Hepatic, Splenic, and Bone Marrow Gaucheromas: A Case Series and Systematic Literature Review.

BACKGROUND AND AIMS: Gaucher disease (GD) is one of the most common lysosomal storage diseases. It is characterized by the accumulation of glucocerebroside lipids in the macrophages, with liver, spleen and bone marrow frequently affected. The affected organs can develop tumor-like lesions (Gaucheromas), which are difficult to diagnose. We present the Gaucheromas and their ultrasonographic characteristics. METHODS: We selected Gaucheromas and their ultrasonographic characteristics found in the last 5 years during the periodical evaluation of 74 adult GD patients in Romania. All the patients had magnetic resonance imaging examination for comparison. A systematic review of all the Gaucheroma-related articles was performed to compare our results with the literature. RESULTS: Gaucheromas were found in 7 adult patients: 4 in the spleen, 2 in the liver and one affecting the bone. No malignancy ultrasound characteristics were found and neither on MRI exams. In the literature, 10 articles reported Gaucheromas, most of them in the liver and spleen in type 1 GD patients. All our patients were also type 1 GD, and the ultrasound aspect did not change during the 5 years follow-up. CONCLUSIONS: Gaucheromas can be found in any patient with GD. Malignancies have to be considered unless proven otherwise. Imaging characterization (ultrasound and MRI) are useful as histopathologic examination is difficult to obtain in all cases.

MBOAT7 rs641738 variant in metabolic-dysfunction-associated fatty liver disease and cardiovascular risk.

Introduction: Although metabolic-dysfunction-associated fatty liver disease (MAFLD) is associated with an increased cardiovascular risk, MAFLD predisposing genetic variants were not steadily related to cardiovascular events. Therefore, we aimed to assess whether membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) rs641738 variant is associated with an increased cardiovascular risk in in MAFLD patients. Methods: We conducted an observational cross-sectional study including 77 subjects (38 MAFLD patients, 39 controls), between January-September 2020 using hepatic ultrasonography and SteatoTestTM to assess hepatic steatosis. Echocardiographic and Doppler ultrasound parameters were evaluated. Genomic DNA was extracted and rs641738 SNP was genotyped using TaqMan assays. Results: The rs641738 variant was not significantly associated with MAFLD, with a p-value of 0.803, 0.5265, 0.9535, and 0.5751 for codominant, dominant, recessive, and overdominant genotypes, respectively. The rs641738 variant overdominant genotype significantly predicted atherosclerotic cardiovascular disease (ASCVD) risk algorithm in univariate analysis (-4.3 [95% CI -8.55 - -0.55, p-value= 0.048]), but lost significance after multivariate analysis (-3.98 [95% CI -7.9 - -0.05, p-value= 0.053]). The rs641738 variant recessive genotype significantly predicted ActiTest in univariate analysis (0.0963 [95% CI 0.0244 - 0.1681, p-value= 0.009]), but lost significance after multivariate analysis (0.0828 [95% CI -0.016 - 0.1816, p-value= 0.105]). Conclusion: No significant association was observed between rs641738 variant and MAFLD in the studied population. The rs641738 variant was found to predict ASCVD risk score and ActiTest in univariate linear regression analysis. However, the significance of both associations was lost after performing multivariate analysis.

The Role of Circulating Collagen Turnover Biomarkers and Late Gadolinium Enhancement in Patients with Non-Ischemic Dilated Cardiomyopathy.

Background: Myocardial scarring is a primary pathogenetic process in nonischemic dilated cardiomyopathy (NIDCM) that is responsible for progressive cardiac remodeling and heart failure, severely impacting the survival of these patients. Although several collagen turnover biomarkers have been associated with myocardial fibrosis, their clinical utility is still limited. Late gadolinium enhancement (LGE) determined by cardiac magnetic resonance imaging (CMR) has become a feasible method to detect myocardial replacement fibrosis. We sought to evaluate the association between collagen turnover biomarkers and replacement myocardial scarring by CMR and, also, to test their ability to predict outcome in conjunction with LGE in patients with NIDCM. Method: We conducted a prospective study on 194 patients (48.7 ± 14.3 years of age; 74% male gender) with NIDCM. The inclusion criteria were similar to those for the definition of NIDCM, performed exclusively by CMR: (1) LV dilation with an LV end-diastolic volume (LVEDV) of over 97 mL/m2; (2) global LV dysfunction, expressed as a decreased LVEF of under 45%. CMR was used to determine the presence and extent of LGE. Several collagen turnover biomarkers were determined at diagnosis, comprising galectin-3 (Gal3), procollagen type I carboxy-terminal pro-peptide (PICP) and N-terminal pro-peptide of procollagen type III (PIIINP). A composite outcome (all-cause mortality, ventricular tachyarrhythmias, heart failure hospitalization) was ascertained over a median of 26 months. Results: Gal3, PICP and PIIINP were considerably increased in those with LGE+ (p < 0.001), also being directly correlated with LGE mass (r2 = 0.42; r2 = 0.44; r2 = 0.31; all p < 0.001). Receiver operating characteristic (ROC) analysis revealed a significant ability to diagnose LGE, with an area under the ROC of 0.816 for Gal3, 0.705 for PICP, and 0.757 for PIIINP (all p < 0.0001). Kaplan−Meier analysis showed that at a threshold of >13.8 ng/dL for Gal3 and >97 ng/dL for PICP, they were able to significantly predict outcome (HR = 2.66, p < 0.001; HR = 1.93, p < 0.002). Of all patients, 17% (n = 33) reached the outcome. In multivariate analysis, after adjustment for covariates, only LGE+ and Gal3+ remained independent predictors for outcome (p = 0.008; p = 0.04). Nonetheless, collagen turnover biomarkers were closely related to HF severity, providing incremental predictive value for severely decreased LVEF of under 30% in patients with NIDCM, beyond that with LGE alone. Conclusions: In patients with NIDCM, circulating collagen turnover biomarkers such as Gal3, PICP and PIIINP are closely related to the presence and extent of LGE and can significantly predict cardiovascular outcome. The joint use of LGE with Gal3 and PICP significantly improved outcome prediction.

Anxiety and Depression in Metabolic-Dysfunction-Associated Fatty Liver Disease and Cardiovascular Risk.

(1) Background: The relationship between anxiety and depression in metabolic-dysfunction-associated fatty liver disease (MAFLD) and cardiovascular (CV) risk remains uncertain. Therefore, we aimed to assess whether anxiety and depression are associated with increased CV risk in MAFLD. (2) Methods: We conducted a cross-sectional observational study involving 77 subjects (39 MAFLD patients, 38 controls), between January and September 2020. Hepatic steatosis was assessed using a combination of hepatic ultrasonography and SteatoTestTM. CV parameters were evaluated using echocardiography and Doppler ultrasound. Self-reported questionnaires pertaining to symptoms of anxiety and depression were used. Anxiety was evaluated using Lehrer Woolfolk Anxiety Symptom Questionnaire (LWASQ), further divided into somatic, behavioral, and cognitive factors, as well as a global score, and depression using Beck Depression Inventory (BDI). (3) Results: MAFLD patients presented significantly higher BDI scores (p-value 0.009) and LWASQ global scores (p-value 0.045) than controls. LWASQ somatic factor was significantly associated with global longitudinal strain (GLS) in linear analysis (-0.0404, p-value = 0.002), while it lost significance following multivariate analysis (-0.0166, p-value = 0.124). Although group (MAFLD vs. controls) predicted BDI, LWASQ global score, and LWASQ somatic factor in linear regression, they lost significance in multivariate analysis. Moreover, the relationship between interventricular septal wall thickness (IVSWT) and BDI, LWASQ global score, and LWASQ somatic factor was significant in linear analysis, but statistical significance disappeared after multivariate analysis. (4) Conclusions: Although MAFLD patients presented increased anxiety and depression risk in univariate analysis, this association lost significance in multivariate analysis. A significant association between GLS levels and LWASQ somatic factor, in addition to IVSWT in anxiety and depression in univariate analysis, was observed, but was lost after multivariate analysis.

Metabolic biomarkers related to cardiac dysfunction in metabolic-dysfunction-associated fatty liver disease: a cross-sectional analysis.

INTRODUCTION: Hepatic steatosis is associated with cardiac systolic and diastolic dysfunction. Therefore, we evaluated metabolites and their potential cardiovascular effects in metabolic-dysfunction-associated fatty liver disease (MAFLD). MATERIALS AND METHODS: We conducted a cross-sectional study involving 75 participants (38 MAFLD and 37 controls). Hepatic steatosis was confirmed by hepatic ultrasonography and SteatoTestTM. Cardiac function was assessed using echocardiography. Metabolomic analysis was conducted using ultra-high-performance liquid chromatography-mass spectrometry. RESULTS: The median age for participants' age was 45 (IQR 30-56.5), with gender distribution of 35 males and 40 females. MAFLD patients had lower levels of glycyl tyrosine (p-value < 0.001), lysophosphatidylcholine (LPC) (18:2/0:0) (p-value < 0.001), LPC (22:6) (p-value < 0.001), and ceramide (Cer) (d18:0/23:0) (p-value 0.003) compared to controls. MAFLD patients presented lower left ventricular ejection fraction (LVEF), E/A ratio, E/e' ratio, and average global longitudinal strain (GLS) values, with a p-value of 0.047, <0.001, 0.008, and <0.001, respectively. Decreased glycyl tyrosine levels were significantly correlated with reduced LVEF, even after performing multiple linear regression with 95% CI (1.34-3.394, p-value < 0.001). Moreover, decreased LPC (18:2/0:0) levels remained significantly associated with E/A ratio, even after adjusting for confounding factors with 95% CI (0.008-0.258, p-value = 0.042). CONCLUSION: MAFLD patients are at risk for developing cardiac systolic and subclinical systolic dysfunctions, as well as diastolic dysfunction. Decreased glycyl tyrosine levels correlate with reduced LVEF and LPC (18:2/0:0) levels with diastolic dysfunction, even after adjusting for confounding factors, suggesting their potential to be used as metabolic biomarkers in detecting cardiovascular risk.

Increased Vascular Endothelial Growth Factor Serum Level and the Role of +936C/T Gene Polymorphism in Chronic Obstructive Pulmonary Disease.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) represents a debilitating disease, with rising morbidity and mortality. Vascular endothelial growth factor (VEGF) plays a major role in angiogenesis, vascular permeability, and airway remodeling. The purpose of this study was to investigate the relationship between VEGF serum levels and VEGF +936 C/T gene polymorphism (rs3025039) with COPD, for the first time in a Romanian population. Materials and Methods: In total, 120 participants from Transylvania were included in this case-control study. Serum levels of VEGF were determined using an enzyme-linked immune-sorbent assay and rs3025039 was investigated by high molecular weight genomic deoxyribonucleic acid (DNA). Spirometric values, arterial blood gas analysis, and the Six Minute Walk Test (6MWT) outcome were also determined. Results: The serum level of VEGF was higher in the COPD group versus controls (p < 0.001), with a positive correlation with the 6MWT outcome. No significant difference was observed in the VEGF serum levels between VEGF +936C/T genotypes. There was no difference in the VEGF +936C/T genotype between COPD patients and healthy subjects (chi2 test p = 0.92, OR = 1.04, 95%CI = 0.41-2.62), but the presence of the T allele was significantly linked to the presence of COPD (chi2 test p = 0.02, OR = 2.36, 95%CI = 1.12-4.97). Conclusions: Higher VEGF serum levels were found in moderate and severe COPD and were positively correlated with the distance in the 6MWT. No significant difference was found between CC, CT, and TT genotypes of rs3025039 and the presence of COPD. The presence of the T allele was found to be linked to COPD and also to the degree of airway obstruction.

Relationship between Adipokines and Cardiovascular Ultrasound Parameters in Metabolic-Dysfunction-Associated Fatty Liver Disease.

(1) Background: The role of adipokines such as adiponectin and visfatin in metabolic-dysfunction-associated fatty liver disease (MAFLD) and cardiovascular disease remains unclear. Therefore, we aim to assess serum adiponectin and visfatin levels in MAFLD patients and associated cardiovascular parameters. (2) Methods: A cross-sectional study involving 80 participants (40 MAFLD patients, 40 controls), recruited between January and September 2020, was conducted, using both hepatic ultrasonography and SteatoTestTM to evaluate hepatic steatosis. Echocardiographic and Doppler parameters were assessed. Serum adipokines were measured using ELISA kits. (3) Results: Adiponectin and visfatin levels were not significantly different in MAFLD vs. controls. Visfatin was associated with mean carotid intima-media thickness (p-value = 0.047), while adiponectin was associated with left ventricular ejection fraction (LVEF) (p-value = 0.039) and E/A ratio (p-value = 0.002) in controls. The association between adiponectin and E/A ratio was significant in the univariate analysis at 95% CI (0.0049-0.1331, p-value = 0.035), but lost significance after the multivariate analysis. Although LVEF was not associated with adiponectin in the univariate analysis, significant values were observed after the multivariate analysis (95% CI (-1.83--0.22, p-value = 0.015)). (4) Conclusions: No significant difference in serum adiponectin and visfatin levels in MAFLD patients vs. controls was found. Interestingly, although adiponectin levels were not associated with LVEF in the univariate analysis, a significant inversely proportional association was observed after the multivariate analysis.

Alveolar proteinosis - an underdiagnosed condition in young people.

Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by an abnormal intra-alveolar accumulation of surfactant derived lipoproteinaceous compounds, leading to dyspnea and, in severe cases, to respiratory failure. The most common form of PAP is the auto-immune one. Secondary PAP has been recognized in myeloid leukemia, non-hematological neoplasms, lung infections or environmental exposure to noxious particles. Mutations in several genes (such as MARS, SFTPB, TTF1) are responsible for the alteration of surfactant production. Diagnosis tools include high-resolution computed tomography, bronchoalveolar lavage. Although over the past 20 years the pathophysiology of PAP has become more clear, the therapeutic strategies still need improvement. A national programme for patients with PAP might be useful in Romania.

Gaucher disease - therapeutic aspects in Romania.

Gaucher disease is a rare autosomal recessive disease caused by the beta-glicosidase activity deficiency, which will lead to substrate accumulation mainly in the liver, spleen or bone marrow. The main symptoms are liver and spleen enlargement, anemia and low platelet count, bone crisis and fatigue. Several treatment options are available, as enzyme replacement therapy, substrate reduction therapy, or chaperones treatment whose effect is still studied. There are 77 adult patients treated at this time in Romania, 54 with intravenous enzyme replacement ant 23 with oral substrate reduction therapy. No severe adverse effects have been reported by now. All patients had improved disease related symptoms after the receiving of the treatment.

Gaucher disease - bone involvement.

Gaucher disease (GD) is a rare genetic disease caused by the enzymatic deficiency of beta-glucocerebrosidase. This will lead to the accumulation of sphingolipids in various organs, such as liver, spleen, bone marrow. Bone involvement is frequent in Gaucher patients, leading to bone pain, necrosis and even fractures or growth deficiency in children, with painful surgeries and progressively decreasing quality of life. The early treatment initiation in symptomatic patients is very important in lowering bone complications frequency and improve general status. We present the case of a young patient whose first manifestation of GD was a bone cystic lesion and the clinical evolution until treatment.

Q10 Coenzyme Supplementation can Improve Oxidative Stress Response to Exercise in Metabolic Syndrome in Rats.

Background: The metabolic syndrome leads to high morbidity and mortality. Almost all pathological states are associated with oxidative stress (OS) disorders. This study evaluates the effects of Coenzyme Q10 (CoQ10) supplementation on different lifestyles, in relation to serum and tissue OS parameters. Materials and methods: Twelve Wistar rat groups (10 rats/group) were equally divided in three types of diets: standard (St), high fat (HF), high sugar (HS); within each diet group there was one sedentary group with CoQ10 supplementation (100 mg/kg body weight), one sedentary without CoQ10, one trained group with CoQ10 and one trained group without CoQ10 supplementation. After 28 days blood samples were collected as follows: after 12 hours of fasting (T0), 1 hour postprandial (T1) and after 1 hour of exercise (T2) or sedentary postprandial time (T3). Thiol groups (SH) and malondialdehyde (MDA) were determined from serum and liver homogenate. Results: Significant changes were observed in fasting MDA for HF (p = 0.024 for training, 0.028 for CoQ10). Postprandial, OS status altered, with highest MDA in HF sedentary non-CoQ10 group (3.92 ± 0.37 vs 2.67 ± 0.41 nmol/ml in St trained CoQ10). At T2 the untrained and non-CoQ10 groups had the highest MDA levels (up to 22.3% vs T1, p < 0.001 in HF) as SH dropped (34.4% decrease vs T1, p < 0.001 in HF). At T3 high MDA levels were observed, correlated with low SH (Pearson r = -0.423 overall), irrespective of the CoQ10 supplementation. CoQ10 improved the liver OS status (MDA and SH decreased), but not the exercise, in all diets. Conclusions: CoQ10 supplementation accompanied by chronic exercise improved the OS serum profile, irrespective of the daily diet. CoQ10 lowered liver MDA and SH concentrations.

Multimodal ultrasound investigation (grey scale, Doppler and 2D-SWE) of salivary and lacrimal glands in healthy people and patients with diabetes mellitus and/or obesity, with or without sialosis.

AIM: To evaluate the ultrasound (US) modifications [grey scale, Doppler, 2D-share wave elastography (2D-SWE)] ofsalivary (parotid and submandibular) and lacrimal glands in healthy people and patients with diabetes mellitus and/or obesity, with or without sialosis. MATERIAL AND METHODS: We evaluated 170 patients (1020 glands, 1700 grey scale and Doppler images), split in two groups (group 1- healthy people, group 2- obese and/or diabetes patients, with or without sialosis). For each patient we assessed the parotid, submandibular and lacrimal glands in grey scale US (echogenicity, homogeneity, glandular contour, posterior border, lymph nodes), color Doppler US and 2D-SWE. All images were analyzed by two examiners blinded to each other or to patients. RESULTS: The interobserver agreement was strong or moderate for all parameters. In group 2, the salivary glands had increased echogenicity, homogeneous aspect and invisible posterior border (all p<0.001). There was no significant variation of elasticity modulus in the groups analyzed (5.46±1.57 vs 5.67±1.81 in parotid, 8.63±1.84 vs 8.55±1.94 in submandibular and 9.47±2.1 vs 9.53±2.23 in lacrimal glands, all p>0.05) or according to the body mass index (BMI), sex, patient age, the aspect in grey scale/Doppler US or the presence of sialosis (all p>0.05). CONCLUSION: The main US differences between healthy people and patients with diabetes mellitus and/or obesity are suggested by the echogenicity, homogeneity, posterior border and the size of glandular area. No significant differences of elasticity modulus were found between the analyzed groups or related to BMI, sex, patient age or other grey scale/Doppler US items analyzed.

Early optic neuropathy during pegylated alfa 2-B interferon and ribavirin HCV treatment. A case report.

INTRODUCTION: Hepatitis C viral infection (HCV) represents an important health problem worldwide. Natural evolution, with its complications, remains a high cause of mortality and morbidity. Interferon (IFN) treatment, along with ribavirin (RBV), was for several years the standard of care. However, many adverse effects have been described during this therapy. We report a very elusive case of optic neuropathy. CASE REPORT: We report the case of a female patient, 50 years old, who underwent pegylated IFN alfa 2B and RBV treatment for viral hepatitis C with low grade fibrosis, in a period when she was not qualified for free oral therapy (with direct acting agents according regulations in this country at that time). After 10 weeks of treatment, she experienced blurred vision and an optic neuropathy was diagnosed, attributed to the HCV. The symptoms and eye fundus alterations (hemorrhage, exudates) remitted after discontinuation of therapy. CONCLUSION: IFN treatment remains an option for viral hepatitis, but the adverse effects are to be considered. Optic neuropathy can occur during the former standard of care HCV therapy. Patients submitted to IFN plus RBV therapy should be monitored for ocular adverse effects.

Acute pancreatitis during GLP-1 receptor agonist treatment. A case report.

Glucagon-like peptide 1 receptor agonists (GLP-1RA) are the newest treatment for diabetes mellitus (DM). These drugs can down-regulate fasting glucose more than oral drugs and lead to more constant glucose levels compared to regular insulin. Acute pancreatitis is a serious condition that may have a fatal outcome. It has been shown that long term and high doses of GLP-1RA can cause pancreatic changes in animals, but no connection has been proven in humans. We present the case of a 67 years old man with DM treated with oral drugs for 10 years until 3 months before, when GLP-1RA was added. He presented progressive abdominal pain, vomiting, and increased level of serum lipase and amylase were found. Ultrasonography and computed tomography found pancreatic and peripancreatic fatty tissue inflammation (inflammation score 2, necrosis score 0). All the etiologies of acute pancreatitis (lithiasis, alcohol, autoimmune, or trauma) were excluded. After GLP-1RA cessation and supportive treatment the evolution was self-limited with full recovery within 5 days. We concluded that acute pancreatitis can be considered a side effect of the GLP-1 treatment.

Brown tumors of the femur and pelvis secondary to a parathyroid carcinoma: report of one case.

Brown tumors result from excess osteoclast activity and consist of collections of osteoclasts intermixed with fibrous tissue and poorly mineralized woven bone. They are secondary to hyperparathyroidism (HPT). Their incidence is higher in primary than in secondary hyperparathyroidism. We report a 69 years-old male, admitted in a state of confusion, lethargy and bedridden, with a pathological fracture of the femur caused by a brown tumor. The laboratory examination revealed a hypercalcemia (8.85 mEq/L), with high levels of ionized Ca (5.48 mEq/L), serum alkaline phosphatases (416 U/L) and serum parathormone (120 pg/mL). Ultrasound examination of the neck showed a large parathyroid tumor, probably corresponding to a carcinoma. A primary HPT was diagnosed. The patient was hydrated and high doses of diuretics and bisphosphonates were administered. After correction of serum calcium and neurologic symptoms, the patient was operated, performing an extensive resection of the tumor. The pathology report confirmed the diagnosis of parathyroid carcinoma.

Brown tumors of the femur and pelvis secondary to a parathyroid carcinoma: Report of one case / Tumores pardos de fémur y pelvis secundarios a carcinoma de paratiroides: Informe de un caso

Brown tumors result from excess osteoclast activity and consist of collections of osteoclasts intermixed with fibrous tissue and poorly mineralized woven bone. They are secondary to hyperparathyroidism (HPT). Their incidence is higher in primary than in secondary hyperparathyroidism. We report a 69 years-old male, admitted in a state of confusion, lethargy and bedridden, with a pathological fracture of the femur caused by a brown tumor. The laboratory examination revealed a hypercalcemia (8.85 mEq/L), with high levels of ionized Ca (5.48mEq/L), serum alkaline phosphatases (416 U/L) and serum parathormone (120 pg/mL). Ultrasound examination of the neck showed a large parathyroid tumor, probably corresponding to a carcinoma. A primary HPT was diagnosed. The patient was hydrated and high doses of diuretics and bisphosphonates were administered. After correction of serum calcium and neurologic symptoms, the patient was operated, performing an extensive resection of the tumor. The pathology report confirmed the diagnosis of parathyroid carcinoma.

Los tumores pardos son una consecuencia de una actividad osteoclástica excesiva y consisten en osteoclastos mezclados con tejido fibroso y tejido óseo mal mineralizado. Son secundarios a hiperparatiroidismo y más comunes en hiperparatiroidismo primario. Informamos de un hombre de 69 años que ingresa confuso y letárgico con una fractura patológica del fémur causada por un tumor pardo. El laboratorio mostró hipercalcemia de 8,85 mEq/L, fosfatasas alcalinas de 416 U/L y parathormona de 120 pg/mL. La ecografía del cuello mostró un tumor paratiroideo sospechoso de carcinoma. Se diagnosticó un hiperparatiroidismo primario. El paciente se hidrató y estabilizó con diuréticos y bifosfonatos. Una vez estabilizado, se operó efectuando una extensa resección del tumor. El estudio anatomopatológico confirmó el diagnóstico de cáncer de paratiroides.

Influence of risk factors and comorbidities on the successful therapy and survival of patients with critical limb ischemia.

BACKGROUND: Critical limb ischemia (CLI) is associated with an increased risk of limb amputation, low quality of life and cardiovascular death. The aim of this study is to identify the prognostic factors of mortality, revascularization failure and amputation failure, as part of risk factors for athero-sclerosis and comorbidities. PATIENTS AND METHODS: We examined 198 patients operated for CLI. Cox analysis was performed to discern the factors that were associated with failure of initial surgical therapy and death. RESULTS: For survival analysis, a significant model emerged with hypertension (p=0.00), cardiac comorbidities (p=0.00), renal comorbidities (p=0.04) and respiratory comorbidities (p=0.02) as significant predictors. Regarding the time to amputation failure, there was a significant model with insulin treated diabetes (p=0.00), coronary artery disease (p=0.02) and cerebrovascular disease (p=0.05) as significant predictors. CONCLUSIONS: Significant predictors for mortality in CLI patients are high risk hypertension, severe coronary artery disease, renal failure requiring dialysis and chronic obstructive pulmonary disease. The association of these prognostic factors results in a proportional decrease of survival. The predictors for amputation failure were, in addition to local factors, insulin treated diabetes, coronary artery disease and cerebrovascular disease. The revascularization for limb salvage depends on the correct indication and accurate surgical technique.