Elizabeth João Pavin

Comparison of three systems of classification in predicting the outcome of diabetic foot ulcers in a Brazilian population

OBJECTIVE The aim was to compare three ulcer classification systems as predictors of the outcome of diabetic foot ulcers: the Wagner, the University of Texas (UT) and the size (area, depth), sepsis, arteriopathy, denervation system (S(AD)SAD) systems in a specialist clinic in Brazil. METHODS Ulcer area, depth, appearance, infection and associated ischaemia and neuropathy were recorded in a consecutive series of 94 subjects. A novel score, the S(AD)SAD score, was derived from the sum of individual items of the S(AD)SAD system, and was evaluated. Follow-up was for at least 6 months. The primary outcome measure was the incidence of healing. RESULTS Mean age was 57.6 years; 57 (60.6%) were male. Forty-eight ulcers (51.1%) healed without surgery; 11 (12.2%) subjects underwent minor amputation. Significant differences in terms of healing were observed for depth (P=0.002), infection (P=0.006) and denervation (P=0.002) using the S(AD)SAD system, for UT grade (P=0.002) and stage (P=0.032) and for Wagner grades (P=0.002). Ulcers with an S(AD)SAD score of <or=9 (total possible 15) were 7.6 times more likely to heal than scores >or=10 (P<0.001). CONCLUSIONS All three systems predicted ulcer outcome. The S(AD)SAD score of ulcer severity could represent a useful addition to routine clinical practice. The association between outcome and ulcer depth confirms earlier reports. The association with infection was stronger than that reported from the centres in Europe or North America. The very strong association with neuropathy has only previously been observed in Tanzania. Studies designed to compare the outcome in different countries should adopt systems of classification, which are valid for the populations studied.

Role of ultrasound, clinical and scintigraphyc parameters to predict malignancy in thyroid nodule

BackgroundThis study aimed to evaluate clinical, laboratory, ultrasound (US) and scintigraphyc parameters in thyroid nodule and to develop an auxiliary model for clinical application in the diagnosis of malignancy.MethodsWe assessed 143 patients who were surgically treated at a single center, 65% (93) benign vs. 35% (50) malignant lesions at final histology (1998-2008). The clinical, laboratory, scintigraphyc and US features were compared and a prediction model was designed after the multivariate analysis.ResultsThere were no differences in gender, serum TSH and FT4 levels, thyroid auto-antibodies (TAb), thyroid dysfunction and scintigraphyc results (P = 0.33) between benign and malignant nodule groups. The sonographic study showed differences when the presence of suspected characteristics was found in the nodules of the malignant lesions group, such as: microcalcifications, central flow, border irregularity and hypoechogenicity. After the multivariate analysis the model obtained showed age (>39 years), border irregularity, microcalcifications and nodule size over 2 cm as predictive factors of malignancy, featuring 81.7% of accuracy.ConclusionsThis study confirmed a significant increase of risk for malignancy in patients of over 39 years and with suspicious features at US.

Thyroid imaging reporting and data system score combined with Bethesda system for malignancy risk stratification in thyroid nodules with indeterminate results on cytology

The thyroid imaging reporting and data system (TI‐RADS) was designed to better select patients who had undergone fine‐needle aspiration biopsies (FNABs) with high sensitivity and accuracy. However, the combination of TI‐RADS scores and Bethesda system categories in indeterminate thyroid nodules has not been examined extensively.

Interventions to improve patients' compliance with therapies aimed at lowering glycated hemoglobin (HbA1c) in type 1 diabetes: systematic review and meta-analyses of randomized controlled clinical trials of psychological, telecare, and educational interventions

BackgroundBrazilian records on glycemic control in patients with type 1 diabetes show treatment efficacy. Poor patient adherence to therapeutic proposals influences these results and can be associated with social, psychological, and economic aspects, besides others factors. The aim of this study was to evaluate the efficacy of psychological, telecare, and educational interventions to improve treatment compliance among patients with type 1 diabetes. Compliance was assessed indirectly using reduction of glycated hemoglobin (HbA1c) as the principal outcome measure.MethodsSystematic review and meta-analyses of randomized controlled clinical trials (RCTs) were performed using Medline, Embase, Cochrane and Scopus databases up to April 2015. The following medical subject headings were used: Diabetes Mellitus, Type 1, Patient Compliance or Adherence, Hemoglobin A, glycated, and Randomized Controlled Trial. The principal outcome was change in HbA1c between baseline and follow-up. Where appropriate, trials were combined in meta-analysis using fixed effects models.ResultsFrom 191 articles initially identified, 57 were full text reviewed, and 19 articles met the inclusion criteria providing data from 1782 patients (49.4 % males, age 18 years). The RCTs (2 to 24 months in duration) were divided into four groups according to type of intervention: psychology (seven studies; 818 patients), telecare (six studies; 494 patients); education (five studies; 349 patients), and psychoeducation (one study; 153 patients). All studies reported some type of adherence measurement of the interventions. Decrease in HbA1c was observed after psychology (MD −0.310; 95 % CI, −0.599 to −0.0210, P = 0.035) but not after telecare (MD −0.124 %; 95 % CI, −0.268, 0.020; P = 0.090) or educational (MD −0.001; 95 % CI, −0.202, 0.200; P = 0.990) interventions.ConclusionPsychological approaches to improve adherence to diabetes care treatment modestly reduced HbA1c in patients with type 1 diabetes; telecare and education interventions did not change glycemic control. However, the limited number of studies included as well as their methodological quality should be taken into account.

Delayed Small Intestinal Transit in Patients with Long-Standing Type 1 Diabetes Mellitus: Investigation of the Relationships with Clinical Features, Gastric Emptying, Psychological Distress, and Nutritional Parameters

BACKGROUND Studies on small intestinal transit in type 1 diabetes mellitus have reported contradictory results. This study assessed the orocecal transit time (OCTT) in a group of patients with type 1 diabetes mellitus and its relationships with gastrointestinal symptoms, glycemic control, chronic complications of diabetes, anthropometric indices, gastric emptying, small intestinal bacterial overgrowth (SIBO), and psychological distress. SUBJECTS AND METHODS Twenty-eight patients with long-standing (>10 years) type 1 diabetes mellitus (22 women, six men; mean age, 39 ± 9 years) participated in the study. The lactulose hydrogen breath test was used to determine OCTT and the occurrence of SIBO. The presence of anxiety and depression was assessed by the Hospital Anxiety and Depression scale. Gastric emptying was measured by scintigraphy. Anthropometric indices included body mass index, percentage body fat, midarm circumference, and arm muscle area. RESULTS There was a statistically significant increase in OCTT values in diabetes patients (79 ± 41 min) in comparison with controls (54 ± 17 min) (P=0.01). Individual analysis showed that OCTT was above the upper limit (mean+2 SD) in 30.8% of patients. All anthropometric parameters were significantly decreased (P<0.05) in patients with prolonged OCTT in comparison with those with normal OCTT. In contrast, there was no statistically significant association between prolonged OCTT and gastrointestinal symptoms, peripheral neuropathy, diabetic retinopathy, glycated hemoglobin, delayed gastric emptying, SIBO, anxiety, or depression. CONCLUSIONS Small bowel transit may be delayed in about one-third of patients with long-standing type 1 diabetes mellitus. This abnormality seems to have a negative effect on nutritional status in these patients.

Association of genetic variants in the promoter region of genes encoding p22phox (CYBA) and glutamate cysteine ligase catalytic subunit (GCLC) and renal disease in patients with type 1 diabetes mellitus

BackgroundOxidative stress is recognized as a major pathogenic factor of cellular damage caused by hyperglycemia. NOX/NADPH oxidases generate reactive oxygen species and NOX1, NOX2 and NOX4 isoforms are expressed in kidney and require association with subunit p22phox (encoded by the CYBA gene). Increased expression of p22phox was described in animal models of diabetic nephropathy. In the opposite direction, glutathione is one of the main endogenous antioxidants whose plasmatic concentrations were reported to be reduced in diabetes patients. The aim of the present investigation was to test whether functional single nucleotide polymorphisms (SNPs) in genes involved in the generation of NADPH-dependent O2•- (-675 T → A in CYBA, unregistered) and in glutathione metabolism (-129 C → T in GCLC [rs17883901] and -65 T → C in GPX3 [rs8177412]) confer susceptibility to renal disease in type 1 diabetes patients.Methods401 patients were sorted into two groups according to the presence (n = 104) or absence (n = 196) of overt diabetic nephropathy or according to glomerular filtration rate (GFR) estimated by Modification of Diet in Renal Disease (MDRD) equation: ≥ 60 mL (n = 265) or < 60 mL/min/1.73 m2 (n = 136) and were genotyped.ResultsNo differences were found in the frequency of genotypes between diabetic and non-diabetic subjects. The frequency of GFR < 60 mL/min was significantly lower in the group of patients carrying CYBA genotypes T/A+A/A (18.7%) than in the group carrying the T/T genotype (35.3%) (P = 0.0143) and the frequency of GFR < 60 mL/min was significantly higher in the group of patients carrying GCLC genotypes C/T+T/T (47.1%) than in the group carrying the C/C genotype (31.1%) (p = 0.0082). Logistic regression analysis identified the presence of at least one A allele of the CYBA SNP as an independent protection factor against decreased GFR (OR = 0.38, CI95% 0.14-0.88, p = 0.0354) and the presence of at least one T allele of the GCLC rs17883901 SNP as an independent risk factor for decreased GFR (OR = 2.40, CI95% 1.27-4.56, p = 0.0068).ConclusionsThe functional SNPs CYBA -675 T → A and GCLC rs17883901, probably associated with cellular redox imbalances, modulate the risk for renal disease in the studied population of type 1 diabetes patients and require validation in additional cohorts.

Value of Ultrasound and Cytological Classification System to Predict the Malignancy of Thyroid Nodules with Indeterminate Cytology

Although fine-needle aspiration cytology is considered the gold standard for evaluating thyroid nodules, in about 10–30% of the cases, cytology is indeterminate. This study aimed to determine the value of cytological classification system and ultrasound (US) to predict malignancy in indeterminate thyroid nodule. This retrospective analysis enrolled 80 patients surgically treated at a single center, 75% (60) with benign vs. 25% (20) with malignant lesions at final histology. The clinical, scintigraphic, sonographic, and cytological classification (Bethesda) variables were analyzed in these selected cases of indeterminate cytology, and a prediction model was designed after the multivariate analysis. There was a 25% prevalence of malignancy (20/80). There were no differences in gender, serum thyroid-stimulating hormone and FT4 levels, thyroid auto-antibodies, thyroid dysfunction, and scintigraphic results between benign and malignant nodule groups. The border irregularity in sonographic study was at increased risk for malignancy. The cytological analysis based on Bethesda System (category IV) was an independent predictor for malignancy in indeterminate thyroid nodules. After the multivariate analysis, the model obtained showed border irregularity and Bethesda System category IV as predictive factors of malignancy in indeterminate thyroid nodules, featuring 76.9% of accuracy. This study confirmed a significant increase of risk for malignancy in thyroid nodules with indeterminate cytology showing Bethesda System category IV and suspicious features at US. These findings enhance our current limited predictive armamentarium and can be used to guide surgical decision making.

Primary thyroid tuberculosis: a rare etiology of hypothyroidism and anterior cervical mass mimicking carcinoma

OBJECTIVE The involvement of the thyroid by tuberculosis (TB) is rare. Hypothyroidism caused by tissue destruction is an extremely rare report. Our aim was to report a patient with primary thyroid TB emphasizing the importance of diagnosis, despite the rarity of the occurrence. CASE REPORT Women, 62 years old, showing extensive cervical mass since four months, referring lack of appetite, weight loss, dysphagia and dysphonia. Laboratorial investigation revealed primary hypothyroidism. Cervical ultrasound: expansive lesion in left thyroid lobe, involving adjacent muscle. Computed tomography scan: 13 cm diameter cervical mass with central necrosis. Fine needle biopsy: hemorrhagic material. SURGERY total thyroidectomy, left radical neck dissection and protective tracheotomy. The pathological examination showed chronic granulomatous inflammatory process with areas of caseous necrosis and lymph node involvement. The thyroid baciloscopy was positive. Pulmonary disease was absent. The patient was treated with antituberculosis drugs. CONCLUSIONS Thyroid TB is not frequent, and should be considered as differential diagnosis of hypothyroidism and anterior cervical mass.

Virus C genotype predisposes to primary hypothyroidism during interferon-α treatment for chronic hepatitis C.

OBJECTIVE The treatment of the chronic hepatitis C (HCV) with α-interferon is associated with thyroid dysfunction (TD). The aim of this study was to evaluate thyroid function outcome among patients with chronic HCV under treatment with conventional interferon (IFN) or peguilated interferon (PEG-IFN) in association with ribavirin. PATIENTS AND METHODS We studied 293 patients with chronic HCV, submitted to drug therapy for 24 or 48 weeks. Initially, we evaluated FT4, TSH, TPOAb, TgAb, and continued to monitor FT4 and TSH every three months during therapy and six months thereafter. RESULTS At baseline, TD prevalence was 6.82% (n = 20); 6.14% hypothyroidism; 0.68% hyperthyroidism. TPOAb was present in 5.46% of euthyroid patients. Out of 273 euthyroid patients at baseline, 19% developed TD: 17.2% hypothyroidism; 1.8% hyperthyroidism; 5.1% destructive thyroiditis (DT). 90% of TPOAb-positive patients at baseline developed hypothyroidism vs 14.5% of TPOAb-negative patients (p < 0.001). On average, TD occurred after 25.8 ± 15.5 weeks of treatment. 87.2% of patients who developed hypothyroidism did so during the first therapeutic cycle (p = 0.004; OR = 3.52; 95% CI = 1.36-9.65). Patients infected with genotype 1 virus were 2.13 times more likely to develop hypothyroidism (p = 0.036; 95% CI = 1.04-4.38). Hypothyroid and DT patients presented higher TSH levels before-treatment than patients who had remained euthyroid (p < 0.001; p = 0.002, respectively). DT patients presented lower qALT (p = 0.012) than euthyroid patients. CONCLUSION Hypothyroidism was the most frequent TD, especially during the first cycle of α-interferon. Genotype 1 virus was associated with a risk two times higher for developing the illness. There was no need to interrupt or to change HCV treatment. Therefore, approximately 34% of TD was transient.

Linkage disequilibrium with HLA-DRB1-DQB1 haplotypes explains the association of TNF-308G>A variant with type 1 diabetes in a Brazilian cohort

BACKGROUND A functional variant in the promoter region of the gene encoding tumor necrosis factor (TNF; rs1800629, -308G>A) showed to confer susceptibility to T1D. However, TNF rs1800629 was found, in several populations, to be in linkage disequilibrium with HLA susceptibility haplotypes to T1D. We evaluated the association of TNF rs1800629 with T1D in a cohort of Brazilian subjects, and assessed the impact of HLA susceptibility haplotypes in this association. METHODS 659 subjects with T1D and 539 control subjects were genotyped for TNF-308G>A variant. HLA-DRB1 and HLA-DQB1 genes were genotyped in a subset of 313 subjects with T1D and 139 control subjects. RESULTS Associations with T1D were observed for the A-allele of rs1800629 (OR 1.69, 95% CI 1.33-2.15, p<0.0001, in a codominant model) and for 3 HLA haplotypes: DRB1*03:01-DQB1*02:01 (OR 5.37, 95% CI 3.23-8.59, p<0.0001), DRB1*04:01-DQB1*03:02 (OR 2.95, 95% CI 1.21-7.21, p=0.01) and DRB1*04:02-DQB1*03:02 (OR 2.14, 95% CI 1.02-4.50, p=0.04). Linkage disequilibrium was observed between TNF rs1800629 and HLA-DRB1 and HLA-DQB1 alleles. In a stepwise regression analysis HLA haplotypes, but not TNF rs1800629, remained independently associated with T1D. CONCLUSION Our results do not support an independent effect of allelic variations of TNF in the genetic susceptibility to T1D.