Search Results (92)

Diabetic foot ulcers are among the most severe complications of diabetes mellitus, disproportionately affecting populations in low- and middle-income countries. Digital health technologies have emerged as promising tools for prevention, diagnosis, and management; however, their effectiveness, usability, and applicability within public health systems remain insufficiently defined. This systematic review aimed to critically synthesize the clinical effectiveness, perceived usability, and methodological quality of digital interventions for the care of individuals with diabetes-related foot ulcers. A comprehensive search was performed in PubMed, Scopus, Web of Science, Embase, and Google Scholar for studies published between 2012 and 2024. Eighteen studies met the inclusion criteria, encompassing mobile health applications, wearable sensor devices, artificial intelligence-based tools, and telehealth platforms. Methodological quality was assessed using the Mixed Methods Appraisal Tool. Artificial intelligence-driven approaches demonstrated high diagnostic accuracy, with sensitivity and specificity above 90% for ulcer detection and classification. Mobile applications showed positive effects on self-efficacy, glycemic control, and adherence to preventive foot care, while usability scores were consistently high. Wearable sensor devices demonstrated potential for reducing ulcer recurrence, though supporting evidence remains limited. Across studies, recurrent methodological limitations included small sample sizes, absence of control groups, lack of economic evaluations, and barriers related to digital literacy and interoperability between systems. Most investigations were conducted in high-income countries, with limited consideration of public health contexts such as the Brazilian Unified Health System. In conclusion, digital health technologies show promise in improving the care of individuals with diabetes-related foot complications but face significant challenges regarding scalability, equity of access, and integration into public healthcare systems. Future research should prioritize context-adapted designs, robust clinical trials, and economic evaluations to inform health policies and support the rational adoption of these tools within universal health coverage frameworks. PROSPERO registration number: CRD420251023152. Full article

Autoantibodies targeting heterogeneous nuclear ribonucleoproteins (hnRNPs) have been seldom described in autoimmune diseases but remain poorly characterized in systemic sclerosis (SSc). This study aims to investigate the prevalence and clinical significance of anti-hnRNP autoantibodies in SSc. Serum samples from 25 well-characterized SSc patients were analyzed using protein immunoprecipitation (IP) to detect autoantibodies against hnRNP components A1, A2/B1, C1/C2, H, L, and U. Clinical data including organ involvement and autoantibody profiles were also collected over a 10-year follow-up period. Anti-hnRNP A2/B1 autoantibodies were identified in 40% of SSc patients and significantly associated with gastrointestinal involvement (80% vs. 27%; p = 0.015; OR 17, 95% CI 2.2–381). Additional components such as anti-hnRNP L antibodies exhibited variable protein-IP band patterns, with a trend toward an association between a “double” band pattern and cancer history (p = 0.066). Anti-hnRNP U antibodies were detected in a single patient presenting with severe digital ulcers. No patient tested positive for antibodies against other components, including A1, C1/C2, and H. In this preliminary hypothesis-generating study, anti-hnRNP autoantibodies were frequent in SSc patients with distinct prevalence and clinical associations depending on the target component. Anti-hnRNP A2/B1 correlate with gastrointestinal involvement but, contrary to previous reports, show no association with arthritis. Further exploration on anti-hnRNP L and the rarer anti-hnRNP U autoantibodies is warranted. Full article

This study presents the development of a quantitative evaluation method utilizing machine vision technology to characterize the extent of body surface damage in largemouth bass (Micropterus salmoides) infected with largemouth bass ranavirus (LMBV). High-resolution, multi-angle images (6000 × 4000 pixels) of the body surface from 239 infected specimens were acquired at a fixed distance of 40 cm using a SONY ILCE-7RM3 digital camera within a GODOX-LST60 softbox. Key parameters, including the number of segmented injury areas, the count of body surface lesions, and the total lesion area, were analyzed. These parameters were integrated through principal component analysis (PCA) to construct a comprehensive damage scoring model. The severity of viral-induced body surface damage was categorized into four grades: uninjured (0), minor injury (1), moderate injury (2), and severe injury (3). Histopathological examination revealed that early-stage infection (grade 1) predominantly exhibited localized hemorrhagic spots in the muscular region of the body side (B/E region) with limited lesion area. In contrast, moderate to severe infections (grades 2–3) were characterized by extensive ulceration, muscle necrosis, and visceral lesions, including hepatic fibrosis and splenic granulomatous formations. Quantitative real-time PCR (qRT-PCR) analysis demonstrated a progressive upregulation of pro-inflammatory cytokines (IL-6, IL-8, TNF-α, CXCL2) in immune organs, concomitant with increased expression of apoptosis-related genes (CASP8, CYC). This study successfully established a rapid and objective quantitative grading system for ranavirus infection, offering a novel technical approach for early diagnosis and precise prevention and control strategies against largemouth bass ranavirus. Full article

Systemic sclerosis (SSc) is a complex connective tissue disease that affects the skin and internal organs and is characterized by immune dysregulation, progressive fibrosis, and microvascular dysfunction. Chronic tissue ischemia, accompanied by impaired angiogenesis, leads to the gradual loss of small vessels, resulting in clinical complications, such as Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, and renal crisis. Emerging evidence highlights the crucial regulatory role of microRNAs (miRNAs) in vascular homeostasis through the modulation of key signaling pathways and endothelial cell activity. Dysregulated miRNAs influence fibroblast proliferation, inflammatory responses, and immune cell activity in SSc, contributing to disease progression. Current knowledge is still limited, highlighting the need for further research to elucidate the miRNAs network involved in the etiopathogenesis of SSc. The use of miRNA-based biomarkers is gaining tremendous attention for early diagnosis, risk stratification, classification, and the prediction of therapeutic responses. This review provides insights into angiogenesis-related miRNAs involved in SSc pathogenesis, discusses their relevance as biomarkers, and explores their promise as therapeutic targets. Advancing our knowledge of miRNAs-mediated regulatory networks may open new possibilities for personalized approaches to SSc management. Full article

Background: Detailed assessments, documentation, and evaluation of the wound characteristics in hard-to-heal wounds are essential for optimizing and individualizing wound care. However, the remaining challenge in clinical care includes the lack of high accuracy and precision tools for automated wound size (surface area and depth assessment) and a wound bed evaluation, i.e., a qualitative and quantification assessment of slough and necrosis. Objective/Methods: This study evaluates the accuracy and precision of the AI-powered technique, SeeWound© 2, compared to digital planimetry for a wound surface area and a wound bed characterization (slough and necrosis) in “in vitro” models and in patients, and a probe for depth, including diabetic foot ulcers, venous ulcers, pressure ulcers, and ischemic ulcers. Results: The data show that accuracy and precision (SeeWound© 2) for the wound surface area, the depth, and the wound bed characterization (slough and necrosis) were accuracy 96.28% and 90.00%, (CV 5.56%), respectively (wound size); 90.75% and 89.55%, (CV 3.07%), respectively (wound depth); 80.30% (slough) and 84.73% (necrosis) and 93.51% (slough) (CV 4.15%) and 82.35% (CV 8.34%) (necrosis). The precision for the digital planimetry was 88.61% (CV 7.00%) (slough) 85.74% (CV 7.54%) (necrosis). Conclusions: The overall accuracy and precision of the AI model in identifying wound size and depth were close to 90%, except for the accuracy and precision for slough and necrosis, where levels around 80% were achieved when compared to digital planimetry. The findings for the wound surface area and depth assessments, together with quantification of slough and necrosis, suggest that the SeeWound© 2 model can offer significant clinical benefits by improving documentation and supporting decision-making in wound management. Full article

Background: Digital ulcers (DUs) are among the most debilitating vascular complications in SSc and are commonly attributed to microvascular damage. However, recent evidence suggests a potential involvement of macrovascular abnormalities, including subclinical atherosclerosis and altered hemodynamic parameters. Objectives: This study aimed to investigate the association between a history of DUs and macrovascular involvement in SSc patients through carotid and vertebral Doppler ultrasonography, with a focus on hemodynamic indices such as Peak Systolic Velocity (PSV), End-Diastolic Velocity (EDV), Resistive Index (RI), and Intima–Media Thickness (IMT). Methods: A cross-sectional study was conducted on 107 SSc patients. Clinical, serological, cardiovascular, and metabolic data were collected, and carotid–vertebral ultrasound was performed. Patients were stratified based on DU history. Statistical analyses assessed associations between DU status and carotid–vertebral US findings. Results: Patients with DUs showed a significantly higher PSV in both right (86.9 ± 67.9 vs. 64.2 ± 20.5 cm/s, p = 0.010) and left ICA (78.9 ± 29.6 vs. 63.4 ± 18.2 cm/s, p = 0.002). Right ICA RI vas elevated in the DU group (p = 0.021). PSV in the external carotid arteries was also bilaterally increased in DU patients (p < 0.005). DU-positive patients had a higher prevalence of left carotid plaques (p = 0.012) and right-sided ICA RI > 0.75 (p = 0.01). Logistic regression identified DU history as an independent predictor of PSV at ICA (β = 31.89, p = 0.043) and carotid plaque presence at any side (OR 14.34, p = 0.012). Conclusions: A history of digital ulcers in SSc patients is associated with altered carotid hemodynamics and an increased subclinical atherosclerotic burden. These findings suggest that DUs may reflect not only microvascular damage, but also macrovascular dysfunction, supporting the need for integrated vascular assessment in SSc clinical practice. Full article

Pressure ulcers (PUs) are localized injuries caused by prolonged mechanical loading and ischemia, often leading to delayed healing and high recurrence rates. Although conventional treatments aim to support tissue repair, their efficacy remains limited, prompting interest in noninvasive therapies such as the pulsed electromagnetic field (PEMF). The PEMF has been reported to enhance cellular proliferation, re-epithelialization, and collagen remodeling, but its effects in pressure ulcer models, particularly concerning genetic background, remain unclear. This study investigated the therapeutic effects of the PEMF in a murine pressure ulcer model established by ischemia and reperfusion injury induced with externally attached magnets in two mouse strains, BALB/c and C57BL/6. The PEMF (10 Hz, 24 h per day) was used to treat PU-induced mice from day 4 to day 15 in BALB/c mice and to day 14 in C57BL/6 mice. Wound healing was assessed by gross morphological observation, histological analysis, and digital quantification of epidermal lesion length and collagen-positive area. In BALB/c mice, PEMF-treated wounds showed a modest trend toward improved re-epithelialization and collagen deposition, although the differences were not statistically significant. In contrast, C57BL/6 mice exhibited a significantly shorter length of epidermal lesion in the PEMF group on day 14, indicating enhanced epidermal regeneration. Collagen analysis showed comparable levels between treated and control groups in both strains, with no significant differences observed. To further assess the cellular response to PEMF, a scratch wound assay was conducted using HaCaT cells. Quantitative analysis demonstrated that PEMF treatment accelerated cell migration and wound closure in vitro. These findings suggest that PEMF enhances epidermal regeneration and keratinocyte mobility, with therapeutic responses potentially influenced by genetic background. This study supports the potential application of PEMF in pressure ulcer treatment and underscores the importance of strain selection in preclinical wound healing research. Full article

Systemic sclerosis (SSc) is a heterogeneous disease characterized by vascular alterations, immune dysregulation, and fibrosis. Solid evidence supports the hypothesis that endothelial dysfunction is the key player in SSc vascular injury and a critical factor concurring to the initiation of SSc pathogenesis. This narrative review reports on persistent endothelial dysfunction, resulting from oxidative stress, autoimmunity, and impaired vascular repair, in the course of SSc, and how it can trigger and sustain fibrotic remodeling of various organs. In this paper, we also analyze the impact on SSc of impaired angiogenesis and vasculogenesis, diminished endothelial progenitor cell function, and endothelial-to-mesenchymal transition, which can collectively disrupt vascular homeostasis and promote myofibroblast activation. These pathologic events underlie the hallmark clinical manifestations, i.e., Raynaud’s phenomenon, digital ulcers, pulmonary arterial hypertension, and scleroderma renal crisis. The review highlights how recognizing SSc as a paradigm of systemic endothelial dysfunction may reframe our understanding of its physiopathology, modify current therapeutic strategies, and unveil new therapeutic targets. Full article

Diabetic foot ulcers (DFUs) are a serious complication of diabetes, associated with high recurrence and amputation rates. Adherence to offloading devices is critical for wound healing but remains inadequately monitored in real-world settings. This study evaluates the SmartBoot edge-computing system—a wearable, real-time remote monitoring solution integrating an inertial measurement unit (Sensoria Core) and smartwatch—for its validity in quantifying cadence and step count as digital biomarkers of frailty, and for detecting adherence. Twelve healthy adults wore two types of removable offloading boots (Össur and Foot Defender) during walking tasks at varied speeds; system outputs were validated against a gold-standard wearable and compared with staff-recorded adherence logs. Additionally, user experience was assessed using the Technology Acceptance Model (TAM) in healthy participants (n = 12) and patients with DFU (n = 81). The SmartBoot demonstrated high accuracy in cadence and step count across conditions (bias < 5.5%), with an adherence detection accuracy of 96% (Össur) and 97% (Foot Defender). TAM results indicated strong user acceptance and perceived ease of use across both cohorts. These findings support the SmartBoot system’s potential as a valid, scalable solution for real-time remote monitoring of adherence and mobility in DFU management. Further clinical validation in ongoing studies involving DFU patients is underway. Full article

Background: The European League Against Rheumatism (EULAR), in collaboration with the European Scleroderma Trial and Research group (EUSTAR), published the first set of treatment recommendations for systemic sclerosis (SSc) in 2009, with subsequent updates in 2016 and 2023. Objectives: This study aimed to evaluate how rheumatologists’ clinical approaches to the treatment of SSc evolved following the 2016 update of the clinical management guidelines. Methods: Medication use for SSc was analyzed in a cohort of 378 patients. The patients were stratified based on enrollment before (233 patients) and after (145 patients) the guideline update, and medication usage was compared between the two groups. Results: Although all patients presented with Raynaud’s phenomenon (RP), only 35% received calcium channel blockers. Medications such as iloprost, phosphodiesterase type 5 (PDE-5) inhibitors, fluoxetine, and bosentan, recommended for the treatment of RP and digital ulcers, were not approved for SSc by the Republic Health Insurance Fund. Treatment for pulmonary arterial hypertension (PAH) was administered to only 16 patients (4.2%), including 2 who received bosentan, 10 who received PDE-5 inhibitors, and 4 who were treated with riociguat. The use of PDE-5 inhibitors increased following the 2016 update of the guidelines. Cyclophosphamide was consistently prescribed for interstitial lung disease (ILD), with an increased frequency observed after the guideline update. No significant differences were observed in the use of methotrexate for skin involvement, ACE inhibitors for scleroderma renal crisis, or antibiotics for gastrointestinal symptoms. Proton pump inhibitors (PPIs) were prescribed to 87.3% of patients with gastrointestinal involvement, with an increase in use of both PPIs and prokinetic agents following the guideline update. Conclusions: Rheumatologists’ adherence to the EULAR/EUSTAR guidelines varied considerably, with 25% to 100% of eligible patients receiving the recommended treatments. Concordance improved in the management of PAH, ILD, and gastrointestinal involvement after the 2016 guideline update. Full article

Background/Objectives: Systemic sclerosis (SSc) is a multisystemic chronic autoimmune disease, which leads to disability and possibly early retirement. The objective of our study was to explore the associations between employment status (ES) and demographic, clinical and functional features in a single-center EUSTAR cohort. Methods: Consecutive patients with SSc examined between November 2011 and June 2023, who were under the age of retirement in our country (62 years for women, 65 for men at the time), were included. All patients underwent a comprehensive clinical assessment and filled in a work assessment questionnaire as well as two validated health-related questionnaires: the Scleroderma Health Assessment Questionnaire (SHAQ) and the Duruoz Hand Index (DHI). Associations between ES and potential predictors (education level, disease characteristics, work conditions, SHAQ and DHI) were tested using logistic regression adjusted for age and gender. Results: Ninety-one patients (mean ± SD age 53.7 ± 11.8 years, twenty-two with diffuse skin involvement, fifty-six with a history of digital of digital ulcers (DUs)), were included. Only 22 patients were still employed, while 69 were retired, of which 38 retired because of SSc. Among the employed, nine performed manual labor, nine spent many hours standing and three had to work in a cold environment. When potential predictors were tested separately, adjusted for age and sex, patients with higher education (OR (95% CI) 11.36 (2.03–63.36), p = 0.006) and no history of digital ulcers had higher odds of being employed. The presence of joint contractures and weightlifting as a work demand were associated with unemployment. In a multivariable model, higher education (OR 5.91, 95% CI 0.97–36.09, p = 0.054 and younger age (OR 0.90, 95% CI 0.85–0.96, p = 0.001) were independently associated with continued employment. High school education did not show a significant effect (OR 0.089, 95% CI 0.015–0.530, p = 0.008). Patients with a history of digital ulcers had the lowest employment rates compared to those with no digital ulcer history. No significant associations were found between employment status and SHAQ or DHI scores. Conclusions: SSc is associated with significant work disability and early retirement. Higher education, the lack of Dus and younger age were highly associated with staying employed. Given the rarity of SSc, we consider that our good sample size (n = 91) reflects disease prevalence, but results should be tested in other studies and the single center should be considered when interpreting generalizability. Full article

Background: Several imaging studies have confirmed ocular involvement in systemic sclerosis (SSc). However, elastography has not yet been used for this purpose in the literature. Thus, this study aimed to evaluate ocular involvement in SSc using shear wave elastography (SWE). Methods: This study included 29 SSc patients and 30 age- and sex-matched healthy controls. All participants underwent independent ophthalmological evaluations by two ophthalmologists. Subsequently, SWE was used to evaluate the retina–choroid–sclera (RCS), optic disc (OD), optic nerve (ON), and retrobulbar adipose tissue (RBFT) of the right eye. The median shear wave elasticity (kPa) and velocity (m/s) values were automatically calculated using the ultrasound device’s integrated software. Results: The elasticity and velocity values of RBFT in SSc patients were significantly higher than those in the control group. However, no notable differences were observed in other analyzed areas. A strong association was found between digital ulcers and velocity values of the RCS, while no significant differences were noted for other parameters. Conclusions: This study revealed increased stiffness in the RBFT of SSc patients. To our knowledge, this is the first evidence suggesting that SSc can affect RBFT. Further studies are required to confirm this finding and investigate its link to the disease. Additionally, we found a strong association between digital ulcers and increased RCS stiffness. Using SWE for the first time, we have demonstrated that microcirculatory disruption in SSc extends beyond the skin and can affect multiple tissues simultaneously. Full article

A monocentric cross-sectional study was performed to investigate the role of serum calprotectin as a biomarker for disease severity and activity in systemic sclerosis (SSc). Serum calprotectin was measured in 74 consecutive SSc patients admitted to a tertiary hospital in Rome, and in 50 healthy controls (HCs) who were healthcare workers, using Aptiva’s particle-based multianalyte technology. In SSc patients, a statistically significant correlation was found between calprotectin and the modified Rodnan skin score (mRSS) (r = 0.402, p < 0.001), disease activity index (DAI) (r = 0.420, p < 0.001), disease severity scale (DSS) (r = 0.365, p < 0.01), forced vital capacity (FVC) (r = −0.459, p < 0.001), and diffusion lung capacity for carbon monoxide (DLco) (r = −0.445, p < 0.001). Calprotectin was higher in SSc patients with digital ulcers (DUs) than in SSc patients without DUs [2.98 mcg/mL (IQR 2.07;4.29) vs. 2.08 mcg/mL (IQR 1.71;2.45), p < 0.01] and in SSc patients with interstitial lung disease (ILD) compared to SSc patients without ILD [2.56 mcg/mL (IQR 1.94;3.03) vs. 1.96 mcg/mL (IQR 1.7;2.35), p < 0.01]. The multivariable stepwise logistic regression analysis showed calprotectin to be independently associated with DUs [OR 2.531 (CI 95%: 1.074;5.961), p < 0.05] and ILD [OR 3.687 (CI 95%: 1.336;10.170), p < 0.05] in SSc patients. Serum calprotectin is associated with DUs and ILD in SSc patients. Full article

Background/Objectives: Inflammatory bowel diseases (IBD), including mainly ulcerative colitis (UC) and Crohn’s disease (CD), have been associated with cognitive and psychological changes, though the mechanisms remain unclear. Methods: This prospective case-control study aimed to evaluate cognitive performance and biomarkers (homocysteine, serum amyloid A, brain-derived neurotrophic factor, and S100B protein) in IBD patients. Results: A total of 90 individuals (34 UC, 21 CD, and 35 controls) were assessed using the Montreal Cognitive Assessment (MoCA), the Memory Impairment Index (MIS), and biomarker analysis. MoCA and MIS testing showed significant differences between UC, CD, and the controls, with lower scores observed in IBD groups (p = 0.003, p = 0.015). Regarding trail-making tests, digit symbol substitution tests, and forward and backward digit spans, no significant changes were observed. No functional deficits were observed in daily activities. Biomarker analysis revealed lower brain-derived neurotrophic factor and higher serum amyloid A levels in IBD patients, correlated to MOCA and MIS scores. There were no significant differences in psychological distress between IBD patients and the controls. Subtle cognitive declines were noted across all groups during the 1-year follow-up, without any statistical significance when groups were compared. Conclusions: In conclusion, IBD patients reported lower cognitive scores compared to the controls, while no differences in depression and anxiety scores were observed. Higher BDNF levels correlated with better cognitive functioning, while higher serum amyloid A correlated with lower cognitive functioning. Full article

Background: The UK has a high incidence of lameness in cattle, which is costly in terms of economics and welfare. Most causes of bovine lameness originate in the foot but there are several different conditions causing lameness. Quantifying the relative prevalence of different lameness causing lesions allows for the focus of preventative measures and research on the most common conditions. Methods: This study analysed trimming records from 23 professional foot trimmers working in the Southwest of England. A total of 97,944 recorded lesions over a 5-year period were analysed for lesion identity, lesion severity, repeat presentation, foot affected, claw affected and whether they were from dairy or beef cattle. Results: The most frequently recorded lesions were digital dermatitis (32%), white line disease (21%), sole ulcer (19%) and sole haemorrhage (13%). White line disease had the highest percentage of lesions requiring veterinary attention and most frequently re-presented. Most lesions were in hind feet and there was a small but significantly greater number recorded in right feet. Beef cattle had a higher percentage of digital dermatitis and lower percentage of sole ulcer compared with dairy cattle. Conclusions: Digital dermatitis was the most common foot lesion of all cattle types. Most feet with lesions only appeared in the data set once, suggesting broadly that foot trimming was largely effective at resolving new foot lesions. More white line lesions were re-presented, along with having more severe grades compared with other lesions. Therapeutic trimming of chronic lesions appeared to be less successful, with re-presentations, on average, every 93 days, compromising welfare for extended periods, and requiring consideration of different veterinary treatment options. Full article