Gender characterization in a large series of Brazilian patients with spondyloarthritis

An increasing number of women have been diagnosed with spondyloarthritis (SpA) in recent decades. While a few studies have analyzed gender as a prognostic factor of the disease, no studies have addressed this matter with a large number of patients in South America, which is a peculiar region due to its genetic heterogeneity. The aim of the present study was to analyze the influence of gender on disease patterns in a large cohort of Brazilian patients with SpA. A prospective study was carried out involving 1,505 patients [1,090 males (72.4%) and 415 females (27.6%)] classified as SpA according to the European Spondyloarthropaties Study Group criteria who attended at 29 reference centers for rheumatology in Brazil. Clinical and demographic variables were recorded and the following disease indices were administered: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Radiologic Index (BASRI), Maastricht Ankylosing Spondylitis Enthesitis Score (MASES), and Ankylosing Spondylitis Quality of Life (ASQoL). Ankylosing spondylitis (AS) was the most frequent disease in the group (65.4%), followed by psoriatic arthritis (18.4%), undifferentiated SpA (6.7%), reactive arthritis (3.3%), arthritis associated to inflammatory bowel disease (3.2%), and juvenile SpA (2.9%). The male-to-female ratio was 2.6:1 for the whole group and 3.6:1 for AS. The females were older (p<0.001) and reported shorter disease duration (p=0.002) than the male patients. The female gender was positively associated to peripheral SpA (p<0.001), upper limb arthritis (p<0.001), dactylitis (p=0.011), psoriasis (p<0.001), nail involvement (p<0.001), and family history of SpA (p=0.045) and negatively associated to pure axial involvement (p< 0.001), lumbar inflammatory pain (p=0.042), radiographic sacroiliitis (p<0.001), and positive HLA-B27 (p=0.001). The number of painful (p<0.001) and swollen (p=0.006) joints was significantly higher in the female gender, who also achieved higher BASDAI (p<0.001), BASFI (p=0.073, trend), MASES (p=0.019), ASQoL (p=0.014), and patient's global assessment (p=0.003) scores, whereas the use of nonsteroidal anti-inflammatory drugs (p<0.001) and biological agents (p=0.003) was less frequent in the female gender. Moreover, BASRI values were significantly lower in females (p<0.001). The female gender comprised one third of SpA patients in this large cohort and exhibited more significant peripheral involvement and less functional disability, despite higher values in disease indices.

CD4+CD25highFoxp3+Cells Increased in the Peritoneal Fluid of Patients with Endometriosis

Problem To evaluate CD4+CD25highFoxp3+ cells and IL-6, IL-10, IL-17, and TGF-beta in the peritoneal fluid of women with endometriosis. Method of study A total of ninety-eight patients were studied: endometriosis (n = 70) and control (n = 28). First, peritoneal fluid lymphocytes were isolated, and CD4+CD25high cells were identified using flow cytometry. Then, RT-PCR was performed to verify Foxp3 expression in these cells. Also, IL-6, IL-10, IL-17, and TGF-beta concentration was determined. Results Of all the lymphocytes in the peritoneal fluid of women with endometriosis, 36.5% (median) were CD4+CD25high compared to only 1.15% (median) in the control group (P < 0.001). Foxp3 expression was similarly elevated in patients with the disease compared to those without (median, 50 versus 5; P < 0.001). IL-6 and TGF-beta were higher in endometriosis group (IL-6: 327.5 pg/mL versus 195.5 pg/mL; TGF-beta: 340 pg/mL versus 171.5 pg/mL; both P < 0.001). IL-10 and IL-17 showed no significant differences between the two groups. Conclusion The peritoneal fluid of patients with endometriosis had a higher percentage of CD4+CD25highFoxp3+ cells and also higher levels of IL-6 and TGF-beta compared to women without the disease. These findings suggest that CD4+CD25highFoxp3+ cells may play a role in the pathogenesis of endometriosis.

Evaluation of CA-125 and soluble CD-23 in patients with pelvic endometriosis: a case-control study

Objective: To evaluate serum concentrations of CA-125 and soluble CD-23 and to correlate them with clinical symptoms, localization and stage of pelvic endometriosis and histological classification of the disease. Methods: Blood samples were collected from 44 women with endometriosis and 58 without endometriosis, during the first three days (1st sample) and during the 7th, 8th and 9th day (2nd sample) of the menstrual cycle. Measurements of CA-125 and soluble CD-23 were performed by ELISA. Mann-Whitney U test was used for age, pain evaluations (visual analog scale) and biomarkers concentrations. Results: Serum levels Of CA-125 were higher in endometriosis patients when compared to the control group during both periods of the menstrual cycle evaluated in the study. This marker was also elevated in women with chronic pelvic pain, deep dyspareunia (2nd sample), dysmenorrhea (both samples) and painful defecation during the menstrual flow (2nd sample). CA-125 concentration was higher in advanced stages of the disease in both samples and also in women with ovarian endometrioma. Concerning CD-23, no statistically significant differences were observed between groups. Conclusion: The concentrations of CA-125 were higher in patients with endometriosis than in patients without the disease. No significantly differences were observed for soluble CD-23 levels between groups.

A comparison of non-HDL and LDL cholesterol goal attainment in a large, multinational patient population: The Lipid Treatment Assessment Project 2

Objective: This study evaluated the success in attaining non-HDL-cholesterol (non-HDL-C) goals in the multinational L-TAP 2 study. Methods: 9955 patients >= 20 years of age with dyslipidemia on stable lipid-lowering therapy were enrolled from nine countries. Results: Success rates for non-HDL-C goals were 86% in low, 70% in moderate, and 52% in high-risk patients (63% overall). In patients with triglycerides of >200 mg/dL success rates for non-HDL-C goals were 35% vs. 69% in those with <= 200 mg/dL (p < 0.0001). Among patients attaining their LDL-C goal, 18% did not attain their non-HDL-C goal. In those with coronary disease and at least two risk factors, only 34% and 30% attained respectively their non-HDL-C and LDL-C goals. Rates of failure in attaining both LDL-C and non-HDL-C goals were highest in Latin America. Conclusions: Non-HDL-C goal attainment lagged behind LDL-C goal attainment; this gap was greatest in higher-risk patients. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

Metabolic syndrome, dyslipidemia, hypertension and type 2 diabetes in youth: from diagnosis to treatment

Overweight and obesity in youth is a worldwide public health problem. Overweight and obesity in childhood and adolescents have a substantial effect upon many systems, resulting in clinical conditions such as metabolic syndrome, early atherosclerosis, dyslipidemia, hypertension and type 2 diabetes (T2D). Obesity and the type of body fat distribution are still the core aspects of insulin resistance and seem to be the physiopathologic links common to metabolic syndrome, cardiovascular disease and T2D. The earlier the appearance of the clustering of risk factors and the higher the time of exposure, the greater will be the chance of developing coronary disease with a more severe endpoint. The age when the event may occur seems to be related to the presence and aggregation of risk factors throughout life.

Metabolic, hemodynamic and structural adjustments to low intensity exercise training in a metabolic syndrome model

Background The increase in fructose consumption is paralleled by a higher incidence of metabolic syndrome, and consequently, cardiovascular disease mortality. We examined the effects of 8 weeks of low intensity exercise training (LET) on metabolic, hemodynamic, ventricular and vascular morphological changes induced by fructose drinking in male rats. Methods Male Wistar rats were divided into (n = 8 each) control (C), sedentary fructose (F) and ET fructose (FT) groups. Fructose-drinking rats received D-fructose (100 g/l). FT rats were assigned to a treadmill training protocol at low intensity (30% of maximal running speed) during 1 h/day, 5 days/week for 8 weeks. Measurements of triglyceride concentrations, white adipose tissue (WAT) and glycemia were carried out together with insulin tolerance test to evaluate metabolic profile. Arterial pressure (AP) signals were directly recorded. Baroreflex sensitivity (BS) was evaluated by the tachycardic and bradycardic responses. Right atria, left ventricle (LV) and ascending aorta were prepared to morphoquantitative analysis. Results LET reduced WAT (−37.7%), triglyceride levels (−33%), systolic AP (−6%), heart weight/body weight (−20.5%), LV (−36%) and aortic (−76%) collagen fibers, aortic intima-media thickness and circumferential wall tension in FT when compared to F rats. Additionally, FT group presented improve of BS, numerical density of atrial natriuretic peptide granules (+42%) and LV capillaries (+25%), as well as the number of elastic lamellae in aorta compared with F group. Conclusions Our data suggest that LET, a widely recommended practice, seems to be particularly effective for preventing metabolic, hemodynamic and morphological disorders triggered by MS.

Escore de cálcio e angiotomografia coronariana na estratificação do risco cardiovascular

A doença cardiovascular representa a principal causa de mortalidade no mundo. A capacidade de identificar, dentre os indivíduos assintomáticos, o subgrupo que apresenta maior risco de desenvolver eventos cardiovasculares no futuro representa uma etapa fundamental em qualquer estratégia voltada para a diminuição da taxas de eventos cardiovasculares. O primeiro passo na estratificação do risco cardiovascular é a utilização dos "escores de risco global", dentre os quais o mais frequentemente utilizado é o escore de Framingham. Entretanto, estudos prévios demonstraram que embora muito úteis, os escores clínicos, quando utilizados isoladamente, apresentam capacidade limitada de estratificação do risco cardiovascular em uma parcela significativa da população. É nesse contexto que o escore de cálcio (EC) coronariano e a angiotomografia das artérias coronárias podem desempenhar papel importante como ferramentas complementares na estratificação de risco dos pacientes assintomáticos. O EC coronariano proporciona importantes informações prognósticas que são incrementais aos escores clínicos baseados nos fatores de risco tradicionais e a outras modalidades diagnósticas, como a dosagem da proteína C reativa, por exemplo. Além disso, o EC também tem o potencial de alterar a conduta e auxiliar no manejo clínico dos pacientes. Já a angiotomografia coronariana proporciona avaliação detalhada da anatomia das artérias coronárias, permitindo visualizar não apenas o lúmen, mas também as paredes arteriais coronarianas. Comparada à coronariografia invasiva convencional, a angiotomografia apresenta excelente acurácia para identificar e, principalmente, excluir a presença de lesões obstrutivas significativas. Adicionalmente, demonstrou-se capaz de proporcionar informações prognósticas incrementais aos fatores de risco tradicionais e ao EC coronariano.

Standard surgical treatment for benign prostatic hyperplasia is safe for patients over 75 years: analysis of 100 cases from a high-volume urologic center

OBJECTIVES: In this study, we aimed to determine the complications of standard surgical treatments among patients over 75 years in a high-volume urologic center. METHODS: We analyzed 100 consecutive patients older than 75 years who had undergone transurethral prostatic resection of the prostate or open prostatectomy for treatment of benign prostatic hyperplasia from January 2008 to March 2010. We analyzed patient age, prostate volume, prostate-specific antigen level, international prostatic symptom score, quality of life score, urinary retention, co-morbidities, surgical technique and satisfaction with treatment. RESULTS: Median age was 79 years. Forty-eight patients had undergone transurethral prostatic resection of the prostate, and 52 had undergone open prostatectomy. The median International Prostatic Symptom Score was 20, the median prostate volume was 83 g, 51% were using an indwelling bladder catheter, and the median prostatespecific antigen level was 5.0 ng/ml. The most common comorbidities were hypertension, diabetes and coronary disease. After a median follow-up period of 17 months, most patients were satisfied. Complications were present in 20% of cases. The most common urological complication was urethral stenosis, followed by bladder neck sclerosis, urinary fistula, late macroscopic hematuria and persistent urinary incontinence. The most common clinical complication was myocardial infarction, followed by acute renal failure requiring dialysis. Incidental carcinoma of the prostate was present in 6% of cases. One case had urothelial bladder cancer. CONCLUSIONS: Standard surgical treatments for benign prostatic hyperplasia are safe and satisfactory among the elderly. Complications are infrequent, and urethral stenosis is the most common. No clinical variable is associated with the occurrence of complications.

Deficient CEBPA DNA binding function in normal karyotype AML patients is associated with favorable prognosis

CCAAT/enhancer binding protein-α (CEBPA) mutations in acute myeloid leukemia (AML) patients with a normal karyotype (NK) confer favorable prognosis, whereas NK-AML patients per se are of intermediate risk. This suggests that blocked CEBPA function characterizes NK-AML with favorable outcome. We determined the prognostic significance of CEBPA DNA binding function by enzyme-linked immunosorbent assay in 105 NK-AML patients. Suppressed CEBPA DNA binding was defined by 21 good-risk AML patients with inv(16) or t(8;21) (both abnormalities targeting CEBPA) and 8 NK-AML patients with dominant-negative CEBPA mutations. NK-AML patients with suppressed CEBPA function showed a better overall survival (P = .0231) and disease-free survival (P = .0069) than patients with conserved CEBPA function. Suppressed CEBPA DNA binding was an independent marker for better overall survival and disease-free survival in a multivariable analysis that included FLT3-ITD, NPM1 and CEBPA mutation status, white blood cell count, age and lactate dehydrogenase. These data indicate that suppressed CEBPA function is associated with favorable prognosis in NK-AML patients.

Haematopoietic stem cell transplantation in Switzerland. Report from the Swiss Transplant Working Group Blood and Marrow Transplantation (STABMT) Registry 1997-2003

In 1997, the Swiss Transplant Working Group Blood and Marrow Transplantation (STABMT) initiated a mandatory national registry for all haematopoietic stem cell transplants (HSCT) in Switzerland. As of 2003, information was collected of 2010 patients with a first HSCT (577 allogeneic (29%) and 1433 autologous (71%) HSCT) and 616 additional re-transplants. This included 1167 male and 843 female patients with a median age of 42.4 years (range 0.2-76.6 years). Main indications were leukaemias (592; 29%) lymphoproliferative disorders (1,061; 53%), solid tumours (295; 15%) and non-malignant disorders (62; 3%). At the time of analysis 1,263 patients were alive (63%), 747 had died (37%). Probability of survival, transplant related mortality or relapse at 5 years was 52%, 21%, 36% for allogeneic and 54%, 5%, 60% for autologous HSCT. Outcome depended on indication, donor type, stem cell source and age of patient. HSCT is an established therapy in Switzerland. These data describe current practice and outcome.

Percutaneous left-ventricular support with the Impella-2.5-assist device in acute cardiogenic shock: results of the Impella-EUROSHOCK-registry

BACKGROUND Acute cardiogenic shock after myocardial infarction is associated with high in-hospital mortality attributable to persisting low-cardiac output. The Impella-EUROSHOCK-registry evaluates the safety and efficacy of the Impella-2.5-percutaneous left-ventricular assist device in patients with cardiogenic shock after acute myocardial infarction. METHODS AND RESULTS This multicenter registry retrospectively included 120 patients (63.6±12.2 years; 81.7% male) with cardiogenic shock from acute myocardial infarction receiving temporary circulatory support with the Impella-2.5-percutaneous left-ventricular assist device. The primary end point evaluated mortality at 30 days. The secondary end point analyzed the change of plasma lactate after the institution of hemodynamic support, and the rate of early major adverse cardiac and cerebrovascular events as well as long-term survival. Thirty-day mortality was 64.2% in the study population. After Impella-2.5-percutaneous left-ventricular assist device implantation, lactate levels decreased from 5.8±5.0 mmol/L to 4.7±5.4 mmol/L (P=0.28) and 2.5±2.6 mmol/L (P=0.023) at 24 and 48 hours, respectively. Early major adverse cardiac and cerebrovascular events were reported in 18 (15%) patients. Major bleeding at the vascular access site, hemolysis, and pericardial tamponade occurred in 34 (28.6%), 9 (7.5%), and 2 (1.7%) patients, respectively. The parameters of age >65 and lactate level >3.8 mmol/L at admission were identified as predictors of 30-day mortality. After 317±526 days of follow-up, survival was 28.3%. CONCLUSIONS In patients with acute cardiogenic shock from acute myocardial infarction, Impella 2.5-treatment is feasible and results in a reduction of lactate levels, suggesting improved organ perfusion. However, 30-day mortality remains high in these patients. This likely reflects the last-resort character of Impella-2.5-application in selected patients with a poor hemodynamic profile and a greater imminent risk of death. Carefully conducted randomized controlled trials are necessary to evaluate the efficacy of Impella-2.5-support in this high-risk patient group.

Treatment evolution in high-risk congenital diaphragmatic hernia: ten years' experience with diaphragmatic agenesis.

OBJECTIVE: The objective of this study was to evaluate the impact of newer therapies on the highest risk patients with congenital diaphragmatic hernia (CDH), those with agenesis of the diaphragm. SUMMARY BACKGROUND DATA: CDH remains a significant cause of neonatal mortality. Many novel therapeutic interventions have been used in these infants. Those children with large defects or agenesis of the diaphragm have the highest mortality and morbidity. METHODS: Twenty centers from 5 countries collected data prospectively on all liveborn infants with CDH over a 10-year period. The treatment and outcomes in these patients were examined. Patients were followed until death or hospital discharge. RESULTS: A total of 1,569 patients with CDH were seen between January 1995 and December 2004 in 20 centers. A total of 218 patients (14%) had diaphragmatic agenesis and underwent repair. The overall survival for all patients was 68%, while survival was 54% in patients with agenesis. When patients with diaphragmatic agenesis from the first 2 years were compared with similar patients from the last 2 years, there was significantly less use of ECMO (75% vs. 52%) and an increased use of inhaled nitric oxide (iNO) (30% vs. 80%). There was a trend toward improved survival in patients with agenesis from 47% in the first 2 years to 59% in the last 2 years. The survivors with diaphragmatic agenesis had prolonged hospital stays compared with patients without agenesis (median, 68 vs. 30 days). For the last 2 years of the study, 36% of the patients with agenesis were discharged on tube feedings and 22% on oxygen therapy. CONCLUSIONS: There has been a change in the management of infants with CDH with less frequent use of ECMO and a greater use of iNO in high-risk patients with a potential improvement in survival. However, the mortality, hospital length of stay, and morbidity in agenesis patients remain significant.

The significant effect of endometriosis on physical, mental and social wellbeing: results from an international cross-sectional survey.

STUDY QUESTION To what extent do the management of endometriosis and the symptoms that remain after treatment affect the quality of life in women with the disease? SUMMARY ANSWER Many women with endometriosis had impaired quality of life and continued to suffer from endometriosis-associated symptoms even though their endometriosis has been managed in tertiary care centres. WHAT IS KNOWN ALREADY The existing literature indicates that quality of life and work productivity is reduced in women with endometriosis. However, most studies have small sample sizes, are treatment related or examine newly diagnosed patients only. STUDY DESIGN, SIZE, DURATION A cross-sectional questionnaire-based survey among 931 women with endometriosis treated in 12 tertiary care centres in 10 countries. PARTICIPANTS/MATERIALS, SETTING, METHODS Women diagnosed with endometriosis who had at least one contact related to endometriosis-associated symptoms during 2008 with a participating centre were enrolled into the study. The study investigated the effect of endometriosis on education, work and social wellbeing, endometriosis-associated symptoms and health-related quality of life, by using questions obtained from the World Endometriosis Research Foundation (WERF) GSWH instrument (designed and validated for the WERF Global Study on Women's Health) and the Short Form 36 version 2 (SF-36v2). MAIN RESULTS AND THE ROLE OF CHANCE Of 3216 women invited to participate in the study, 1450 (45%) provided informed consent and out of these, 931 (931/3216 = 29%) returned the questionnaires. Endometriosis had affected work in 51% of the women and affected relationships in 50% of the women at some time during their life. Dysmenorrhoea was reported by 59%, dyspareunia by 56% and chronic pelvic pain by 60% of women. Quality of life was decreased in all eight dimensions of the SF-36v2 compared with norm-based scores from a general US population (all P < 0.01). Multivariate regression analysis showed that number of co-morbidities, chronic pain and dyspareunia had an independent negative effect on both the physical and mental component of the SF-36v2. LIMITATIONS, REASONS FOR CAUTION The fact that women were enrolled in tertiary care centres could lead to a possible over-representation of women with moderate-to-severe endometriosis, because the participating centres typically treat more complex and referred cases of endometriosis. The response rate was relatively low. Since there was no Institute Review Board approval to do a non-responder investigation on basic characteristics, some uncertainty remains regarding the representativeness of the investigated population. WIDER IMPLICATIONS OF THE FINDINGS This international multicentre survey represents a large group of women with endometriosis, in all phases of the disease, which increases the generalizability of the data. Women still suffer from frequent symptoms, despite tertiary care management, in particular chronic pain and dyspareunia. As a result their quality of life is significantly decreased. A patient-centred approach with extensive collaboration across disciplines, such as pain specialists, psychologists, sexologists and social workers, may be a valuable strategy to improve the long-term care of women with endometriosis. STUDY FUNDING/COMPETING INTEREST(S) The WERF EndoCost study is funded by the World Endometriosis Research Foundation (WERF) through grants received from Bayer Schering Pharma AG, Takeda Italia Farmaceutici SpA, Pfizer Ltd and the European Society of Human Reproduction and Embryology. The sponsors did not have a role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript. L.H. is the chief executive and T.D. was a board member of WERF at the time of funding. T.D. holds the Merck-Serono Chair in Reproductive Medicine and Surgery, and the Ferring Chair in Reproductive Medicine at the Katholieke Universiteit Leuven in Belgium and has served as consultant/research collaborator for Merck-Serono, Schering-Plough, Astellas and Arresto.

Cardiac medication during pregnancy, data from the ROPAC

BACKGROUND Data on pharmacological management during pregnancy are scarce. The aim of this study was to describe the type and frequency of cardiac medication used in pregnancy in patients with cardiovascular disease and to assess the relationship between medication use and fetal outcome. METHODS AND RESULTS Between 2007 and 2011 sixty hospitals in 28 countries enrolled 1321 pregnant women. All patients had structural heart disease (congenital 66%, valvular 25% or cardiomyopathy 7% or ischemic 2%). Medication was used by 424 patients (32%) at some time during pregnancy: 22% used beta-blockers, 8% antiplatelet agents, 7% diuretics, 2.8% ACE inhibitors and 0.5% statins. Compared to those who did not take medication, patients taking medication were older, more likely to be parous, have valvular heart disease and were less often in sinus rhythm. The odds ratio of fetal adverse events in users versus non-users of medication was 2.6 (95% CI 2.0-3.4) and after adjustment for cardiac and obstetric parameter was 2.0 (95% CI 1.4-2.7). Babies of patients treated with beta-blockers had a significantly lower adjusted birth weight (3140 versus 3240 g, p = 0.002). The highest rate of fetal malformation was found in patients taking ACE inhibitors (8%). CONCLUSION One third of pregnant women with heart disease used cardiac medication during their pregnancy, which was associated with an increased rate of adverse fetal events. Birth weight was significantly lower in children of patients taking beta-blockers. A randomized trial is needed to distinguish the effects of the medication from the effects of the underlying maternal cardiac condition.

Is postmenopausal hormone replacement therapy suitable after a cardio- or cerebrovascular event?

PURPOSE Vascular disease is the leading cause of death in women. One-third of acute events affect women below age 60, when the prevalence of menopausal symptoms is high. This raises the question if hormone replacement therapy (HRT) may be an appropriate treatment for individual women although vascular disease is generally considered a contraindication. METHODS Selective literature search was used for this study. RESULTS In healthy women, HRT increases risks for venous thromboembolism and ischemic stroke, but for cardiovascular disease apparently only beyond 10 years after menopause or 60 years of age. Limited data in women with cardio or cerebrovascular disease have not demonstrated an increased risk for a vascular recurrent event, but for the first year after initiation. In HRT users affected by a cardiovascular event continuation of HRT has not been found to be associated with adverse outcome. Low dose estradiol--preferentially as transdermal patches, if necessary combined with metabolically neutral progestins--appears to convey lower risk. CONCLUSIONS Safety data on HRT in survivors of cardiovascular events or ischemic stroke are limited, but exceptionally increased risk appears to be excluded. If off-label use of HRT is considered to be initiated or continued in women with cardio- or cerebrovascular disease, extensive counseling on the pros and cons of HRT is mandatory.