Remnant cholesterol as a risk factor for cardiovascular, cancer or other causes mortality: A competing risks analysis.

BACKGROUND AND AIMS: Cardiovascular diseases (CVDis) are leading causes of morbidity and mortality. Even after the introduction of pharmacological therapy to lower Cholesterol, there is still a residual risk that may be ascribed to remnant cholesterol (RC). We aimed, by analyzing two prospective cohort studies, to estimate the effect of RC on risk and hazard of cardiovascular deaths (CVDs), while accounting for competing risks such as cancer (CDs) and other-causes deaths (OCDs). METHODS AND RESULTS: Cohorts were enrolled in 1992 and 2005. Personal data history was recorded. A fasting venous blood sample was obtained, and RC was calculated at baseline. Cause of Death was coded by using ICD-10th version. Follow-up ended on December 31, 2017. Flexible parametric competing-risks models were applied, with age at death as time-axis. In total, 5729 subjects were enrolled. There were 861 (15.1%) deaths: 234 CVDs (27.2%), 245 CDs (28.5%), 271 OCDs (31.5%) and 111 unknown causes of death (12.8%). RC exposure was a strong risk factor only for CVDs (Risk 2.54, 95% Confidence Interval 1.21; 5.34; Trend 1.26 (1.00; 1.58) for ≥1.29 mmol/L). CONCLUSIONS: RC is a strong independent risk factor for cardiovascular mortality. Competing risk analysis is demonstrably a useful tool to disentangle associations among different competing events with a common risk factor.

Strain Pattern on Electrocardiogram Is Associated with Increased Carotid Intima-Media Thickness in Patients with Aortic Valve Stenosis.

BACKGROUND: Coronary artery disease is present in at least 30% of patients with degenerative aortic stenosis (AS). Atherosclerosis also performs an important role in the progression of AS, because of the similarities of pathological mechanisms in both conditions. The electrocardiogram (EKG) strain pattern is associated with structural myocardial change and subendocardial ischemia and has been worldwide used as a marker of AS severity. We hypothesized that EKG strain pattern would be a marker of atherosclerosis as well in AS patients. The aim of this study was to associate the presence of EKG strain pattern in AS patients with the carotid intima-media thickness (CIMT). METHODS: Fifty-two consecutive patients referred from the cardiology clinic with moderate or severe AS were included in the study and underwent clinical evaluation, EKG, transthoracic echocardiography, and carotid ultrasonography, following statistical analysis of the results. RESULTS: There was a significant association between left ventricular EKG strain and increased CIMT (P = 0.001). The presence of strain increased the odds of abnormal CIMT (P = 0.004, odds ratio 9.7, 95% confidence interval 2.4-45.0), in a model adjusted for age and clinical diagnosis of systemic arterial hypertension. Additionally, EKG strain was associated with the presence of atherosclerotic plaque in at least one carotid artery (P = 0.011). CONCLUSION: Our results suggest that AS patients with EKG strain pattern should be further investigated for the diagnosis of subclinical atherosclerotic disease.

Validity of malnutrition scores for predicting mortality in chronic hemodialysis patients.

PURPOSE: Malnutrition is a strong predictor of mortality in hemodialysis patients. Several scoring systems for evaluating nutritional status have been proposed. However, they rely on different sets of anthropometric and laboratory markers to make a diagnosis of malnutrition and assess its impact on prognosis. To validate them, nutritional scores should be compared with clinical outcomes. Thus, the purpose of this study was to assess malnutrition by three different nutrition scoring systems and determine which best predicts mortality in hemodialysis patients. METHODS: This prospective study included 106 adult chronic hemodialysis patients. Their mean age was 56.3 ± 14.9 years and mean body mass index 24.8 (21.8-28.9); 52 % were men and they had been on dialysis for 24 (5-55) months. Nutritional status was classified according to the diagnostic systems proposed by Wolfson et al. (Am J Clin Nutr 39(4):547-555, 1984), International Society of Renal Nutrition and Metabolism (ISRNM) (Fouque et al. in Kidney Int 73(4):391-398, 2008), and Beberashvili et al. (Nephrol Dial Transplant 25(8):2662-2671, 2010). During about 2 years of follow-up, mortality was assessed by Kaplan-Meier curves, log-rank, and Cox's models adjusted for diabetes, sex, C-reactive protein, time on dialysis, age, and fractional urea clearance. RESULTS: Twenty-three deaths (21.5 %) occurred during the study period. According to the systems of Wolfson, Beberashvili, and the ISRNM, 54, 32, and 20 % of patients, respectively, had malnutrition. Both univariate and multivariate analyses showed that the ISRNM system was the only one that predicted poorer survival (fourfold higher death risk) in malnourished patients. CONCLUSIONS: The scoring system proposed by the ISRNM most accurately identifies patients at higher risk of death.

Asociación del sexo con el estado de salud en respuesta a la oxigenoterapia crónica domiciliaria en pacientes con enfermedad pulmonar obstructiva crónica / Gender and Health Status Response to Long-Term Oxygen Therapy in COPD patients

Introducción: En la enfermedad pulmonar obstructiva crónica (EPOC)muygrave no está clara la asociacióndel sexo con el estado de salud (ES) en respuesta a la oxigenoterapia crónica domiciliaria (OCD). Losobjetivos del presente estudio fueron: 1) comparar la percepción de la disnea y del ES entre hombresy mujeres con EPOC muy grave en el período basal, y 2) proporcionar una evaluación prospectiva de larespuesta del estado de salud a la OCD, de acuerdo con el sexo.Pacientes y métodos: En un estudio longitudinal, prospectivo, se incluyeron pacientes con EPOC hipoxémica(n = 97, edad: 65,5±9,6 años, 53% de hombres) durante 12 meses o hasta su muerte. Se evaluaroncon el Cuestionario Respiratorio de St George (St. George’s Respiratory Questionnaire [SGRQ]) y el índicede disnea basal (IDB).Resultados: En el período basal, el deterioro del ES y la sensación de disnea fueron similares entre ambossexos. Después de 12 meses de OCD, en mujeres se detectó una mejoría de los síntomas (64,1±20,6 frentea 40,6±22,9; p < 0,0001) y de las puntuaciones totales obtenidas en el SGRQ. En hombres también sedemostró una mejoría de los síntomas después de 12 meses (62,7±23,3 frente a 49,6±22,8; p < 0,0005);sin embargo, presentaron un deterioro de las puntuaciones de la esfera de actividad, impacto y totalesdurante el período de estudio, con un declive destacado en la esfera de actividad (68,5±20,0 frentea 75,9±16,9; p = 0,008). Para el IDB no se demostraron diferencias significativas por sexos durante elperíodo del estudio.Conclusiones: Los resultados del presente estudio demuestran que, en pacientes con EPOC muy grave, elcurso del estado de salud difiere de acuerdo con el sexo, puesto que en las mujeres se demuestra unamayor respuesta longitudinal a la OCD(AU)

Introduction: The association of gender with health status (HS) response to long-term oxygen therapy(LTOT) in very severe COPD is unclear. The aims of this study were: (1) to compare dyspnea perceptionand HS between male and female with very severe COPD at baseline and (2) to provide a prospectiveassessment of HS response to LTOT, according to gender.Patients and methods: Hypoxemic COPD (n = 97, age: 65.5±9.6 years, 53% males) were enrolled in aprospective longitudinal study over 12 months or until death. St. George’s Respiratory Questionnaire(SGRQ) and baseline dyspnea index (BDI) were assessed.Results: At baseline, HS impairment and dyspnea sensation were similar between genders. After 12months of LTOT, women presented improvement in symptom (64.1±20.6 versus 40.6±22.9; P < 0.0001)and total SGRQ scores. Men also showed improvement in symptoms after 12 months (62.7±23.3 versus 49.6±22.8; P < 0.0005); however, they presented deterioration of activity, impact and total scores duringthe study period, with markedly decline of activity domain (68.5±20.0 versus 75.9±16.9; P = 0.008). BDIdid not show significant difference by gender over the study period.Conclusions: Our results show that the HS course in very severe COPD patients differs according to gender,as females show greater response longitudinally to LTOT(AU)

[Gender and health status response to long-term oxygen therapy in COPD patients]. / Asociación del sexo con el estado de salud en respuesta a la oxigenoterapia crónica domiciliaria en pacientes con enfermedad pulmonar obstructiva crónica.

INTRODUCTION: The association of gender with health status (HS) response to long-term oxygen therapy (LTOT) in very severe COPD is unclear. The aims of this study were: (1) to compare dyspnea perception and HS between male and female with very severe COPD at baseline and (2) to provide a prospective assessment of HS response to LTOT, according to gender. PATIENTS AND METHODS: Hypoxemic COPD (n = 97, age: 65.5 ± 9.6 years, 53% males) were enrolled in a prospective longitudinal study over 12 months or until death. St. George's Respiratory Questionnaire (SGRQ) and baseline dyspnea index (BDI) were assessed. RESULTS: At baseline, HS impairment and dyspnea sensation were similar between genders. After 12 months of LTOT, women presented improvement in symptom (64.1 ± 20.6 versus 40.6 ± 22.9; P < 0.0001) and total SGRQ scores. Men also showed improvement in symptoms after 12 months (62.7 ± 23.3 versus 49.6 ± 22.8; P < 0.0005); however, they presented deterioration of activity, impact and total scores during the study period, with markedly decline of activity domain (68.5 ± 20.0 versus 75.9 ± 16.9; P = 0.008). BDI did not show significant difference by gender over the study period. CONCLUSIONS: Our results show that the HS course in very severe COPD patients differs according to gender, as females show greater response longitudinally to LTOT.

Potentially modifiable predictors of mortality in patients treated with long-term oxygen therapy.

INTRODUCTION: Anemia is considered a systemic manifestation of Chronic Obstructive Pulmonary Disease (COPD); however, few studies have described its influence on chronic respiratory failure (CRF) prognosis. We aimed to test the hypotheses that anemia negatively influences survival and also to identify the cut-off points of hematocrit (Htc) and hemoglobin (Hb) associated with higher mortality in CRF patients using long-term oxygen therapy (LTOT). METHODS: One-hundred forty two patients with CRF in use of LTOT were evaluated at baseline and followed for three years or until death. Baseline assessment included identification, diagnosis, body composition, dyspnea, health status (HS), spirometry, arterial blood gases, Hb and Htc. Univariate and Cox proportional hazard models were used to evaluate predictors of mortality. We performed ROC curve to identify the best cut-off point of the variables related to survival to construct the Kaplan-Meier curves. RESULTS: Eight-three patients (58%) died after three years. Baseline values of Hb and Htc were significantly lower in the non-survivors group and both, Htc (HR, 0.96; 95%CI 0.91-0.99; p = 0.04), Hb (HR, 0.86; 95%CI 0.76-0.98; p = 0.02) were selected as predictors of mortality after three years. The cut-off points determined were: the value of HB is < 11 g/dl (sensitivity 95% specificity 85%), Htc ≤ 33% (sensitivity 97% specificity 89%). Other prognostic factors were: male gender, low PaCO(2) and SpO(2), higher dyspnea perception and impairment of HS. CONCLUSIONS: Our study shows that anemia is a predictor of mortality in patients with CRF under LTOT treatment. Although anemia is potentially modifiable, the effects of raising hemoglobin on mortality remain undetermined.

Fatores de risco associados à mortalidade de recém-nascidos de muito baixo peso na cidade de Botucatu, São Paulo, no período 1995-2000 / Risk factors for mortality in very low birth-weight infants in the city of Botucaty, State of São Paulo, during the period 1995-2000

OBJETIVOS: avaliar as práticas assistenciais, a ocorrência de doenças, a mortalidade durante a hospitalização e os fatores associados em recém-nascidos prematuros de muito baixo peso (PT-MBP). MÉTODOS: estudo transversal comparando dois períodos: 1995-1997 e 1998-2000 e envolvendo todos os PT-MBP nascidos vivos (n= 451), em um centro perinatal, em Botucatu, São Paulo, Brasil. Os fatores de risco pré-natal e pós-natal foram submetidos a análise multivariada. RESULTADOS: a mortalidade diminuiu de 36,2 por cento para 29,5 por cento. A sobrevida melhorou e foi superior a 50 por cento a partir de 28 semanas e de 750 g de peso. O uso de corticosteróide antenatal aumentou de 25 por cento para 42 por cento, o surfactante exógeno de 14 por cento para 28 por cento, com redução na incidência e gravidade da síndrome do desconforto respiratório. A regressão logística mostrou que a síndrome do desconforto respiratório grave, Odds ratio=18, e a sepse precoce, Odds ratio=2,8, foram importantes fatores de risco para morte em 1995-1997. No período de 1998-2000, a sepse precoce e tardia, Odds ratio=10,5 e 12, respectivamente, aumentaram o risco de morte. CONCLUSÕES: a melhora na assistência perinatal diminuiu a mortalidade do PT-MBP. O aumento na exposição antenatal ao corticosteróide diminuiu a gravidade da síndrome do desconforto respiratório. Em 1998-2000, a sepse foi o único fator de risco para morte.

OBJECTIVES: to evaluate perinatal care, the incidence of diseases, and mortality during hospitalization and associated risk factors in very low birth-weight infants (VLBW). METHODS: a cross sectional survey comparing two periods: 1995-1997 and 1998-2000, including all live-born VLBW preterm infants (n= 451), delivered at a level III perinatal center in the city of Botucatu, State of São Paulo, Brazil. The antenatal and postnatal risk factors were analyzed using multivariable techniques. RESULTS: mortality decreased from 36.2 percent to 29.5 percent. The survival of infants 750 g, and 28 weeks' gestation improved and was higher than 50 percent. The use of antenatal corticosteroid increased from 25 percent to 42 percent, surfactant therapy from 14 percent to 28 percent, and the incidence and severity of respiratory distress syndrome decreased. Regression analysis showed that severe respiratory distress syndrome (Odds ratio= 18) and early-onset sepsis (Odds ratio=2.8) were important risk factors for death in 1995-1997. During 1998-2000 early- and late-onset sepsis (Odds ratio=10.5 and 12 respectively) increased the risk of death. CONCLUSIONS: the improvement in perinatal care has reduced the mortality of VLBW infants. The increase in antenatal corticosteroid exposure has reduced the severity of respiratory distress syndrome. In 1998-2000, sepsis was the only risk factor associated with death.

Predictors of first-year survival in patients with advanced COPD treated using long-term oxygen therapy.

UNLABELLED: Little evidence-based guidance is available to aid clinicians in determining short-term prognoses in very severe COPD patients. Therefore, the present study was designed to provide a prospective assessment (1) of the mortality rates and (2) whether the baseline measurements may be determinants of 1-year mortality in hypoxemic COPD patients receiving long-term oxygen therapy (LTOT). Seventy-eight clinically stable patients with advanced COPD treated using LTOT were enrolled in a prospective cohort study. OUTCOME VARIABLE: first-year mortality. Baseline measurements: categorical variables: age (<60 or > or = 60 years); gender; body mass index (<20 or > or = 20 kg/m(2)); fat-free mass (FFM) index (<16 [men] and <15 kg/m(2) [women]; baseline dyspnea index (BDI) (< or = 3 or >3); and corticosteroid use. Continuous variables: smoking history; lung function; FFM; fat mass; hemoglobin; hematocrit; arterial blood gases; forearm muscle strength; St. George's Respiratory Questionnaire (SGRQ); and comorbidity score. By the end of 1-year of follow-up, 12 patients (15.4%) had died. Kaplan-Meier curves showed that BDI < or = 3 was the only variable associated with higher mortality. Cox proportional hazards analysis revealed that lower PaO(2) and SpO(2), higher PaCO(2) and SGRQ scores were associated with reduced survival. In the multivariate analysis, BDI remained predictive of mortality (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.31-0.81), as did PaO(2) (HR, 0.49; 95% CI, 0.26-0.95). These data suggest that readily available parameters as dyspnea intensity and hypoxemia severity may be useful in predicting first-year survival rates in advanced COPD patients receiving LTOT.

Immune response to the Rhodococcus equi infection in high and low antibody-producing mice (Selection IV-A).

Rhodococcus equi is a gram-positive, facultative intracellular bacterium which infects macrophages and causes rhodococcal pneumonia and enteritis in foals. Recently, this agent has been recognized as an opportunistic pathogen for immunocompromised humans. Several murine experimental models have been used to study R. equi infection. High (H(IV-A)) and Low (L(IV-A)) antibody (Ab)-producers mice were obtained by bi-directional genetic selections for their ability to produce antibodies against sheep and human erythrocytes (Selection IV-A). These lines maintain their phenotypes of high and low responders also for other antigens than those of selection (multispecific effect). A higher macrophage activity in L(IV-A) mice has been described for several intracellular infectious agents, which could be responsible for their intense macrophage antigens (Ag)-handling and low Ab production. Due to these differences, L(IV-A) mice were found to exhibit a better performance to trigger an effective immune response towards intracellular pathogens. The objective of this work was to characterize the immune response of Selection IV-A against R. equi. H(IV-A) and L(IV-A) mice were infected with 2.0x10(6) CFU of ATCC 33701+R. equi by intravenous route. With regards to bacterial clearance and survival assays, L(IV-A) mice were more resistant than H(IV-A) mice to virulent R. equi. L(IV-A) mice presented a higher hydrogen peroxide (H2O2) and nitric oxide (NO) endogenous production by splenic macrophages than H(IV-A) mice. L(IV-A) expressed the most intense cellular response, available by the Delayed-Type Hypersensitivity (DTH) reaction, which activated macrophages and produced more H2O2 and NO. The three times higher specific antibodies titres in H(IV-A) indicated that Selection IV-A maintained the multispecific effect and the polygenic control of humoral and cellular responses also to R. equi.

Comparison of methods for the identification of coagulase-negative staphylococci

Coagulase-negative staphylococci (CNS) species identification is still difficult for most clinical laboratories. The scheme proposed by Kloos and Schleifer and modified by Bannerman is the reference method used for the identification of staphylococcal species and subspecies; however, this method is relatively laborious for routine use since it requires the utilization of a large number of biochemical tests. The objective of the present study was to compare four methods, i.e., the reference method, the API Staph system (bioMérieux) and two methods modified from the reference method in our laboratory (simplified method and disk method), in the identification of 100 CNS strains. Compared to the reference method, the simplified method and disk method correctly identified 100 and 99 percent of the CNS species, respectively, while this rate was 84 percent for the API Staph system. Inaccurate identification by the API Staph method was observed for Staphylococcus epidermidis (2.2 percent), S. hominis (25 percent), S. haemolyticus (37.5 percent), and S. warneri (47.1 percent). The simplified method using the simple identification scheme proposed in the present study was found to be efficient for all strains tested, with 100 percent sensitivity and specificity and proved to be available alternative for the identification of staphylococci, offering, higher reliability and lower cost than the currently available commercial systems. This method would be very useful in clinical microbiology laboratory, especially in places with limited resources.

Comparison of methods for the identification of coagulase-negative staphylococci.

Coagulase-negative staphylococci (CNS) species identification is still difficult for most clinical laboratories. The scheme proposed by Kloos and Schleifer and modified by Bannerman is the reference method used for the identification of staphylococcal species and subspecies; however, this method is relatively laborious for routine use since it requires the utilization of a large number of biochemical tests. The objective of the present study was to compare four methods, i.e., the reference method, the API Staph system (bioMérieux) and two methods modified from the reference method in our laboratory (simplified method and disk method), in the identification of 100 CNS strains. Compared to the reference method, the simplified method and disk method correctly identified 100 and 99% of the CNS species, respectively, while this rate was 84% for the API Staph system. Inaccurate identification by the API Staph method was observed for Staphylococcus epidermidis (2.2%), S. hominis (25%), S. haemolyticus (37.5%), and S. warneri (47.1%). The simplified method using the simple identification scheme proposed in the present study was found to be efficient for all strains tested, with 100% sensitivity and specificity and proved to be available alternative for the identification of staphylococci, offering, higher reliability and lower cost than the currently available commercial systems. This method would be very useful in clinical microbiology laboratory, especially in places with limited resources.