW) method. Bayesian weighted Mendelian randomization (BWMR), constrained maximum likelihood(cML), contamination mixture(Conmix), robust adjusted profile score(RAPS), and debiased inverse-variance weighted(deIVW) method were used to enhance the results. Colocalization analysis was performed to identify shared causal genetic variants associated with the resulting phenotypes. Sensitivity analyses, including assessments of Cochrane's Q test, egger intercept, and MR PRESSO test were conducted to confirm the robustness of the results.ResultsAfter preliminary MR exploration, the IVW results exhibited positive causal relationships between hexadecenedioate (C16:1-DC) levels (OR = 0.698, 95%CI: 0.586 to 0.831, P_FDR= 0.040), octadecadienedioate (C18:2-DC) levels (OR = 0.665, 95%CI: 0.552 to 0.800, P_FDR= 0.021), octadecanedioylcarnitine (C18-DC) levels (OR = 0.676, 95%CI: 0.553 to 0.827, P_FDR= 0.067) and Charcot foot. Colocalization analysis indicated that the above three metabolites share a common causal variant at the same genomic location with Charcot foot. Sixty-four metabolites with suggestive causal relationships with Charcot foot were also identified, among which 25 kinds of metabolites were positively correlated with Charcot foot, and 33 metabolites were negatively associated with Charcot foot. The BWMR, cML, Conmix, RAPS, and deIVW results supported our preliminary MR results. In several results, sensitivity analyses showed heterogeneity and horizontal pleiotropy, while the causal relationships obtained through FDR correction did not show any significant heterogeneity and horizontal pleiotropy. No reverse causal association was detected.ConclusionWe detected protective and risk metabolites in Charcot foot. Controlling metabolites may decrease Charcot foot risk and serve as a novel therapeutic biomarker for the therapy.

Applying infrared thermometry for temperature measurement is recommended for Charcot neuro-osteoarthropathy (CNO) diagnosis and monitoring of its course. Microwave radiometry (MWR) is used for the detection of temperature changes in human tissues. This study evaluates the agreement between these two methods in CNO assessment. Individuals with diabetes mellitus (DM) with and without active CNO were included. MWR measurements were performed by a microwave computer-based system that detects microwave radiation from the area under investigation and temperatures of the internal tissues. Sensors with diameters of 0.8 cm (MWR 0.8), 2 cm (MWR 2), and 5 cm (MWR 5) were used, with larger diameters enabling deeper tissue assessment. Nine individuals (mean age: 54.6 ± 15.7, 2 females) with active CNO and 5 people with DM without CNO were included in the study. The agreement between temperatures measured by infrared thermometry and by MWR 0.8 was high and the average temperature discrepancy between the two methods was 0.034 °C (P = .676). The average temperature discrepancy between infrared thermometry and MWR 2 was -0.323 °C (P < .001) and between infrared thermometry and MWR 5 was -0.315 °C (P = .002). Participants with active CNO were followed-up for a median period of 67 [39, 79] weeks. During follow up, the difference in skin temperature between the affected and the contralateral foot was lower than 2 °C in 7 (77.8%) participants. Three out of 5 individuals had re-activation of CNO in 21, 22 and 65 weeks after the removal of the offloading device, respectively. The decision to gradually start loading would be different only for one person if we had used MWR instead of infrared thermometry for the measurement of temperature difference between the affected and the contralateral foot. In conclusion, infrared thermometry showed high agreement with MWR 0.8 but not with MWR 2 or MWR 5.

BackgroundCharcot foot or Charcot neuropathic joint disease (CN) is a rare and complex foot disease with unknown pathogenesis, hindering early identification and intervention. The study aimed to clarify the causal association between all predominant risk factors and CN.MethodsTwo-sample Mendelian Randomization (MR), Multivariate MR, and Bidirectional MR analyses investigated the causal association between 36 modifiable risk factors and CN. The causal relationship between CN and Inflammatory cytokine and immune cells was also analyzed.ResultsGenetic factors associated with obesity and genetic susceptibility to various autoimmune diseases and non-cancerous thyroid diseases increased the risk of CN (P < .05), genetically associated high basal metabolic rate and high total cholesterol decreased the risk of CN (P < .05). In addition, we found a bi-directional causal relationship between CN and diabetes. In further immune cell analysis, we found 8 CN related immune cells, and in inflammatory cytokine analysis, we found 2 CN related inflammatory cytokines.ConclusionsThis comprehensive MR Study supports the causal role of Obesity-related factors, diabetes, autoimmune-related factors, and smoking in the development and progression of CN. This study identifies a potential cause of CN that has not been identified in previous studies and provides a new direction for further research.

IntroductionCharcot neuro-osteoarthropathy (CNO) occurs late in diabetes and may cause fracture, deformity, and higher mortality. Diabetic kidney disease (DKD) affects bone metabolism and contributes to mortality. However, there is no data on prevalence of CNO and its outcomes with coexisting DKD (or chronic kidney disease [CKD]).MethodsTo ascertain the prevalence of CKD (pick CKD or DKD) among patients with CNO and delineate the remission of active CNO and subsequent lower extremity amputation and all-cause mortality during prospective follow-up. Consecutive patients with diabetic CNO (active or inactive) were enrolled and subsequently divided into those with and without CKD (pick CKD or DKD) (Group A and Group B, respectively). A preestablished timeframe of 36 weeks was utilized to evaluate the remission proportion of active CNO.ResultsA total of 493 CNO patients were observed and 449 subjects (150 patients had active CNO) were further evaluated. The overall prevalence of diabetic nephropathy (DKD or CKD?) CNO was 43.7%. The proportion of patients achieving remission was significantly lower in Group A compared to Group B (OR 0.468, CI [0.239-0.934], P = .025), however, the median time for achieving remission was similar between the 2 groups (14 weeks vs 16 weeks, P = .885). Overall, all-cause mortality was notably higher Group A compared to Group B (OR 2.23, 95% CI [1.474-3.368]) over a median follow-up of 4 years. No significant differences were observed in rates of diabetic foot ulcers (58.2% vs 54.9%; P = .584) and amputations (17.4% vs 15.12%; P = .889) between Group A and Group B.ConclusionPatients of CNO with coexisting CKD have poor prognosis both in terms of likelihood of active CNO remission and higher mortality.

Euglycemic Diabetic ketoacidosis (E-DKA) is a life-threatening emergency characterized by ketonemia and metabolic acidosis in presence of relatively normal glycemic values. In recent years it has been associated with some predisposing conditions including sodium-glucose transporter 2 inhibitors (SGLT2-i) therapy, widely used in high-risk cardiovascular patients. We report the case of a 78-year-old diabetic woman treated with dapagliflozin, affected by critical limb threatening ischemia and septic osteoarthritis of interphalangeal joint of first right toe. At admission blood exams allowed diagnosis of E-DKA associated to acute kidney failure. The occurrence of the condition was probably due to foot infection acting on a trigger on a SGLT2-i predisposition. We treated the patient according to guidelines' indications achieving the resolution of the metabolic derangement. After the control of acute condition and return of metabolic parameters within the normal range, the patient underwent revascularization procedure and surgical debridement eventually obtaining complete healing of foot lesion.

Charcot neuro-osteoarthropathy (CNO) is a manifestation of peripheral neuropathy as a chronic complication of diabetes mellitus but, less frequently, can be associated to other conditions such as alcoholism or neurotoxic therapies. An increasingly emerging cause of CNO is the use of oncological drugs which can cause neuropathic damage. The use of these therapies dramatically increased in recent years. CNO leads to a progressive degeneration of the foot's joints and to bone destruction and resorption which ends in deformities. These alterations in the foot's anatomy determine a high risk of ulceration, infection, and osteomyelitis. The superimposition of osteomyelitis on CNO increases the risk of major amputation, already high in patients suffering either from only CNO or osteomyelitis alone. We report the case of a 61-year old nondiabetic woman affected by CNO as a consequence of antiblastic therapy for breast cancer and the subsequent overlap of osteomyelitis, confirmed by magnetic resonance imaging. This case underlines how it is necessary to consider CNO as a possible complication of antiblastic therapy in the view of the severe consequences of missing its diagnosis.