Blood transfusion utilization and recipient survival at Hospital das Clinicas in Sao Paulo, Brazil

BACKGROUND: The characteristics of blood recipients including diagnoses associated with transfusion and posttransfusion survival are unreported in Brazil. The goals of this analysis were: 1) to describe blood utilization according to clinical diagnoses and patient characteristics and 2) to determine the factors associated with survival of blood recipients. STUDY DESIGN AND METHODS: A retrospective cross-sectional analysis was conducted on all inpatients in 2004. Data came from three sources: The first two files consist of data about patient characteristics, clinical diagnosis, and transfusion. Analyses comparing transfused and nontransfused patients were conducted. The third file was used to determine survival recipients up to 3 years after transfusion. Logistic regression was conducted among transfused patients to examine characteristics associated with survival. RESULTS: In 2004, a total of 30,779 patients were admitted, with 3835 (12.4%) transfused. These patients had 10,479 transfusions episodes, consisting of 39,561 transfused components: 16,748 (42%) red blood cells, 15,828 (40%) platelets (PLTs), and 6190 (16%) plasma. The median number of components transfused was three (range, 1-656) per patient admission. Mortality during hospitalization was different for patients whose admissions included transfusion or not (24% vs. 4%). After 1 year, 56% of transfusion recipients were alive. The multivariable model of factors associated with mortality after transfusion showed that the most significant factors in descending order were hospital ward, increasing age, increasing number of components transfused, and type of components received. CONCLUSION: Ward and transfusion are markers of underlying medical conditions and are associated with the probability of survival. PLT transfusions are common and likely reflect the types of patients treated. This comprehensive blood utilization study, the first of its kind in Brazil, can help in developing transfusion policy analyses in South America.

Oral lesions as predictors of highly active antiretroviral therapy failure in Brazilian HIV-infected children

OBJECTIVES: Evaluate the accuracy of HIV-related oral lesions to predict immune and virologic failure on HIV-infected children in use of highly active antiretroviral therapy (HAART). STUDY DESIGN: Data for this cross-sectional analysis come from a longitudinal study being conducted through the HIV-AIDS Outpatient Unit, ENT Division, Hospital das Clinicas, Sao Paulo University Medical School. The study began in January 1990 and is still ongoing. The cut-off point for analyses purposes was December 2004. Subjects were 471 HIV-infected consecutive children attending the outpatient unit during this period, who enrolled regardless of medical or immunological status. The children have undertaken oral cavity examination, serum CD4(+) T-lymphocyte count, and, 271 of them, viral load measurement. Sensitivity, specificity, positive predictive value, negative predictive value and relative risk were calculated. RESULTS: Oral lesions had moderate sensitivity, high specificity and positive predictive value to predict immune failure. It had low sensitivity and positive predictive value, and high specificity to predict virologic failure. DISCUSSION AND CONCLUSIONS: Oral manifestations of HIV can be important markers for immune suppression and for virologic failure, in Brazilian children undergoing HAART.

Revised Diagnostic Criteria for Vogt-Koyanagi-Harada Disease: Considerations on the Different Disease Categories

PURPOSE: To evalulate the applicability of the Revised Diagnostic Criteria for Vogt-Koyanagi-Harada (VKH) disease to Brazilian patients and to verify the association between different disease categories, clinical parameters, and the presence of HLA-DRB1*0405. DESIGN: A retrospective observational case series. METHODS: Medical charts of 67 patients (10 to 64 years in age; 12 men and 55 women), from the Uveitis Service, Hospital das Clinicas, University of Sao Paulo School of Medicine (HCFMUSP), Sao Paulo, Brazil were reviewed. Patients, previously diagnosed with VKH disease using criteria proposed by the American Uveitis Society, underwent retrospective classification based on the Revised Diagnostic Criteria. The degree of concordance was assessed. At presentation, 46 patients (69%) were in the early phase. In this group, the mean time from disease onset to treatment was 15 days (range, one to 30 days). Forty-eight patients (72%) were typed for HLA-DRB1*0405 by polymerase chain reaction-sequence specific primer and polymerase chain reaction,sequence, specific oligonucleotides primer. Disease categories, phase at initial presentation, and ocular complications were analyzed. RESULTS: There was a 100% of concordance between the two criteria. Disease was classified as complete in 10 patients (15%), incomplete in 37 patients (55%), and probable in 20 patients (30%). In each group, respectively, 90%, 76%, and 45% were in the early phase at presentation (P = .017). There was no association between disease categories, the presence of HLA-DRB1*0405, and clinical parameters. CONCLUSION. The Revised Diagnostic Criteria proved useful for diagnosis of VKH disease in Brazilian patients. The present retrospective study did not find any association between disease category and severity parameters. To better understand the relevance of disease categories, a minimum follow-up period to categorize patients should be included in future prospective studies. (Am J Ophthalmol 2009;147:339-345. (C) 2009 by Elsevier Inc. All rights reserved.)

Skeletal muscle major histocompatibility complex class I and II expression differences in adult and juvenile dermatomyositis

OBJECTIVE: To analyze major histocompatibility complex expression in the muscle fibers of juvenile and adult dermatomyositis. METHOD: In total, 28 untreated adult dermatomyositis patients, 28 juvenile dermatomyositis patients (Bohan and Peter's criteria) and a control group consisting of four dystrophic and five Pompe's disease patients were analyzed. Routine histological and immunohistochemical (major histocompatibility complex I and II, StreptoABComplex/HRP, Dakopatts) analyses were performed on serial frozen muscle sections. Inflammatory cells, fiber damage, perifascicular atrophy and increased connective tissue were analyzed relative to the expression of major histocompatibility complexes I and II, which were assessed as negatively or positively stained fibers in 10 fields (200X). RESULTS: The mean ages at disease onset were 42.0 +/- 15.9 and 7.3 +/- 3.4 years in adult and juvenile dermatomyositis, respectively, and the symptom durations before muscle biopsy were similar in both groups. No significant differences were observed regarding gender, ethnicity and frequency of organ involvement, except for higher creatine kinase and lactate dehydrogenase levels in adult dermatomyositis (p<0.050). Moreover, a significantly higher frequency of major histocompatibility complex I (96.4% vs. 50.0%, p<0.001) compared with major histocompatibility complex II expression (14.3% vs. 53.6%, p = 0.004) was observed in juvenile dermatomyositis. Fiber damage (p = 0.006) and increased connective tissue (p<0.001) were significantly higher in adult dermatomyositis compared with the presence of perifascicular atrophy (p<0.001). The results of the histochemical and histological data did not correlate with the demographic data or with the clinical and laboratory features. CONCLUSION: The overexpression of major histocompatibility complex I was an important finding for the diagnosis of both groups, particularly for juvenile dermatomyositis, whereas there was lower levels of expression of major histocompatibility complex II than major histocompatibility complex I. This finding was particularly apparent in juvenile dermatomyositis.

Proteinuria predicts relapse in adolescent and adult minimal change disease

OBJECTIVE: This study sought to outline the clinical and laboratory characteristics of minimal change disease in adolescents and adults and establish the clinical and laboratory characteristics of relapsing and non-relapsing patients. METHODS: We retrospectively evaluated patients with confirmed diagnoses of minimal change disease by renal biopsy from 1979 to 2009; the patients were aged >13 years and had minimum 1-year follow-ups. RESULTS: Sixty-three patients with a median age (at diagnosis) of 34 (23-49) years were studied, including 23 males and 40 females. At diagnosis, eight (12.7%) patients presented with microscopic hematuria, 17 (27%) with hypertension and 17 (27%) with acute kidney injury. After the initial treatment, 55 (87.3%) patients showed complete remission, six (9.5%) showed partial remission and two (3.1%) were nonresponders. Disease relapse was observed in 34 (54%) patients who were initial responders (n = 61). In a comparison between the relapsing patients (n = 34) and the non-relapsing patients (n = 27), only proteinuria at diagnosis showed any significant difference (8.8 (7.1-12.0) vs. 6.0 (3.6-7.3) g/day, respectively, p = 0.001). Proteinuria greater than 7 g/day at the initial screening was associated with relapsing disease. CONCLUSIONS: In conclusion, minimal change disease in adults may sometimes present concurrently with hematuria, hypertension, and acute kidney injury. The relapsing pattern in our patients was associated with basal proteinuria over 7 g/day.

Lean diesel technology and human health: a case study in six Brazilian metropolitan regions

OBJECTIVE: Due to their toxicity, diesel emissions have been submitted to progressively more restrictive regulations in developed countries. However, in Brazil, the implementation of the Cleaner Diesel Technologies policy (Euro IV standards for vehicles produced in 2009 and low-sulfur diesel with 50 ppm of sulfur) was postponed until 2012 without a comprehensive analysis of the effect of this delay on public health parameters. We aimed to evaluate the impact of the delay in implementing the Cleaner Diesel Technologies policy on health indicators and monetary health costs in Brazil. METHODS: The primary estimator of exposure to air pollution was the concentration of ambient fine particulate matter (particles with aerodynamic diameters, <2.5 mu m, [PM2.5]). This parameter was measured daily in six Brazilian metropolitan areas during 2007-2008. We calculated 1) the projected reduction in the PM2.5 that would have been achieved if the Euro IV standards had been implemented in 2009 and 2) the expected reduction after implementation in 2012. The difference between these two time curves was transformed into health outcomes using previous dose-response curves. The economic valuation was performed based on the DALY (disability-adjusted life years) method. RESULTS: The delay in implementing the Cleaner Diesel Technologies policy will result in an estimated excess of 13,984 deaths up to 2040. Health expenditures are projected to be increased by nearly US$ 11.5 billion for the same period. CONCLUSIONS: The present results indicate that a significant health burden will occur because of the postponement in implementing the Cleaner Diesel Technologies policy. These results also reinforce the concept that health effects must be considered when revising fuel and emission policies.

Predicting dysthyroid optic neuropathy using computed tomography volumetric analyses of orbital structures

OBJECTIVE: To evaluate the ability of orbital apex crowding volume measurements calculated with multidetector-computed tomography to detect dysthyroid optic neuropathy. METHODS: Ninety-three patients with Graves' orbitopathy were studied prospectively. All of the patients underwent a complete neuro-ophthalmic examination and computed tomography scanning. Volumetric measurements were calculated from axial and coronal contiguous sections using a dedicated workstation. Orbital fat and muscle volume were estimated on the basis of their attenuation values (in Hounsfield units) using measurements from the anterior orbital rim to the optic foramen. Two indexes of orbital muscle crowding were calculated: i) the volumetric crowding index, which is the ratio between soft tissue (mainly extraocular muscles) and orbital fat volume and is based on axial scans of the entire orbit; and ii) the volumetric orbital apex crowding index, which is the ratio between the extraocular muscles and orbital fat volume and is based on coronal scans of the orbital apex. Two groups of orbits (with and without dysthyroid optic neuropathy) were compared. RESULTS: One hundred and two orbits of 61 patients with Graves' orbitopathy met the inclusion criteria and were analyzed. Forty-one orbits were diagnosed with Graves' orbitopathy, and 61 orbits did not have optic neuropathy. The two groups of orbits differed significantly with regard to both of the volumetric indexes (p<0.001). Although both indexes had good discrimination ability, the volumetric orbital apex crowding index yielded the best results with 92% sensitivity, 86% specificity, 81%/94% positive/negative predictive value and 88% accuracy at a cutoff of 4.14. CONCLUSION: This study found that the orbital volumetric crowding index was a more effective predictor of dysthyroid optic neuropathy than previously described computed tomography indexes were.

Broncoscopia flexível como primeira opção para a remoção de corpo estranho das vias aéreas em adultos

OBJETIVO: Determinar a taxa de sucesso da broncoscopia flexível como primeira opção na remoção de corpos estranhos das vias aéreas em adultos. MÉTODOS: Estudo retrospectivo de todos os pacientes adultos (acima de 18 anos) com aspiração de corpo estranho submetidos a broncoscopia no Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, em São Paulo (SP). RESULTADOS: A amostra foi constituída por 40 pacientes adultos, com média de idade de 52 anos (variação: 18-88 anos). A mediana do tempo de permanência do corpo estranho na via aérea foi de 15 dias (variação: 12 h a 10 anos). Todos os pacientes foram submetidos primeiramente a broncoscopia flexível diagnóstica. A retirada do corpo estranho por meio de broncoscopia flexível foi bem-sucedida em 33 dos pacientes (82,5%). Em 1 paciente, um objeto metálico alojado na árvore brônquica distal requereu o uso de fluoroscopia. Seis pacientes (15%) foram submetidos a broncoscopia rígida devido a dispneia induzida por corpo estranho traqueal, em 2, e porque o corpo estranho era muito grande para as pinças flexíveis, em 4. A broncoscopia falhou em apenas 1 paciente, que portanto necessitou de broncotomia. CONCLUSÕES: Embora a broncoscopia rígida seja considerada o padrão ouro na remoção de corpos estranhos na via aérea, nossa experiência mostrou que a broncoscopia flexível pode ser utilizada segura e eficientemente no diagnóstico e tratamento de pacientes adultos estáveis.

Effects of arterial oxygen tension and cardiac output on venous saturation: a mathematical modeling approach

OBJECTIVES: Hemodynamic support is aimed at providing adequate O-2 delivery to the tissues; most interventions target O-2 delivery increase. Mixed venous O-2 saturation is a frequently used parameter to evaluate the adequacy of O-2 delivery. METHODS: We describe a mathematical model to compare the effects of increasing O-2 delivery on venous oxygen saturation through increases in the inspired O-2 fraction versus increases in cardiac output. The model was created based on the lungs, which were divided into shunted and non-shunted areas, and on seven peripheral compartments, each with normal values of perfusion, optimal oxygen consumption, and critical O-2 extraction rate. O-2 delivery was increased by changing the inspired fraction of oxygen from 0.21 to 1.0 in steps of 0.1 under conditions of low (2.0 L.min(-1)) or normal (6.5 L.min(-1)) cardiac output. The same O-2 delivery values were also obtained by maintaining a fixed O-2 inspired fraction value of 0.21 while changing cardiac output. RESULTS: Venous oxygen saturation was higher when produced through increases in inspired O-2 fraction versus increases in cardiac output, even at the same O-2 delivery and consumption values. Specifically, at high inspired O-2 fractions, the measured O-2 saturation values failed to detect conditions of low oxygen supply. CONCLUSIONS: The mode of O-2 delivery optimization, specifically increases in the fraction of inspired oxygen versus increases in cardiac output, can compromise the capability of the "venous O-2 saturation" parameter to measure the adequacy of oxygen supply. Consequently, venous saturation at high inspired O-2 fractions should be interpreted with caution.

A comparison of CA125, HE4, risk ovarian malignancy algorithm (ROMA), and risk malignancy index (RMI) for the classification of ovarian masses

OBJECTIVE: Differentiation between benign and malignant ovarian neoplasms is essential for creating a system for patient referrals. Therefore, the contributions of the tumor markers CA125 and human epididymis protein 4 (HE4) as well as the risk ovarian malignancy algorithm (ROMA) and risk malignancy index (RMI) values were considered individually and in combination to evaluate their utility for establishing this type of patient referral system. METHODS: Patients who had been diagnosed with ovarian masses through imaging analyses (n = 128) were assessed for their expression of the tumor markers CA125 and HE4. The ROMA and RMI values were also determined. The sensitivity and specificity of each parameter were calculated using receiver operating characteristic curves according to the area under the curve (AUC) for each method. RESULTS: The sensitivities associated with the ability of CA125, HE4, ROMA, or RMI to distinguish between malignant versus benign ovarian masses were 70.4%, 79.6%, 74.1%, and 63%, respectively. Among carcinomas, the sensitivities of CA125, HE4, ROMA (pre-and post-menopausal), and RMI were 93.5%, 87.1%, 80%, 95.2%, and 87.1%, respectively. The most accurate numerical values were obtained with RMI, although the four parameters were shown to be statistically equivalent. CONCLUSION: There were no differences in accuracy between CA125, HE4, ROMA, and RMI for differentiating between types of ovarian masses. RMI had the lowest sensitivity but was the most numerically accurate method. HE4 demonstrated the best overall sensitivity for the evaluation of malignant ovarian tumors and the differential diagnosis of endometriosis. All of the parameters demonstrated increased sensitivity when tumors with low malignancy potential were considered low-risk, which may be used as an acceptable assessment method for referring patients to reference centers.

Increased IgE serum levels are unrelated to allergic and parasitic diseases in patients with juvenile systemic lupus erythematosus

OBJECTIVE: The aim of this study was to assess the IgE serum levels in juvenile systemic lupus erythematosus patients and to evaluate possible associations with clinical and laboratory features, disease activity and tissue damage. METHODS: The IgE serum concentrations in 69 consecutive juvenile systemic lupus erythematosus patients were determined by nephelometry. IgG, IgM and IgA concentrations were measured by immunoturbidimetry. All patients were negative for intestinal parasites. Statistical analysis methods included the Mann-Whitney, chi-square and Fisher's exact tests, as well as the Spearman rank correlation coefficient. RESULTS: Increased IgE concentrations above 100 IU/mL were observed in 31/69 (45%) juvenile systemic lupus erythematosus patients. The mean IgE concentration was 442.0 +/- 163.4 IU/ml (range 3.5- 9936.0 IU/ml). Fifteen of the 69 patients had atopic disease, nine patients had severe sepsis and 56 patients presented with nephritis. The mean IgE level in 54 juvenile systemic lupus erythematosus patients without atopic manifestations was 271.6 +/- 699.5 IU/ml, and only nine of the 31 (29%) patients with high IgE levels had atopic disease. The IgE levels did not statistically differ with respect to the presence of atopic disease, severe sepsis, nephritis, disease activity, or tissue damage. Interestingly, IgE concentrations were inversely correlated with C4 levels ( r = -0.25, p = 0.03) and with the SLICC/ACR-DI score (r = -0.34, p = 0.005). The IgE concentration was also found to be directly correlated with IgA levels (r = 0.52, p = 0.03). CONCLUSIONS: The present study demonstrated for the first time that juvenile systemic lupus erythematosus patients have increased IgE serum levels. This increase in IgE levels was not related to allergic or parasitic diseases. Our results are in line with the hypothesis that high IgE levels can be considered a marker of immune dysregulation.

Noninvasive positive-pressure ventilation in clinical practice at a large university-affiliated Brazilian hospital

OBJECTIVES: To describe noninvasive positive-pressure ventilation use in intensive care unit clinical practice, factors associated with NPPV failure and the associated prognosis. METHODS: A prospective cohort study. RESULTS: Medical disorders (59%) and elective surgery (21%) were the main causes for admission to the intensive care unit. The main indications for the initiation of noninvasive positive-pressure ventilation were the following: post-extubation, acute respiratory failure and use as an adjunctive technique to chest physiotherapy. The noninvasive positive-pressure ventilation failure group was older and had a higher Simplified Acute Physiology Score II score. The noninvasive positive-pressure ventilation failure rate was 35%. The main reasons for intubation were acute respiratory failure (55%) and a decreased level of consciousness (20%). The noninvasive positive-pressure ventilation failure group presented a shorter period of noninvasive positive-pressure ventilation use than the successful group [three (2-5) versus four (3-7) days]; they had lower levels of pH, HCO3 and base excess, and the FiO(2) level was higher. These patients also presented lower PaO2:FiO2 ratios; on the last day of support, the inspiratory positive airway pressure and expiratory positive airway pressure were higher. The failure group also had a longer average duration of stay in the intensive care unit [17 (10-26) days vs. 8 (5-14) days], as well as a higher mortality rate (9 vs. 51%). There was an association between failure and mortality, which had an odds ratio (95% CI) of 10.6 (5.93 - 19.07). The multiple logistic regression analysis using noninvasive positive pressure ventilation failure as a dependent variable found that treatment tended to fail in patients with a Simplified Acute Physiology Score II >= 34, an inspiratory positive airway pressure level >= 15 cmH2O and pH<7.40. CONCLUSION: The indications for noninvasive positive-pressure ventilation were quite varied. The failure group had a longer intensive care unit stay and higher mortality. Simplified Acute Physiology Score II >= 34, pH<7.40 and higher inspiratory positive airway pressure levels were associated with failure.

Hyaluronidase splice variants are associated with histology and outcome in adenocarcinoma and squamous cell carcinoma of the lung

Heterogeneity of hyaluronidase (HYAL) expression has been identified in tumors and shows promise as an indicator of disease progression. The expression profile of alternatively spliced forms of HYAL was evaluated in tumors and normal lung tissue from 69 resected tumors of patients with adenocarcinomas and squamous cell carcinomas. HYAL1-wild-type (wt) and variants 1 to 5, HYAL2-wt, and HYAL3-wt, and variants 1 to 3 were identified by polymerase chain reaction and direct sequencing. Different proportions of the 3 HYAL-wt and variants were expressed in tumor and normal lung tissues. HYAL1-wt was associated with a poorer prognosis and HYAL3-vl with a better prognosis. HYAL splice variants are associated with histology and outcome, suggesting that strategies aimed at modulating their levels may be effective for lung cancer treatment. (C) 2012 Elsevier Inc. All rights reserved.

PIK3CA exon 20 mutations are associated with poor prognosis in breast cancer patients

OBJECTIVES: The phosphatidylinositol 3-kinase/AKT axis is an important cell-signaling pathway that mediates cell proliferation and survival, two biological processes that regulate malignant cell growth. The phosphatidylinositol 3-kinase CA gene encodes the p110 alpha subunit of the phosphatidylinositol 3-kinase protein. There are phosphatidylinositol 3-kinase CA mutations in several types of human tumors, and they are frequently observed in breast cancer. However, these mutations have not been investigated in Brazilian breast cancer patients. METHODS: PCR-SSCP and direct DNA sequencing were performed to identify phosphatidylinositol 3-kinaseCA exon 9 and exon 20 mutations in 86 patients with sporadic breast cancer. The relationships between PIK3CA mutations and patient clinicopathological characteristics and survival were analyzed. The presence of the TP53 mutation was also examined. RESULTS: Twenty-three (27%) of the 86 primary breast tumors contained PIK3CA mutations. In exons 9 and 20, we identified the hotspot mutations E542K, E545K, and H1047R, and we identified two new missense mutations (I1022V and L1028S) and one nonsense (R992X) mutation. Phosphatidylinositol 3-kinase CA exon 20 mutations were associated with poor overall survival and TP53 gene mutations. CONCLUSIONS: Phosphatidylinositol 3-kinase CA mutations are common in tumors in Brazilian breast cancer patients, and phosphatidylinositol 3-kinase CA and TP53 mutations are not mutually exclusive. Phosphatidylinositol 3-kinase CA exon 20 mutations are associated with poor survival, and they may be useful biomarkers for identifying breast cancer patients with aggressive tumors and for predicting the response to treatment with PI3K pathway inhibitors.