Validation of the online PREDICT tool in a cohort of early breast cancer in Brazil

PREDICT is a tool designed to estimate the benefits of adjuvant therapy and the overall survival of women with early breast cancer. The model uses clinical, histological, and immunohistochemical variables. This study aimed to evaluate the model's performance in a Brazilian population. We assessed the discrimination and calibration of the PREDICT model to estimate overall survival (OS) in five and ten years of follow-up in a cohort of 873 women with early breast cancer diagnosed from January 2001 to December 2016. A total of 743 patients had estrogen receptor (ER)-positive and 130 had ER-negative tumors. The area under the receiver operating characteristic (ROC) curve (AUC) for discrimination was 0.72 (95%CI: 0.66-0.78) at five years and 0.67 (95%CI: 0.61-0.72) at ten years for women with ER-positive tumors. The AUC was 0.72 (95%CI: 0.62-0.81) at five years and 0.67 (95%CI: 0.54-0.77) at ten years for women with ER-negative tumors. The predicted survival in ER-positive tumors was 91.0% (95%CI: 90.2-91.6%) at five years and 79.3% (95%CI: 77.7-81.0%) at ten years, and the observed survival 90.7% (95%CI: 88.6-92.9%) and 77.2% (95%CI: 73.4-81.4%), respectively. The predicted survival in ER-negative tumors was 84.5% (95%CI: 82.5-86.6%) at five years and 75.0% (95%CI: 71.6-78.5%) at ten years, and the observed survival 76.3% (95%CI: 69.1-84.3%) and 67.9% (95%CI: 58.6-78.6%), respectively. In conclusion, PREDICT was accurate to estimate OS in women with ER-positive tumors and overestimated the OS in women with ER-negative tumors.

Immunohistochemical expression of Drosha is reduced in eutopic and ectopic endometrium of women with adenomyosis

The objective of this study was to evaluate the immunohistochemical expression of Dicer, Drosha, and Exportin-5 in the eutopic and ectopic endometrium of women with adenomyosis. Twenty-two paired ectopic and eutopic endometrium from women with adenomyosis and 10 eutopic endometrium samples from control women undergoing hysterectomy were included in the study. Paraffin-embedded tissue blocks were cut and stained for immunohistochemistry. The percentage of epithelial cells positively marked was identified digitally after an automated slide scanning process. Mann-Whitney test or Wilcoxon signed-rank test was performed for independent and paired groups, respectively. A lower expression of Drosha was observed in the eutopic endometrium of women with adenomyosis than in the eutopic endometrium of women without the disease (69.9±3.4% vs 85.2±2.9%, respectively) (P=0.016; 95%CI: 3.4 to 27.4%). We also detected lower Drosha expression in the ectopic endometrium of women with adenomyosis than in the eutopic endometrium of the same women (59.6±3.2% vs 69.9±3.4%, respectively) (P=0.004; 95%CI: 2.3 to 16.7%). Additionally, we observed a correlation between Drosha expression in the ectopic and paired eutopic endometrium (P=0.034, rho=0.454). No significant difference in Dicer or Exportin expression was observed. Predominant pattern of cytoplasmic staining for the anti-Drosha antibody and both a nuclear and cytoplasmic pattern for the anti-Exportin antibody were observed. Drosha expression was significantly lower in the endometrium of women with adenomyosis compared to the eutopic endometrium of asymptomatic women without the disease. Furthermore, its expression was lower in the ectopic endometrium but correlated to the paired eutopic endometrium.

Obesity and high neutrophil-to-lymphocyte ratio are prognostic factors in non-metastatic breast cancer patients

Obesity has been associated with an increased risk of breast cancer recurrence and death. Some readily available biomarkers associated with systemic inflammation have been receiving attention as potential prognostic indicators in cancer, including neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). This study aimed to explore the correlation between body mass index (BMI) and invasive breast cancer and the association of NLR, PLR, and BMI with breast cancer outcomes. We undertook a retrospective study to evaluate patients treated for breast cancer over 14 years. Clinicopathological data was obtained before receiving any treatment. Of the 1664 patients included with stage I-III, 567 (34%) were obese (BMI≥30 kg/m2). Obese patients had larger tumors compared to non-obese patients. Higher BMI was associated with recurrence and worse survival only in patients with stage I disease. NLR and PLR were classified into high and low level groups. The NLRhigh (NLR>4) was found to be an independent prognostic factor for recurrence and mortality, while the PLRhigh (PLR>150) group had no impact on survival. A subgroup of patients with NLRhigh and BMIhigh had the worst disease-free survival (P=0.046), breast cancer-specific survival (P<0.001), and overall survival (P=0.006), compared to the other groups. Patients with early-stage breast cancer bearing NLRhigh and BMIhigh had worse outcomes, and this might be explained by the dysfunctional milieu of obesity in adipose tissue and its effects on the immune system. This study highlights the importance of lifestyle measures and the immune system interference with clinical outcomes in the early breast cancer setting.

Reduction of blood nitric oxide levels is associated with clinical improvement of the chronic pelvic pain related to endometriosis

The objective of this prospective study was to determine the plasma levels of nitric oxide (NO) in women with chronic pelvic pain secondary to endometriosis (n=24) and abdominal myofascial pain syndrome (n=16). NO levels were measured in plasma collected before and 1 month after treatment. Pretreatment NO levels (μM) were lower in healthy volunteers (47.0±12.7) than in women with myofascial pain (64.2±5.0, P=0.01) or endometriosis (99.5±12.9, P<0.0001). After treatment, plasma NO levels were reduced only in the endometriosis group (99.5±12.9 vs 61.6±5.9, P=0.002). A correlation between reduction of pain intensity and reduction of NO level was observed in the endometriosis group [correlation = 0.67 (95%CI = 0.35 to 0.85), P<0.0001]. Reduction of NO levels was associated with an increase of pain threshold in this group [correlation = -0.53 (-0.78 to -0.14), P<0.0001]. NO levels appeared elevated in women with chronic pelvic pain diagnosed as secondary to endometriosis, and were directly associated with reduction in pain intensity and increase in pain threshold after treatment. Further studies are needed to investigate the role of NO in the pathophysiology of pain in women with endometriosis and its eventual association with central sensitization.

Pain pressure threshold algometry of the abdominal wall in healthy women

The objective of this study was to determine the inter- and intra-examiner reliability of pain pressure threshold algometry at various points of the abdominal wall of healthy women. Twenty-one healthy women in menacme with a mean age of 28 ± 5.4 years (range: 19-39 years) were included. All volunteers had regular menstrual cycles (27-33 days) and were right-handed and, to the best of our knowledge, none were taking medications at the time of testing. Women with a diagnosis of depression, anxiety or other mood disturbances were excluded. Women with previous abdominal surgery, any pain condition or any evidence of inflammation, hypertension, smoking, alcoholism, or inflammatory disease were also excluded. Pain perception thresholds were assessed with a pressure algometer with digital traction and compression and a measuring capacity for 5 kg. All points were localized by palpation and marked with a felt-tipped pen and each individual was evaluated over a period of 2 days in two consecutive sessions, each session consisting of a set of 14 point measurements repeated twice by two examiners in random sequence. There was no statistically significant difference in the mean pain threshold obtained by the two examiners on 2 diferent days (examiner A: P = 1.00; examiner B: P = 0.75; Wilcoxon matched pairs test). There was excellent/good agreement between examiners for all days and all points. Our results have established baseline values to which future researchers will be able to refer. They show that pressure algometry is a reliable measure for pain perception in the abdominal wall of healthy women.

p.F508del in a heterogeneous cystic fibrosis population from Minas Gerais, Brazil

Cystic fibrosis (CF) is the most common autosomal recessive disease of the Caucasian population. Among the various CF mutations, p.F508del is the most frequent, accounting for two-thirds of the global CF chromosomes, although showing great variability among populations. We have studied 115 unrelated CF patients from a mixed population of Minas Gerais (Brazil). To evaluate part of the DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, blood DNA was obtained and PCR was performed using two pairs of primers that anneal to exons 10 and 24 of the CFTR gene. The PCR product was then submitted to automatic sequencing using the ABI PRISM 310 Genetic Analyzer. The p.F508del mutation was found in 50 (21.7 percent) of 230 unrelated CF alleles. Fifteen (13.0 percent) patients were homozygous for this mutation, while 20 (17.4 percent) were heterozygous; the remaining 80 (69.6 percent) patients did not carry the p.F508del mutation. Exon 24 sequence had no change in 75 (65.2 percent) patients, 21 (18.3 percent) had the sequence variation 4521G/A, 11 (9.6 percent) had a not yet described sequence variation 4407T/A and 8 (7.0 percent) patients had both sequence variations (4521G/A and 4407T/A). The polymorphism 4407T/A results in an amino acid modification from aspartic acid to glutamic acid, which will probably have no function effect in CFTR. This low p.F508del prevalence can be due to the variable ethnic origin of this population from Minas Gerais, which may have a high diversity of CF rare mutations.

Effect of meconium ileus on the clinical prognosis of patients with cystic fibrosis

The objective of the present study was to determine the possible prognostic factors which may explain the difference in the survival of patients with cystic fibrosis (CF) with and without meconium ileus. Over a period of 20 years, 127 patients with CF, whose diagnosis was confirmed by typical clinical characteristics and altered sweat chloride levels, were studied retrospectively. The patients were divided into two groups: group 1 consisted of patients who presented CF and meconium ileus (N = 9), and group 2 consisted of patients with CF without meconium ileus (N = 118). The characteristics studied were based on data obtained upon admission of the patients using a specific protocol. Demographic, clinical, nutritional and laboratory data were obtained. The genotype was determined in 106 patients by PCR. Survival was analyzed using the Kaplan-Meier method. The median follow-up period was 44 months. A statistically significant difference was observed between the groups studied regarding the following variables: age at diagnosis and weight and height z scores. The presence of meconium ileus was associated with an earlier diagnosis; these patients had greater deficits in height and weight at the time of diagnosis and at the end of the study. The estimated probability of survival for patients with CF without meconium ileus was 62 ± 14 percent and for those with meconium ileus 32 ± 18 percent. Patients with CF and meconium ileus presented a poor nutritional status at diagnosis and a lower survival rate compared to the general CF population

Quadro clínico e nutricional de pacientes com fibrose cística: 20 anos de seguimento no HC-UFMG / Clinical and nutritional aspects of a Center of Cystic Fibrosis-HC-UFMG: 20 years of follow-up

OBJETIVOS: A fibrose cística (FC) é a doença genética letal, de herança autossômica recessiva, mais comum entre pacientes de cor branca. O presente estudo foi realizado com o objetivo de identificar o quadro clínico e nutricional à admissäo dos pacientes no Centro de Tratamento de FC do HC-UFMG e avaliar a sobrevida a longo prazo. PACIENTES E MÉTODOS: Em um período de 20 anos, 127 pacientes portadores de FC foram acompanhados longitudinalmente e submetidos a protocolo previamente estabelecido, após confirmaçäo do diagnóstico pelo teste do suo...

Estudo retrospectivo de asmáticos crônicos em serviço de pneumologia / Retrospective study of chronic asthmatics in Pneumology Services

Foram analisados, retrospectivamente, dois grupos de asmáticos: grupo A (50 pacientes) e grupo B (17 pacientes) classificados de acordo com a utilizaçäo ou näo de corticóides, por tempo prolongado, durante o controle ambulatorial. Observou-se que os pacientes do grupo B (uso de corticóide) eram os mais gravemente acometidos, de acordo com a avaliaçäo dos seguintes parâmetros: internamentos mais freqüentes, acompanhamento ambulatorial por período mais longo e necessidade de maior número de medicamentos para controle adequado. O número relativamente alto (25 por cento) de pacientes, utilizando corticóide no controle ambulatorial, ressalta a necessidade de procedimentos mais objetivos, como monitorizaçäo de drogas e avaliaçäo periódica da funçäo pulmonar, dentre outros, como forma de diminuir este índice

Cornea plana. / Cornea plana

Os autores estudam a cornea plana em 5 pacientes da mesma familia. Concluem a existencia de uma transmissao genetica autossomica recessiva. Consideram todos os casos tipicos com "esclerotizacao" da periferia corniana, opacificacao central profunda da cornea, cujos diametros eram normais

"Cor pulmonale" devido a obstrucao cronica das vias aereas na infancia. / Cor pulmonale secondary to chronic obstruction of the airways in childhood

Os autores apresentam um caso de cor pulmonale e insuficiencia cardiaca congestiva, consequentes a obstrucao cronica de vias aereas superiores por hipertrofia de amigdalas e adenoides, bem como, revisao de 58 casos descritos na literatura. Deve ser ressaltada a raridade do caso e a importancia do reconhecimento precoce da sindrome obstrutiva com tratamento imediato para beneficio do paciente

Alergia tuberculinica e cicatriz vacinal em lactentes que tomaram a vacina BCG injetavel quando recem-nascidos. / Tuberculinic allergy and vaccine reaction in infant who had received intradermal BCG vaccine

Foram estudados 392 recem-nascidos que tomaram a vacina BCG injetavel (cepa Moureau-Rio), entre 0 e 30 dias de vida, que completaram o teste tuberculinico PPD RT 23 - 2 UT, cinco a seis meses apos a vacinacao e que nao apresentavam, nesta epoca, nenhum fator de negativacao do teste.Entre 279/392 lactentes que tomaram a vacina preparada ha menos de quatro horas, 12,5% eram nao reatores ao teste e 3l,9% eram reatores fortes (somente 1,8% com papula acima de 15 mm). Entre os 113/392 que tomaram a vacina preparada ha 24 + 4 horas, 36,3% eram nao reatores e somente 16,8% reatores fortes. Em 160 lactentes do primeiro grupo, o diametro medio das papulas tuberculinicas foi de 8,34 +/- 3,38mm, comparado com o das cicatrizes vacinais de 4,80 +/- l,l5mm. O autor discute a validade do teste para o diagnostico futuro da tuberculose em criancas vacinadas com o BCG quando recem-nascidos e as complicacoes da vacina aplicada na dose de 0,l ml, nesta idade