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.

Neutrophil Extracellular Traps Are Markers of Wound Healing Impairment in Patients with Diabetic Foot Ulcers Treated in a Multidisciplinary Setting.

Objective: Neutrophil extracellular traps (NETs) are associated with impaired wound healing in diabetes. This study evaluates the association between NET-specific markers and wound healing among diabetic foot ulcer (DFU) patients treated in a multidisciplinary setting. Approach: Clinical data of diabetic patients with active foot ulcers who presented to our team between January 1, 2016 and June 30, 2017 were recorded. The diabetic ulcer severity score (DUSS) and wound, ischemia, and foot infection (WIfI) score were calculated. NET-specific markers in plasma and wound tissues were tested. The capacity for plasma and platelets to prime neutrophils to release NETs was assessed. The prognostic value of NET-specific markers for wound healing was evaluated. Results: NET-specific markers were significantly higher in DFU patients than in diabetic patients without DFU or healthy controls and were found to correlate positively with DUSS or WIfI score. Elastase levels in ulcer tissue significantly increased in wounds with infections and delayed healing. Higher levels of NET release were observed after the stimulation of plasma or platelets from ulcer-related vessels than from nonulcer-related vessels of the DFU patients. Citrullinated histone 3 (citH3) was identified as a risk factor for wound healing impairment and amputation. The patients with the highest quartile of citH3 levels presented significantly lower healing rates and higher amputation rates than those with the lower three quartiles. Innovation: This study extended current knowledge of NETs on wound healing in DFU patients. Conclusion: NET-specific markers negatively correlated with wound healing in DFU patients, and citH3 is a potential marker.

Platelet to lymphocyte ratio correlates with diabetic foot risk and foot ulcer in patients with type 2 diabetes.

Diabetic foot ulcer is a major complication in patients with diabetes. Platelet-lymphocyte ratio (PLR) has been reported to have a predictive effect to some diabetic complications in recent years. However, it has not been fully elucidated about the relationship between diabetic foot risk or diabetic foot ulcer and PLR in patients with type 2 diabetes. Therefore, we aimed to evaluate this relationship. In this cross-sectional study, we evaluated the relationships between patient's diabetic foot risk with the criteria of the International Working Group on the Diabetic Foot (IWGDF) and prevalent foot ulcer, and PLR in 453 consecutive patients with type 2 diabetes. Propensity score analysis was used to adjust the difference of covariates; age, sex, duration of diabetes, body mass index (BMI), HbA1c, current smoking, hypertension, dyslipidemia, neuropathy, PAD, foot deformity and history of foot ulcers. PLR was higher in patients with high risk diabetic foot or foot ulcer (117 ± 40 vs. 107 ± 31, p = 0.003 and 148 ± 65 vs. 113 ± 56, p < 0.001). A receiver-operating characteristic curve demonstrated that PLR of 130.6 constitutes the cut-off value for prevalent foot ulcer with sensitivity 0.85 and specificity 0.70. Multivariate logistic regression analysis revealed that PLR was positively correlated with prevalent foot ulcer (odds ratio, 1.02; 95% confidence interval 1.01-1.04, p = 0.003) after adjusted for several variables with propensity score analysis. Our results demonstrated that PLR can be a marker for high risk diabetic foot and diabetic foot ulcer in patients with type 2 diabetes.

Retrospective Cohort Analysis of Pedal Procedures in the Thrombocytopenic Patient.

Thrombocytopenia is an important medical condition to understand prior to performing procedures in the foot and ankle. We have set forth to highlight factors a physician should take into consideration before performing procedures in the thrombocytopenic patient. A retrospective cohort analysis at a large academic institution was undertaken utilizing a cohort discovery tool to discover incidence and management strategies for patients with foot-related conditions that require in-office procedures. We demonstrate that a full history and physical are important to guide treatment along with complete blood count testing prior to intervention. We included all patients at the institution that underwent a foot and ankle procedure in-office with podiatric surgery over 10 years where thrombocytopenia was demonstrable via complete blood count within 3 months of the procedure. Patients' charts were reviewed for 1 year following podiatric intervention and outcomes were recorded. The cohort reveals that patients with thrombocytopenia have many advanced comorbidities but performing procedures in this cohort is safe. Complications from procedures included erythrocyte transfusion, ulcer recurrence, need for formal surgical intervention, infection, falls, and death. We then provide a brief discussion about the etiology and management options available for thrombocytopenia.

Is there any difference in tetanus IgG levels of diabetic patientswith respect to the presence of foot ulcers?

BACKGROUND/AIM: The aim of this study was to reveal the tetanus immunization status of diabetic patients and to determine whether diabetic patients with foot ulcers have different TIG levels. MATERIALS AND METHODS: A cross-sectional study was designed that included diabetic patients with foot ulcers (n = 30) and diabetic patients without ulcers (n = 30). The groups were compared for serum TIG levels along with total serum protein, albumin, C-reactive protein (CRP), and total immunoglobulin G (Ig G). RESULTS: For diabetic patients without foot ulcers, 17 of 30 (56.6%) patients were found to have nonprotective TIG levels whereas for diabetic patients with foot ulcers, 28 of 30 (93.3%) patients were found to have nonprotective TIG levels. The mean value of TIG for diabetic patients without foot ulcers was 0.345 ± 0.281 IU/mL and for diabetic patients with foot ulcers the mean TIG value was 0.055 ± 0.033 IU/mL. Statistically significant differences were observed in TIG (P = 0.008), total protein (P < 0.001), albumin (P < 0.001), and CRP levels (P < 0.001) between the two groups. CONCLUSION: The majority of the diabetic patients had low TIG levels and they were significantly lower in diabetic patients with ulcers. A booster dose of tetanus vaccine should be considered for diabetic patients with and without diabetic foot ulcers.

The role of procalcitonin as a marker of diabetic foot ulcer infection.

Foot ulcers are frequent in diabetic patients and are responsible for 85% of amputations, especially in the presence of infection. The diagnosis of diabetic foot ulcer infection is essentially based on clinical evaluation, but laboratory parameters such as erythrocyte sedimentation rate (ESR), white blood count (WBC), C-reactive protein (CRP) and, more recently, procalcitonin (PCT) could aid the diagnosis, especially when clinical signs are misleading. Fifteen diabetic patients with infected foot ulcers were admitted to our department and were compared with an additional group of patients with non-infected diabetic foot ulcers (NIDFUs). Blood samples were collected from all patients in order to evaluate laboratory markers. In the current study, the diagnostic accuracy of PCT serum levels was evaluated in comparison with other inflammatory markers such as CRP, ESR and WBC as an indicator to make the distinction between infected diabetic foot ulcers (IDFUs) and NIDFUs. CRP, WBC, ESR and especially PCT measurements represent effective biomarkers in the diagnosis of foot infections in diabetic patients particularly when clinical signs are misleading.

Acute and chronic effects of therapeutic apheresis.

In most patients only a few sessions of apheresis treatment are necessary to see the benefit. This is the case of immunological diseases when the production of a pathologic component is limited in time or in microcirculation disturbances when changes of vascular function may occur. In the first instance the acute effect is likely due to the removal of the corresponding antibody, while in the second case the improvement of the endothelium-dependent vasodilation and the reduction of blood viscosity play a major role. In long-term treatment, as in the case of patients affected by familial hypercholesterolemia, the chronic effects of apheresis may lead to the repair of morphological alterations in the vascular wall. We report the recovery from ulcers in two hemodialysis patients suffering from peripheral arterial disease as the result of twenty-two sessions of rheopheresis. The reasons that justify these chronic actions may involve pleiotropic effects that are different according to the apheresis technique used.

Can procalcitonin predict bone infection in people with diabetes with infected foot ulcers? A pilot study.

AIMS: The diagnosis of osteomyelitis is a key step of diabetic foot management. Previous studies showed that procalcitonin (PCT), a novel infection marker, is superior to conventional infection markers in the diagnosis of diabetic foot infection. This study aimed to investigate the serum levels of PCT and other conventional infection markers in diabetic persons with and without osteomyelitis. METHODS: Twenty-four patients (18 male, mean age: 61.9±10.8 years) with infected foot ulcers were prospectively enrolled. Clinical characteristics of the wounds were noted. Blood samples were obtained for biochemical analysis. Magnetic resonance imaging of the foot was performed in all patients to diagnose osteomyelitis. RESULTS: Osteomyelitis was found in 13 of 24 (54%) patients. PCT levels were 66.7±43.5 pg/ml in patients with osteomyelitis and 58.6±35.5 pg/ml in patients without osteomyelitis. The difference did not reach statistical significance (p=0.627). Erythrocyte sedimentation rate, but not C-reactive protein and white blood cell count, was found significantly higher in patients with osteomyelitis. CONCLUSION: In this group of patients, PCT failed to discriminate patients with bone infection. Erythrocyte sedimentation rate can be used as a marker of osteomyelitis in diabetic persons.

Transcutaneous oxygen tension: a useful predictor of ulcer healing in critical limb ischaemia.

OBJECTIVE: To investigate the threshold of transcutaneous oxygen tension (TcPO(2)) values in predicting ulcer healing in patients with critical limb ischaemia in a prospective study. METHOD: 50 patients suffering from critical limb ischaemia with chronic ischemic ulcers or gangrenous toes were enrolled in this study between January and December 2008. Their demographic data and ankle brachial pressure index (ABPI) were collected. Baseline ulcers were measured with a wound measurement system (Visitrak, Smith & Nephew). TcPO(2) was measured at rest in the supine position and with 30 degrees leg elevation. The patients with infective and ischemic ulcers underwent debridement and gangrenous toes were amputated. Ulcer outcome was classified as either: (1) A healing ulcer, showing good epithelialisation or granulation at both base and edges, or a decrease in ulcer area during the study; or (2) A non-healing ulcer, showing poor granulation tissue formation or a pale base and necrotic edges, or deterioration in an ischaemic ulcer. RESULTS: The mean age of the patients was 67.6 + or - 10.8 years. The most common risk factor was hypertension (90%). Mean ABPI was 0.75 + or - 0.39. 13 patients (26%) had a TcPO(2) of less than 20 mmHg, of which none showed any improvement in ulcer healing (p<0.001). 15 patients (30%) had a TcPO(2) of more than 40 mmHg, of which all progressed to complete ulcer healing (p<0.001). In the borderline group (20-40 mmHg, 22 patients, 44%), 10 patients (45%) had a TcPO2 drop of <10 mmHg with 30 degrees leg elevation, of which 8 achieved complete ulcer healing (p<0.001). 12 patients (55%) had a TcPO(2) drop of >10 mmHg with 30 degrees leg elevation, of which 11 showed no ulcer healing (p<0.001). CONCLUSION: TcPO(2) measurement is an accurate, non-invasive, and good predictor of ischemic ulcer healing, for cut-off TcPO(2) values of less than 20 mmHg and more than 40 mmHg. In addition, the leg elevation method for TcPO(2) might provide an important adjunct in the assessment of patients with borderline values.

History of foot ulcer increases mortality among individuals with diabetes: ten-year follow-up of the Nord-Trøndelag Health Study, Norway.

OBJECTIVE: To compare mortality rates for individuals with diabetes with and without a history of foot ulcer (HFU) and with that for the nondiabetic population. RESEARCH DESIGN AND METHODS: This population-based study included 155 diabetic individuals with an HFU, 1,339 diabetic individuals without an HFU, and 63,632 nondiabetic individuals who were all followed for 10 years with mortality as the end point. RESULTS: During the follow-up period, a total of 49.0% of diabetic individuals with an HFU died, compared with 35.2% of diabetic individuals without an HFU and 10.5% of those without diabetes. In Cox regression analyses adjusted for age, sex, education, current smoking, and waist circumference, having an HFU was associated with more than a twofold (2.29 [95% CI 1.82-2.88]) hazard risk for mortality compared with that of the nondiabetic group. In corresponding analyses comparing diabetic individuals with and without an HFU, an HFU was associated with 47% increased mortality (1.47 [1.14-1.89]). Significant covariates were older age, male sex, and current smoking. After inclusion of A1C, insulin use, microalbuminuria, cardiovascular disease, and depression scores in the model, each was significantly related to life expectancy. CONCLUSIONS: AN HFU increased mortality risk among community-dwelling adults and elderly individuals with diabetes. The excess risk persisted after adjustment for comorbidity and depression scores, indicating that close clinical monitoring might be warranted among individuals with an HFU, who may be particularly vulnerable to adverse outcomes.

Evaluation of diabetic foot ulcer healing with hyperspectral imaging of oxyhemoglobin and deoxyhemoglobin.

OBJECTIVE: Foot ulceration remains a major health problem for diabetic patients and has a major impact on the cost of diabetes treatment. We tested a hyperspectral imaging technology that quantifies cutaneous tissue hemoglobin oxygenation and generated anatomically relevant tissue oxygenation maps to assess the healing potential of diabetic foot ulcers (DFUs). RESEARCH DESIGN AND METHODS: A prospective single-arm blinded study was completed in which 66 patients with type 1 and type 2 diabetes were enrolled and followed over a 24-week period. Clinical, medical, and diabetes histories were collected. Transcutaneous oxygen tension was measured at the ankles. Superficial tissue oxyhemoglobin (oxy) and deoxyhemoglobin (deoxy) were measured with hyperspectral imaging from intact tissue bordering the ulcer. A healing index derived from oxy and deoxy values was used to assess the potential for healing. RESULTS: Fifty-four patients with 73 ulcers completed the study; at 24 weeks, 54 ulcers healed while 19 ulcers did not heal. When using the healing index to predict healing, the sensitivity was 80% (43 of 54), the specificity was 74% (14 of 19), and the positive predictive value was 90% (43 of 48). The sensitivity, specificity, and positive predictive values increased to 86, 88, and 96%, respectively, when removing three false-positive osteomyelitis cases and four false-negative cases due to measurements on a callus. The results indicate that cutaneous tissue oxygenation correlates with wound healing in diabetic patients. CONCLUSIONS: Hyperspectral imaging of tissue oxy and deoxy may predict the healing of DFUs with high sensitivity and specificity based on information obtained from a single visit.

Immune mediators in patients with acute diabetic foot syndrome.

OBJECTIVE Subclinical inflammation is an important risk factor for type 2 diabetes and diabetes complications. However, data on the association between inflammation and acute diabetic foot syndrome are scarce. The aim of this study was to compare systemic immune mediators in diabetic patients with and without an ulcer and to identify modulating factors. RESEARCH DESIGN AND METHODS Circulating levels of acute-phase proteins, cytokines, and chemokines were measured in diabetic patients with an ulcer (n = 170) and without an ulcer (n = 140). Of the patients, 88% had type 2 diabetes. RESULTS Patients with an acute foot ulcer had higher levels of C-reactive protein (CRP), fibrinogen, interleukin (IL)-6, macrophage migration inhibitory factor, macrophage inflammatory protein-1alpha, and interferon-gamma-inducible protein-10 as well as lower levels of RANTES (regulated on activation normal T-cell expressed and secreted) (all P < 0.01). No differences were found for IL-8, IL-18, and monocyte chemoattractant protein-1. Most of these associations persisted after adjustment for demographic and anthropometric data, metabolic confounders, and diabetes complications. In multivariate models, size of ulcer according to the University of Texas classification but not the grade of infection was independently associated with three markers of subclinical inflammation (CRP, IL-6, and fibrinogen). CONCLUSIONS We demonstrate in our cross-sectional study that acute foot ulcers and their severity are associated with a marked upregulation of acute-phase proteins, cytokines, and chemokines independently of the concomitant infection. Further studies should investigate whether an activation of the immune system precedes the development of foot ulcer and whether anti-inflammatory therapies might be effective.

An unusual case of toe ulceration.

We describe an unusual presentation of toe ulceration in a 39-year-old otherwise healthy man. The left fifth toe was painful for several months with ulceration at the tip. The other toes appeared cyanotic and discolored. Foot pulses were normal. Laboratory testing revealed the platelet count at 1208 thousand/microliter, with hemoglobin 19.2g/dl and hematocrit 57%. The erythropoietin level was found to be markedly decreased at 1 mU/ml. The patient was given the diagnosis of polycythemia vera with iron deficiency. Phlebotomy was performed and aspirin and cytoreductive therapy with hydroxyurea was prescribed with resolution of the toe ulceration.

Increased activity of factor VIII coagulant associated with venous ulcer in a patient with Klinefelter's syndrome.

Klinefelter's syndrome is the most frequent major abnormality of sexual differentiation in men with two or more X chromosomes. Recurrent venous ulcers as a result of a post-thrombotic syndrome are a well known symptom in patients with Klinefelter's syndrome. Until now the underlying pathomechanisms are not completely understood. Platelet hyperaggregability, factor V Leiden mutation and abnormalities in fibrinolysis were implicated as possible contributing factors. Here we describe the detection of an increased activity of factor VIII coagulant (factor VIII:C). This is the first case report on increased factor VIII:C activity associated with venous ulcers in a patient with Klinefelter's syndrome. Elevated factor VIII plasma levels are gradually accepted to be associated with an increased risk for venous thromboembolism. Therefore, we discuss that the examination of factor VIII:C may help in clarifying individual thromboembolic risks, especially in patients with Klinefelter's syndrome.

Extracorporeal fibrinogen adsorption--efficacy, selectivity and safety in healthy subjects and patients with foot ulcers.

The elimination of fibrinogen from plasma improves plasma viscosity and whole blood viscosity. For extracorporeal adsorption of fibrinogen the pentapeptide gly-pro-arg-pro-lys was coupled to sepharose CL-4B. Columns containing 100 ml of coupled sepharose CL-4B were used to eliminate fibrinogen from the plasma of 8 healthy male subjects (mean age 27.4 +/- 4.3 years, height 180.9 +/- 8.3 cm, weight 85.1 +/- 13.6 kg). Four treatments were performed in each proband (days 1, 2, 4 and 7). Plasma fibrinogen concentration was lowered from 221.1 +/- 39.0 to 123.5 +/- 21.7 mg/dl (2275 +/- 477 ml plasma treated) by the first treatment, from 172.8 +/- 42.3 to 105.6 +/- 16.5 mg/dl (1609 +/- 761 ml) by the second, from 140.5 +/- 13.8 to 98.8 +/- 8.6 mg/dl (1224 +/- 118 ml) by the third and from 160.2 +/- 23.6 to 106.4 +/- 9.7 mg/dl (1513 +/- 521) by the fourth. Plasma viscosity was improved from 1.40 +/- 0.18 mPa s before the first treatment to 1.23 +/- 0.06 mPa s after fourth treatment, whole blood viscosity from 4.49 +/- 0.36 mPa s to 3.83 +/- 0.27 mPa s (P < 0.01). No clinical side effects and no clinically relevant change of laboratory parameters including in vitro tests on thrombocyte function were observed. Seven men and three women (48-75 years old, 9 patients suffered from diabetes mellitus, one patient from peripheral arterial occlusive disease, 5 patients were on regular hemodialysis) were treated by fibrinogen adsorption. Each column contained 135 ml of coupled sepharose CL-4B. Treatments were scheduled on day 1, 2, 4, 6, 8, 10, 13, 16, 19, 22, 25 and 28. 144 treatments with fibrinogen adsorption were performed. No clinical side effects due to the fibrinogen-adsorption procedure were observed. In these 10 patients the fibrinogen concentration before the first treatment was 473.7 +/- 183.7 mg/dl. In the first treatment session it was lowered to 241.4 +/- 125.8 mg/dl by treating 4270 +/- 1180 ml of plasma. In the following 134 treatments the pre-treatment concentration of fibrinogen was 262.6 +/- 83.4 mg/dl, the post-treatment concentration was 120.6 +/- 37.2 mg/dl. The mean volume of plasma treated was 3737 +/- 1643 ml, the mean duration of a treatment session (except the first treatment) was 143.7 +/- 63.1 min. In 7 patients a mean post-treatment fibrinogen concentration of < or = 123 mg/dl was obtained, in the other patients 133, 177 and 184 mg/dl. Yet, the decrease of fibrinogen concentration was also pronounced in these 3 patients: -82%, -67%, and -73%, respectively. Accelerated wound healing was observed in 9 of the 10 patients. In conclusion, affinity chromatography using the pentapeptide gly-pro-arg-pro-lys is an effective, selective and safe procedure to lower fibrinogen concentration in plasma thereby improving blood viscosity. It could be a therapeutic option in severe blood vessel disease where drug therapy is not sufficient and invasive procedures like bypass or angioplasty cannot be applied.

Elevation of von Willebrand factor in plasma in diabetic patients with neuropathic foot ulceration.

AIMS: The present study examines the relationship between markers of endothelial dysfunction and diabetic neuropathy or consequent neuropathic foot ulceration in patients with Type 2 diabetes mellitus. METHODS: We studied 65 Type 2 diabetic patients including 25 diabetic patients without neuropathy, 27 with neuropathy but no history of foot ulceration, and 13 with neuropathic ulceration. Plasma concentrations of von Willebrand factor (vWF) and soluble thrombomodulin (TM), measures of endothelial dysfunction, were determined by enzyme immunoassays. We performed various tests quantifying aspects of diabetic neuropathy including vibration perception threshold (VPT; for sensory neuropathy), coefficient of variation of R-R intervals (CVR-R; for cardiac autonomic neuropathy), and cold-induced vasodilation in the great toe for peripheral sympathetic neuropathy. RESULTS: CVR-R and cold-induced vasodilation were significantly diminished in patients with neuropathic foot ulceration compared with patients with neuropathy but no history of foot ulceration. Plasma vWF concentrations were positively correlated with VPT and cold-induced vasodilation test, and were inversely correlated with CVR-R. Multivariate analysis disclosed that VPT and percentage vasodilation were independent factors for plasma vWF. Plasma vWF was significantly elevated in patients with foot ulceration compared with patients without neuropathy or those with neuropathy but not foot ulceration. However, plasma TM concentrations did not differ between the three groups. CONCLUSIONS: Diabetic patients with neuropathic foot ulceration had severe impairment of cardiac autonomic and peripheral sympathetic nerves. Elevation of vWF in plasma was associated with neuropathic foot ulceration, linking endothelial dysfunction to foot ulceration.

Transcutaneous oxygen pressure as predictive parameter for ulcer healing in endstage vascular patients treated with spinal cord stimulation.

OBJECTIVE AND DESIGN: This study was designed to test the hypothesis that initial TcPO2 helps predict clinical outcome in vascular patients treated with spinal cord stimulation. A randomized-controlled study with one year follow-up was made in 86 Fontaine stage IV patients with endstage peripheral arterial occlusive disease (PAOD) undergoing 21 day intravenous prostaglandin E1 (PGE1) therapy for nonhealing ulcers. MATERIALS AND METHODS: All patients had arteriosclerosis, 13 also diabetes mellitus. Entry criteria included: non-reconstructible PAOD as proven by intra-arterial angiography or patient condition, ankle systolic pressure < 50 mmHg, severe rest pain despite analgetic medication, and presence of nonhealing foot ulcers or dry gangrene. One week after the start of PGE1 therapy, patients were randomized into receiving SCS plus PGE1 (n = 45 patients), or just PGE1 (n = 41 patients). Follow-up examinations were done at 1, 3, 6 and 12 months. BASELINE: There were no significant differences between both groups in the following: age, sex distribution, ischemic skin lesions, risk factors and several key group mean physiological values including ankle systolic pressure, ankle/brachial ratio (ABI) and foot TcPO2. The SCS group had more prior vascular leg surgeries (1.77 vs 1.58 per patient). RESULTS AT 12 MONTHS: There was significantly better total healing of foot ulcers in the SCS-group (69 vs 17%; p < 0.0001). Significantly more SCS-patients achieved an outcome of Fontaine stage II (claudication pain, no rest pain or lesions) (40 vs 10%, p = 0.0014). The frequency of minor and major amputations was not different, respectively 13 vs 15% and 16 vs 20%. The mean ABI at 12 months of the treated limb of the SCS-patients was not significantly greater. Foot TcPO2 increased significantly for the SCS-group (+213 vs -2%; p < 0.0001). Patients in either group whose TcPO2 rose to 26.0 +/- 8.6 mmHg on average were able to heal ulcers or toe amputation wounds. PGE1-patients had temporary TcPO2 elevations of about 33% on average but this was gone by six months. SCS-patients had steady increases in TcPO2, and maintained them at 12 months. Among the SCS-patients, those with baseline TcPO2 < = 10 mmHg had significantly less success at 12 months, this was not observed for the OMT-patients. The regional perfusion index increased significantly, 187 vs 0%; p < 0.001. CONCLUSIONS: Spinal cord stimulation appears to provide a major benefit for lesion improvement in stage IV patients with non-reconstructible PAOD. Patients with an initial TcPO2 > 10 mmHg will respond better to the stimulation therapy. With pain relief and ulcer healing quality of life improved. Effects on limb salvage do not appear.

[Essential cryofibrinogenemia with generalized livedo racemosa]. / Essentielle Kryofibrinogenämie mit generalisierter Livedo racemosa.

A 45-year-old male patient presented with cold-induced generalized livedo reticularis, repeated acral ulcerations and purpura, Raynaud's phenomenon, and peripheral polyneuropathy. The patient also experienced malaise, vertigo, and transient amaurosis whenever he was exposed to low temperatures. Skin biopsies of the livedo reticularis revealed marked dilatation of the small dermal blood vessels and circumscribed leukocytoclastic vasculitis. Essential cryofibrinogenaemia was diagnosed on the basis of detection of this cryoprotein in the chilled blood plasma with increased viscosity. Pulsed therapy with dexamethasone and cyclophosphamide resulted in marked relief of the symptoms, and cryofibrinogen was no longer detectable in the patient's plasma.