Comparing Prognosis for BRCA1, BRCA2, and Non-BRCA Breast Cancer.

BACKGROUND: Germline pathogenic variants (PV) in BRCA1 and BRCA2 genes, which account for 20% of familial breast cancer (BC) cases, are highly penetrant and are associated with Hereditary Breast/Ovarian Cancer Syndrome. Previous studies, mostly including higher numbers of BRCA1 BC patients, yielded conflicting results regarding BRCA1/2 BC outcomes. In the Portuguese population, BRCA2 BC is diagnosed more frequently than BRCA1 BC. We aimed to compare clinicopathological characteristics and prognosis between BC patients with BRCA1 and BRCA2 mutations and a control group without germline PV (BRCA-wt). Furthermore, we explored the frequency and outcomes of risk-reducing surgeries in BRCA-mutated patients. METHODS: Prospective follow-up was proposed for patients with a diagnosed BRCA1/2 PV. For this study, a matched control group (by age at diagnosis, by decade, and by stage at diagnosis) included BC patients without germline PV. We compared overall survival (OS) and invasive disease-free survival (iDFS) within the three groups, and the use of risk-reducing surgeries among the BRCA cohort. RESULTS: For a mean follow-up time of 113.0 months, BRCA-wt patients showed longer time to recurrence (p = 0.002) and longer OS (p < 0.001). Among patients with BRCA mutations, no statistical differences were found, although patients with BRCA2 BC had longer iDFS and OS. Uptake of risk-reducing surgeries (contralateral prophylactic mastectomy and salpingo-oophorectomy) were negative predictors of invasive disease and death, respectively. CONCLUSIONS: Testing positive for a BRCA PV is associated with a higher risk of relapse and death in patients with BC in the Portuguese population. Risk-reducing mastectomy and salpingo-oophorectomy were associated with lower incidence of relapse and longer median iDFS and OS, respectively.

ATM germline variants and male breast cancer.

Male breast cancer is rare and has been frequently associated with cancer predisposing variants, particularly in BRCA 1 and BRCA 2 genes. ATM pathogenic variants may also increase risk for breast and other cancers. However, less than 10 cases relating ATM mutations and male breast cancer have been previously reported. Therefore, risk estimates and surveillance recommendations are not well established. We report a case of a male patient with breast cancer found to be heterozygous for a pathogenic ATM variant after multigene testing. We also review the literature regarding increased cancer risk associated with ATM germline variants, with emphasis on potential recommendations for surveillance and follow-up.

A Case of Brucellosis with Possible Ileal Involvement.

INTRODUCTION: Brucellosis is a zoonotic disease that can involve different organs and tissues. Fever, fatigue, lymphadenopathy, hepatosplenomegaly, cytopenia, and arthritis are the usual modes of presentation. Gastrointestinal manifestations of human brucellosis are common but documented ileal involvement is extremely rare. CASE DESCRIPTION: A 68-year-old female presented with a history of 10 days of intense temporal migraine, photophobia, and phonophobia with partial response to paracetamol. The patient referred night sweats, anorexia, and colicky abdominal pain after her meals for the past 4 months followed by diarrhea. She denied nausea, vomiting, hypersensitivity of the scalp, blurry vision, melena, or rectal bleeding. She denied travelling or contact with animals. Physical examination revealed fever (38.3°C) and splenomegaly. Laboratory workup revealed Hb 7.8 g/dL, leukopenia (3.47 × 109/L), C-reactive protein 5.94 mg/dL, and erythrocyte sedimentation rate 23 mm/h. Abdominal ultrasound showed hepatic steatosis and mild homogeneous splenomegaly. Chest radiography was normal. Lumbar puncture; transcranial, carotid, and temporal arteries Doppler, and head computed tomography (CT) did not show any significant changes. Abdominal CT showed diffuse thickening of the ileum and some mildly swollen locoregional lymph nodes. Fecal calprotectin was not elevated. Blood cultures and serologies were positive for Brucella (positive Rose-Bengal test, ELISA IgM-positive, IgG-negative anti-brucella antibody serology and positive Huddleson reaction - titer 1:320). The patient was started on rifampicin 600 mg/day and doxycycline 100 mg q. 12 h for 10 weeks with good clinical and analytical response. Upper and lower gastrointestinal endoscopy were normal, although the last was done already under antibiotic treatment. DISCUSSION: Although gastrointestinal manifestations of brucellosis are quite common, ileitis is thought to be extremely rare. In countries where brucellosis is endemic, doctors must consider this diagnosis when faced with patients with systemic symptoms and diarrhea or abdominal pain. Early recognition of brucellosis and institution of appropriate therapy usually leads to a good recovery without complications.

INTRODUÇÃO: A brucelose é uma zoonose que pode envolver diferentes órgãos e tecidos. A apresentação habitual consiste em febre, cansaço, linfadenopatias, hepatoesplenomegalia, citopenias ou artrite. As manifestações gastrointestinais de brucelose humana são comuns, mas a documentação do envolvimento ileal é extremamente rara. DESCRIÇÃO DO CASO: Doente de 68 anos, sexo feminino, apresentouse com quadro com dez dias de evolução de cefaleia temporal intensa, fotofobia e sonofobia, com resposta parcial a terapêutica com paracetamol. A doente referia sudorese noturna, anorexia e dor abdominal tipo cólica após as refeições durante os últimos quatro meses seguida de diarreia. Negava náuseas, vómitos, hipersensibilidade do escalpe, visão turva, melenas ou retorragia. Negava viagens ou contacto com animais. Ao exame objetivo destacavase febre (38,3 ° C) e esplenomegalia. Os estudos laboratoriais revelaram Hb 7,8 g/dL, leucopenia (3,109 × 47/L), proteína C-reativa 5,94 mg/dL, velocidade de sedimentação 23 mm/h. A ecografia abdominal mostrou ligeiro aumento do fígado (estatose) e esplenomegalia ligeira e homogénea. Radiografia de tórax normal. Punção lombar; Doppler transcraniano, carotídeo e das artérias temporais e tomografia computorizada (CT) craniana sem alterações significativas. A CT abdominal mostrou espessamento difuso do íleon e algumas pequenas adenopatias locorregionais. As hemoculturas e serologias foram positivas para Brucela (Rosa Bengala positivo, serologia anti-Brucela ELISA IgM-positivo, IgG-negativo; reação de Huddleson positiva - título 1: 320). Foi iniciada terapêutica com rifampicina 600 mg/dia e doxiciclina 100 mg de 12 em 12 h durante 10 semanas com boa resposta clínica e laboratorial. Endoscopia digestiva alta e baixa sem alterações, apesar de a última ter sido realizada já sob terapêutica antibiótica. DISCUSSÃO: Embora as manifestações gastrointestinais de brucelose sejam comuns, pensase que a ileíte seja extremamente rara. Em países onde a brucelose é endémica, os médicos devem considerar esta hipótese diagnóstica quando na presença de sintomas sistémicos e diarreia ou dor abdominal. O reconhecimento precoce da brucelose e a instituição de terapêutica adequada levam geralmente a uma boa recuperação sem complicações.

Cannabinoid CB1 receptors in the dorsal hippocampus and prelimbic medial prefrontal cortex modulate anxiety-like behavior in rats: additional evidence.

Endocannabinoids (ECBs) such as anandamide (AEA) act by activating cannabinoid type 1 (CB1) or 2 (CB2) receptors. The anxiolytic effect of drugs that facilitate ECB effects is associated with increase in AEA levels in several encephalic areas, including the prefrontal cortex (PFC). Activation of CB1 receptors by CB1 agonists injected directly into these areas is usually anxiolytic. However, depending on the encephalic region being investigated and on the stressful experiences, opposite effects were observed, as reported in the ventral HIP. In addition, contradictory results have been reported after CB1 activation in the dorsal HIP (dHIP). Therefore, in the present paper we have attempted to verify if directly interfering with ECB metabolism/reuptake in the prelimbic (PL) portion of the medial PFC (MPFC) and dHIP would produce different effects in two conceptually distinct animal models: the elevated plus maze (EPM) and the Vogel conflict test (VCT). We observed that drugs which interfere with ECB reuptake/metabolism in both the PL and in the dentate gyrus of the dHIP induced anxiolytic-like effect, in both the EPM and in the VCT via CB1 receptors, suggesting that CB1 signaling in these brain regions modulates defensive responses to both innate and learned threatening stimuli. This data further strengthens previous results indicating modulation of hippocampal and MPFC activity via CB1 by ECBs, which could be therapeutically targeted to treat anxiety disorders.

Prospective analysis of 44 consecutive liver transplants performed at a university hospital.

PURPOSE: To analyze the intraoperative and immediate postoperative biochemical parameters of patients submitted to orthotopic liver transplantation. METHODS: Forty four consecutive orthotopic liver transplants performed from October 2009 to December 2010 were analyzed. The patients (38 male and eight female) were divided into two groups: group A, survivors, and group B, non-survivors. Fifty percent of group A patients were Chid-Pugh C, 40% Chid-Pugh B and 10% Chid-Pugh A. In group B, 52% of the patients were Chid-Pugh C, 41% Chid-Pugh B, and 17% Chid-Pugh A. All orthotopic liver transplants were performed by the piggy-back technique without a portacaval shunt in an anhepatic phase. ALT, AST, LDH and lactate levels were determined preoperatively, at five, 60 minutes after arterial revascularization of the graft and 24 and 48 hours after the end of the surgery.( or: after the surgery was finished). RESULTS: There were no preoperative clinical differences (Child and Meld) between the two groups. The times of warm and hypothermal ischemia were similar for both groups (p>0.05). Serum aminotransferases levels at five and 60 minutes after arterial revascularization of the graft were similar (p>0.05) for both groups, as also were lactate levels at the time points studied. There was no significant difference in Δ lactate between groups at any time point studied (p>0.05). No significant difference was observed between groups during the first 24 and 48 hours after surgery (p>0.05). CONCLUSION: No significant difference in any of the parameters studied was observed between groups. Under the conditions of the present study and considering the parameters evaluated, no direct relationship was detected between the intraoperative situation and the type of evolution of the patients of the two groups studied.

Prospective analysis of 44 consecutive liver transplants performed at a university hospital

PURPOSE: To analyze the intraoperative and immediate postoperative biochemical parameters of patients submitted to orthotopic liver transplantation. METHODS: Forty four consecutive orthotopic liver transplants performed from October 2009 to December 2010 were analyzed. The patients (38 male and eight female) were divided into two groups: group A, survivors, and group B, non-survivors. Fifty percent of group A patients were Chid-Pugh C, 40% Chid-Pugh B and 10% Chid-Pugh A. In group B, 52% of the patients were Chid-Pugh C, 41% Chid-Pugh B, and 17% Chid-Pugh A. All orthotopic liver transplants were performed by the piggy-back technique without a portacaval shunt in an anhepatic phase. ALT, AST, LDH and lactate levels were determined preoperatively, at five, 60 minutes after arterial revascularization of the graft and 24 and 48 hours after the end of the surgery.( or: after the surgery was finished). RESULTS: There were no preoperative clinical differences (Child and Meld) between the two groups. The times of warm and hypothermal ischemia were similar for both groups (p>0.05). Serum aminotransferases levels at five and 60 minutes after arterial revascularization of the graft were similar (p>0.05) for both groups, as also were lactate levels at the time points studied. There was no significant difference in Δ lactate between groups at any time point studied (p>0.05). No significant difference was observed between groups during the first 24 and 48 hours after surgery (p>0.05). CONCLUSION: No significant difference in any of the parameters studied was observed between groups. Under the conditions of the present study and considering the parameters evaluated, no direct relationship was detected between the intraoperative situation and the type of evolution of the patients of the two groups studied.

Liver transplantation as a multidisciplinary strategy for undergraduate education / Transplante de fígado como estratégia multidisciplinar de ensino de graduação

The program of liver transplantation can contribute in an excellent manner to undergraduate educationon a daily basis, especially in the form of scientific initiation with studies of experimental investigation in the laboratory or as formal monitoring in experimental or clinical investigation. In the latter modality, the student helps his tutoring professor in activities more related to the ward and to the Surgical Center, with studies on the clinical follow-up of patients, or with case studies in both prospective and retrospective investigations. It is the task of the adviser to attribute balanced activities whose time of execution will not interfere with formal graduation hours. Similarly, it is the responsibility of the student to structure his free time in order to devote part of it to the exercise of scientific activity. On this basis, the medical student will have the opportunity to experience the most varied facets of transplantation, acquiring the necessary systemic view of the procedure as his knowledge expands. The importance of liver transplant is exactly this, i.e., to obtain a complete idea of the whole with daily contact along time starting from the complex parts that constitute the procedure, exposes the student to diverse clinical situations rarely encountered together in other specialties, permitting him to participate in situations and discussions that are not often addressed during the medical course.

O programa de transplante de fígado presta-se, no dia a dia, de forma excelente, ao ensino de graduação, especialmente na forma de iniciação científica com trabalhos de investigação experimental em laboratórios ou na forma de monitoria formal em investigação experimental ou clínica. Nesta segunda modalidade, o aluno auxilia o professor orientador em atividades mais ligadas à enfermaria e centro cirúrgico, com trabalhos de acompanhamento clínico dos doentes, ou estudos de casos em investigações tanto prospectivas como retrospectivas. Cabe ao orientador, atribuir atividades balanceadas, cujos horários de execução não colidam com os formais da graduação. Da mesma forma, cabe ao aluno estruturar suas horas livres para dedicar parte delas ao exercício da atividade científica. Assim, o aluno de graduação, terá a oportunidade de vivenciar as mais variadas facetas do transplante, tendo dele a necessária visão sistêmica, à medida que seu conhecimento se amplia. A importância do transplante é exatamente esta, com o contato diário, ao longo do tempo, formar a ideia plena do todo a partir das complexas partes que o constituem, propiciando ao graduando participar de situações e discussões que não são frequentemente abordadas durante a graduação.