Con E de enfermera... Unidad de pie diabético / With E for nurse... Diabetic foot unit

En el 2015, el Hospital Fundación Jiménez Díaz (Madrid) creó la Unidad de Pie Diabético, un servicio en el que el cirujano vascular, el podólogo y las enfermeras van de la mano para prevenir las úlceras de los pies del paciente con diabetes y agilizar el diagnóstico temprano y el posible tratamiento. María Araujo Blesa, enfermera de esta unidad, nos explica cómo funciona y cómo trabajan para ayudar a los pacientes con diabetes, una enfermedad considerada como una pandemia creciente.(AU)

Contribution to the peripheral vasculopathy and endothelial cell dysfunction by CXCL4 in Systemic Sclerosis.

BACKGROUND: CXCL4, a chemokine with anti-angiogenic property, is involved in systemic sclerosis (SSc) related pulmonary arterial hypertension (PAH). OBJECTIVE: To investigated the contribution of CXCL4 to SSc development by focusing on the correlation of circulatory CXCL4 levels with their peripheral vasculopathy, and the effect of CXCL4 on endothelial cell dysfunction and the potential signaling. METHODS: We measured the plasma CXCL4 levels in 58 patients with SSc, 10 patients with the very early diagnosis of SSc (VEDOSS), and 80 healthy controls (HCs). Then, CXCL4 concentrations were correlated with clinical features, especially the peripheral vasculopathy. These observations were further validated in an additional cohort. Moreover, we studied the anti-angiogenic effects of CXCL4 and the underlying downstream signaling in human umbilical vein endothelial cells (HUVECs) in vitro. RESULTS: Circulating CXCL4 levels were 103.62 % higher in patients with SSc and 201.51 % higher in patients with VEDOSS than matched HCs, which were confirmed in two independent cohorts. CXCL4 levels were associated with digital ulcers (DU) and nailfold videocapillaroscopy (NVC) abnormalities in SSc. The proliferation, migration, and tube formation of HUVECs were inhibited by CXCL4 or SSc derived plasma, which reversed by CXCL4 neutralizing antibody, but failed by CXCR3 inhibitor. CXCL4 downregulated the transcription factor Friend leukaemia integration factor-1 (Fli-1) via c-Abl signaling. Furthermore, CXCL4 blocked the transforming growth factor (TGF) -ß or platelet-derived growth factor (PDGF) induced cell proliferation of HUVECs. CONCLUSIONS: CXCL4 may contribute to peripheral vasculopathy in SSc by downregulating Fli-1 via c-Abl signaling in endothelial cells and interfering angiogenesis.

Glucocorticoid-mediated induction of caveolin-1 disrupts cytoskeletal organization, inhibits cell migration and re-epithelialization of non-healing wounds.

Although impaired keratinocyte migration is a recognized hallmark of chronic wounds, the molecular mechanisms underpinning impaired cell movement are poorly understood. Here, we demonstrate that both diabetic foot ulcers (DFUs) and venous leg ulcers (VLUs) exhibit global deregulation of cytoskeletal organization in genomic comparison to normal skin and acute wounds. Interestingly, we found that DFUs and VLUs exhibited downregulation of ArhGAP35, which serves both as an inactivator of RhoA and as a glucocorticoid repressor. Since chronic wounds exhibit elevated levels of cortisol and caveolin-1 (Cav1), we posited that observed elevation of Cav1 expression may contribute to impaired actin-cytoskeletal signaling, manifesting in aberrant keratinocyte migration. We showed that Cav1 indeed antagonizes ArhGAP35, resulting in increased activation of RhoA and diminished activation of Cdc42, which can be rescued by Cav1 disruption. Furthermore, we demonstrate that both inducible keratinocyte specific Cav1 knockout mice, and MßCD treated diabetic mice, exhibit accelerated wound closure. Taken together, our findings provide a previously unreported mechanism by which Cav1-mediated cytoskeletal organization prevents wound closure in patients with chronic wounds.

A new application of the Rotterdam Diabetic Foot Study Test Battery: grading pedal sensory loss to predict the risk of foot ulceration.

AIMS: To assess the relationship between the degree of loss of foot sensation at baseline and incidence of foot ulceration (DFU). METHODS: Diabetic patients (n = 416) participating in the observational Rotterdam Diabetic Foot (RDF) Study were followed prospectively (median 955.5 days (IQR, 841.5-1121)). Subjects underwent sensory testing of the feet (39-item RDF Study Test Battery) at baseline and were assessed regarding incident DFU. Seven groups of incremental degree of sensory loss were distinguished, according to the RDF-39 sum score. Kaplan-Meier and regression analyses were used to determine the independent hazard of baseline variables for new DFU. RESULTS: 40 participants developed DFUs. The mean incident rate of new-onset ulceration from study start was 4.5 (95%CI: 3.3 to 6.1) per 100 person-years, which increased significantly from 0 to 67.70 in the seven groups (p < 0.0005). Predictors for DFUs were higher RDF-39 score (aHR: 1.173, p < 0.0005) and kidney function (aHR: 1.022, p = 0.016). Prior DFU suggests increased mortality risk. CONCLUSIONS: The degree of sensory loss at baseline was associated with progression to DFU during follow-up. Grading the loss of sensation using the RDF Study Test Battery may result in a more precise risk stratification compared to the use of the 10 g monofilament according to current guidelines.

Severe epidermolysis bullosa simplex phenotype caused by codominant mutations p.Ile377Thr in keratin 14 and p.Gly138Glu in keratin 5.

Epidermolysis bullosa simplex (EBS) is a rare skin disease usually inherited in an autosomal dominant pattern. EBS is resulting from mutations in keratin 5 (KRT5) and keratin 14 (KRT14) genes encoding the keratins 5 and 14 proteins expressed in the keratinocytes of the basal layer of the epidermis. To date, seven pathogenic mutations have been reported to be responsible for EBS in the Canadian population from the province of Quebec: p.Pro25Leu, p.Leu150Pro, p.Met327Thr and p.Arg559X in KRT5; p.Arg125Ser, p.Ile377Thr and p.Ile412Phe in KRT14. Here, we present a novel French-Canadian patient diagnosed with EBS confined to the soles but presenting a severe complication form including blisters, hyperkeratosis, skin erosions and toenail abnormalities. Mutation screening was performed by direct sequencing of the entire coding regions of KRT5 and KRT14 genes and revealed the previously reported missense heterozygous mutation c. 1130T > C in KRT14 (p.Ile377Thr). Furthermore, this patient is carrying a second mutation in KRT5, c.413G > A (p.Gly138Glu), which has been linked to an increased risk of basal cell carcinoma in the literature. We suspect an impact of the p.Gly138Glu variant on the EBS phenotype severity of the studied patient. The pathogenicity and consequences of both genetic variations were simulated by in silico tools.

In vitro biomechanical properties of sole tissues: Comparison between healthy and ulcerated bovine claws.

Sole ulcers are reportedly one of the most prevalent diseases associated with lameness in dairy cattle, significantly affecting animal welfare and farm profitability. The degree to which sole soft tissues, healthy or ulcerated, are able to maintain their structure and function when subjected to compressive forces remains unknown. Therefore, the aims of the present study were to assess sole tissue biomechanics in healthy and ulcerated claws and to describe correlated histology. Cylindrical samples were harvested from zones 4 and 6, as described by the international foot map, from hind lateral healthy (n = 12) and ulcerated bovine claws (n = 8; animals n = 12). Tissue biomechanics and morphology were evaluated via compressive tests and hematoxylin-eosin-phloxine-saffron staining, respectively. A 2-sample t-test was used to compare zones' mechanical properties between healthy and ulcerated tissues, and the Cochran-Mantel-Haenszel test was used to measure the effect of claw zone on histology. The fibril modulus (Ef) and permeability (k) respectively increased and decreased in ulcerated claws (Ef = 0.201 ± 0.104 MPa; k = 0.128 ± 0.069 mm2/MPa·s) compared with healthy claws (Ef = 0.105 ± 0.050 MPa; k = 0.452 ± 0.365 mm2/MPa·s) only for zone 6. Histology scores equal to or greater than 3 were associated with macroscopic presence of ulceration. A higher proportion of adipose tissue (30% or more) was associated with zone 6 compared with zone 4, but no difference was seen between healthy and ulcerated claws. Ulcerated claws had a higher prevalence of exostoses compared with healthy ones (33% vs. 8%). Sole soft tissues showed, as hypothesized, a viscoelastic behavior using unconfined compression testing, which, however, may not reflect in vivo loading conditions. Clinical and histological signs of sole ulceration were not associated with decreased strength of the supportive apparatus of the distal phalanx in zone 4 in this study.

Syphilis as osteomyelitis of the fifth metatarsal of the left foot: the great imitator hits once again.

INTRODUCTION: We report an unusual case of osteomyelitis of the left foot due to syphilitic bone involvement. CASE PRESENTATION: A 73-year-old man came to our attention with a four-month history of fever and a hypertrophic ulceration of the fifth metatarsal of the left foot. He had a history of syphilis treated years before. The CT scan showed an evident osteolytic area of the metatarsal phalangeal joint of the fifth left toe. The serological tests demonstrated a syphilitic reinfection. On suspicion of a bone localization of syphilis, an US-guided bone biopsy was performed. The histological examination with silver impregnation confirmed the diagnosis. The patient was treated with the traditional treatment of syphilis using penicillin, obtaining the complete resolution of the radiological and cutaneous alterations. CONCLUSIONS: The aim of this work is to sensitize clinicians to suspect syphilis in case of osteolytic lesions in patients with a history of this disease.

Use of disposable negative pressure wound therapy on split-thickness skin graft recipient sites for peripheral arterial disease foot wounds: A case report.

Split-thickness skin graft (STSG) helps to promote healing of wounds by providing a viable soft tissue cover. However, the success of which is influenced by how well it takes to the recipient site. Studies have demonstrated that negative pressure wound therapy (NPWT) is an excellent modality to promote graft survival. Technological advancements have made possible the invention of disposable, ultraportable, and mechanically operated versions for improved user experience. Alas, little has been discussed about their benefits on STSG. Therefore, the purpose of this case report is to highlight the effective use of disposable NPWT on freshly applied STSG. We report here a novel use of the disposable NPWT (SNAP therapy system) for STSG recipient sites in two patients with peripheral arterial disease (PAD) foot wounds. In both patients, there was 100% STSG uptake, and the lightweight disposable NPWT system makes for a more cost-effective and comfortable experience for patients. Disposable NPWT may be a feasible alternative to conventional NPWT to aid with STSG uptake for PAD foot wound recipient sites.

A new waterborne chitosan-based polyurethane hydrogel as a vehicle to transplant bone marrow mesenchymal cells improved wound healing of ulcers in a diabetic rat model.

Foot ulcers, a common complication of diabetes, can cause physical incapacity and are derived from several factors, including poor wound healing. New therapeutic strategies are needed to minimize this complication for the sake of patients' health. We therefore developed a new chitosan- polyurethane hydrogel membrane (HPUC) and the test results confirmed that HPUC present low cytotoxicity and improved wound healing when used with mononuclear bone marrow fraction cells in the diabetic rat model. The biodegradable hydrogels were produced in block copolymer networks with a combination of chitosan blocks and biodegradable polyurethane. The membranes were characterized by FTIR, 13C-NMR and thermogravimetry. Swelling and hydrolytic degradation were also evaluated. The non-solubility of the membranes in good solvents and the chemical characterization confirmed that the network structure was formed between the PU and the chitosan through urea/urethane bonds. The findings confirm that the HPUC have interesting properties that make them suitable for wound healing applications.

Outcome of Ray Resection as Definitive Treatment in Forefoot Infection or Ischemia: A Cohort Study.

Ray resection is frequently performed in cases of infection or ischemia, but the literature is scarce concerning its outcome as a definitive treatment. In this retrospective cohort study, we reviewed our cohort with transmetatarsal ray resection with a mean follow-up of 36.3 months. Reulcerations, transfer ulcers, and reamputations were determined. Risk factor analysis for revision surgery was conducted. Among 185 patients, 71 (38.4%) had revision surgery within a mean of 1.4 ± 2.6 years (range 2 days to 12.9 years), 22 (11.9%) had major amputations, 49 (26.5%) had minor amputations, 11 (5.9%) had same-ray reulceration, 40 (21.6%) had transfer ulceration, and 2 (1.1%) had both reulceration and transfer ulceration. Occurrence of a postoperative ulcer was statistically significantly associated with revision surgery (p < .01). In conclusion, metatarsal ray resection is a reasonable treatment option in cases of forefoot ischemia or infection to prevent major amputation but fails in 11.9%, and reulceration is associated with further revisions, making ulcer prevention paramount.

Successful Treatment of Chronic Lower Extremity Ulcers with Allogeneic Platelet-Rich Plasma and Artificial Dermis: A Case Report.

Hydroxyurea is an oral medication associated with painful, nonhealing ulcers, for which there is no effective treatment but permanent discontinuation of hydroxyurea. The authors present a case of leg ulcers that likely occurred as a result of hydroxyurea use in a patient with essential thrombocythemia. Topical treatment with allogeneic platelet-rich plasma and artificial dermis completely healed the leg ulcers without hydroxyurea cessation.

Predictors of lower extremity amputation in patients with diabetic foot ulcer: findings from MEDFUN, a multi-center observational study.

BACKGROUND: Lower extremity amputation (LEA) is a potential sequelae of diabetic foot ulceration (DFU) and is associated with huge morbidly and mortality. Low and middle income countries are currently at the greatest risk of diabetes-related complications and deaths. We sought to identify demographic, clinical and laboratory variables that significantly predict LEA in patients hospitalized for DFU. METHODS: The Multi-center Evaluation of Diabetic Foot Ulcer in Nigeria (MEDFUN) was an observational study conducted between March 2016 and April 2017 in six tertiary healthcare institutions. We prospectively followed 336 diabetic patients hospitalized for DFU and managed by a multidisciplinary team until discharge or death. Demographic and diabetes-related information and ulcer characteristics were documented. Patients were evaluated for neuropathy, peripheral arterial disease (PAD) and medical co-morbidities while relevant laboratory and imaging tests were performed. The study end-points were ulcer healing, LEA, duration of hospitalization and mortality. Here we present data on amputation. RESULTS: One hundred and nineteen subjects (35.4%) underwent LEA during the follow-up period. Univariate predictors of LEA were ulcer duration more than 1 month prior to hospitalization (P <  0.001), PAD (P <  0.001), Wagner grade ≥ 4 (P <  0.001), wound infection (P 0.041), Proteinuria (P 0.021), leucocytosis (P 0.001) and osteomyelitis (P <  0.001). On multivariate regression, only three variables emerged as significant independent predictors of LEA and these include: ulcer duration more than 1 month (O.R. 10.3, 95% C.I. 4.055-26.132), PAD (O.R. 2.8, 95% C.I. 1.520-5.110) and presence of osteomyelitis (O.R. 5.6, 95% C.I. 2.930-10.776). Age, gender, diabetes type and duration, neuropathy, glycemic control and anemia did not predict LEA in the studied population. CONCLUSION: We identified duration of ulcer greater than 1 month, PAD, Wagner grade 4 or higher, proteinuria, leucocytosis, wound infection and osteomyelitis as the significant predictors of LEA in patients hospitalized for DFU. Prompt attention to these risk factors may reduce amputation rate among these patients.

Standard complication screening information can be used for risk assessment for first time foot ulcer among patients with type 1 and type 2 diabetes.

AIM: Diabetic foot ulcer (DFU) is a major complication of both Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D); however research into risk factors for DFU does not separate between these two types. The purpose of the present investigation was to identify risk factors for development of first time DFU (FTDFU) over a period of 15 years in patients with T1D and T2D separately. METHODS: This retrospective cohort study included 25,220 feet from 5588 patients with T1D and 7113 patients with T2D treated in the period 2001-2015. Data on baseline characteristics and comorbidities were collected from electronic patient records. Influences of various risk factors for the development of FTDFU were assessed by hazard ratios (HR) from Cox proportional hazard regression models on time from enrolment to FTDFU diagnosis or end-of-follow-up. RESULTS: In T1D independent risk factors were male sex, age >60 years, high HbA1c, long diabetes duration, history of cardiovascular disease, macro-albuminuria, decreased visual acuity, advanced diabetic retinopathy, decreased/absent vibration sense, presence of patient reported symptoms of neuropathy, and absence of foot pulses. In T2D the independent risk factors were the same except age >60 years, a history of cardiovascular disease, and long diabetes duration. CONCLUSIONS: This study documents that much of the standard clinical information obtained as part of the routine follow-up are also independent risk factors for development of FTDFU. This may be used to create a basis for in which patient and when prevention should be started.