[Reversible cerebral vasoconstriction syndrome associated with anastrozole: an unusual cause of high impact]. / Sindrome de vasoconstriccion cerebral reversible asociado a anastrozol: una causa inusual de alto impacto.

INTRODUCTION: Reversible cerebral vasoconstriction syndrome (RCVS) is a low incidence disability with a multifactorial etiology and a wide array of symptoms. The main symptom is a thunderclap headache, accompanied sometimes with various neurological deficits that can lead to death. RCVS is usually diagnosed through radiological imaging technology. The treatment includes adopting general measures of monitoring, symptomatic management, identifying the etiology and acting on it to avoid recurrence. CASE REPORT: A 71-year-old woman with a history of breast cancer originally treated with tamoxifen. Due to urticaria, the anastrozole management was staggered. She was admitted for aphasia, drowsiness and a thunderclap headache. The patient reported a similar event two weeks prior admission. In brain resonance, there was evidence of small sub-arachnoidal haemorrhage (SAH) of the left parietal temporal convexity and cerebral angiography. As well as documented vasospasm in the posterior parietal region confirming the diagnosis of RCVS plus SAH. During the stay, she presented three events with the same characteristics, requiring intensive monitoring and two therapeutic panangiographies with intra-arterial nimodipine with subsequent resolution of the vessel spasm. The patient remains asymptomatic six months later. CONCLUSION: RCVS is difficult to diagnose given its wide array of symptoms and multifactorial etiology. In this case, RCVS plus SAH is associated with the use of anastrozole. So far there are no reported cases of aromatase inhibitors associated with this pathology and should be reported in the literature for pharmacovigilance.

TITLE: Sindrome de vasoconstriccion cerebral reversible asociado a anastrozol: una causa inusual de alto impacto.Introduccion. El sindrome de vasoconstriccion cerebral reversible (SVCR) es una entidad de baja incidencia, de etiologia multifactorial y amplio espectro de presentacion. El principal sintoma es la cefalea de tipo trueno. Puede estar acompañado de focalizacion neurologica y cursar con desenlaces clinicos variable que incluso pueden llevar a la muerte. El diagnostico es clinico e imaginologico, y el tratamiento incluye adoptar medidas generales de monitorizacion, manejo sintomatico, identificar la etiologia y actuar sobre ella para evitar recurrencia. Caso clinico. Mujer de 71 años con antecedente de cancer de seno, tratada inicialmente con tamoxifeno; por presentar urticaria, se escalono tratamiento con anastrozol. Ingreso por cefalea de tipo trueno, afasia anterior y somnolencia. La paciente refirio un evento similar una semana antes del ingreso. En la resonancia magnetica cerebral evidencio una hemorragia subaracnoidea (HSA) pequeña de la convexidad temporoparietal izquierda, y la panangiografia documento vasoespasmo en la region parietal posterior, lo que confirmo el diagnostico de SVCR mas HSA. Durante el ingreso presento tres eventos de iguales caracteristicas, que requirieron monitorizacion intensiva y dos panangiografias terapeuticas con nimodipino intraarterial, con posterior resolucion del vasoespasmo. Permanece asintomatica seis meses despues. Conclusion. El SVCR constituye un reto diagnostico dada su presentacion variable y su etiologia multifactorial. En este caso, el SVCR mas HSA esta asociado al uso de anastrozol. Hasta el momento no hay casos descritos de inhibidores de la aromatasa asociados a esta patologia, que debe comunicarse para su farmacovigilancia.

A comprehensive analysis of factors related to carmustine/bevacizumab response in recurrent glioblastoma.

PURPOSE: Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. METHODS/PATIENTS: In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. RESULTS: Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%). CONCLUSIONS: BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.

Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab.

BACKGROUND: The aim of this study was to compare the extent of pathologic response in patients with HER2-positive (HER2+) breast cancer treated with standard neoadjuvant chemotherapy, with or without trastuzumab (H), according to hormone receptor (HR) status. PATIENTS AND METHODS: We included 199 patients with HER2+ breast cancer from three successive cohorts of neo-adjuvant chemotherapy on the basis of paclitaxel (Taxol) (P) administered weekly (w) or three weekly (3-w), followed by 5-fluorouracil (F), doxorubicin (A) or epirubicin (E), and cyclophosphamide (C). Residual cancer burden (RCB) was determined from pathologic review of the primary tumor and lymph nodes and was classified as pathologic complete response (pCR) or minimal (RCB-I), moderate (RCB-II), or extensive (RCB-III) residual disease. RESULTS: In HR-positive (HR+) cancers, a higher rate of pathologic response (pCR/RCB-I) was observed with concurrent H + 3-wP/FEC (73%) than with 3-wP/FEC (34%, P = 0.002) or wP/FAC (47%; P = 0.02) chemotherapy alone. In HR-negative (HR-) cancers, there were no significant differences in the rate of pathologic response (pCR/RCB-I) from 3-wP/FAC (50%), wP/FAC (68%), or concurrent H + 3-wP/FEC (72%). CONCLUSIONS: Patients with HR+/HER2+ breast cancer obtained significant benefit from addition of trastuzumab to P/FEC chemotherapy; pathologic response rate was similar to that seen in HR-/HER2+ breast cancers.

Effects of neuropeptide Y, calcitonin gene-related peptide, substance P, and capsaicin on cerebral arteries in man and animals.

The smooth-muscle tone of pial, middle, and anterior cerebral arteries from humans, cats, and pigs, respectively, was studied in vitro with respect to the effects of capsaicin and various peptides which are present in local perivascular nerves. Neuropeptide Y (NPY) caused concentration-dependent, potent contractions of the cerebral vessels both in the presence and in the absence of endothelium. In contrast to the response to noradrenaline (NA) and K+, the NPY effect was not altered by changes in the extracellular Ca++ concentration. The relaxant action of the calcium antagonist nifedipine on NPY-evoked contraction of cerebral arteries was not inhibited by a Ca++-deficient medium or by a high-Ca++ medium. Calcitonin gene-related peptide (CGRP), substance P (SP), and capsaicin caused relaxation of precontracted cerebral arteries with an intact endothelium. Calcitonin gene-related peptide was the most potent dilatory agent, and removal of the endothelium did not change the CGRP response. In contrast, the ability of SP to cause relaxation was abolished after removal of the endothelium. Capsaicin, which activates sensory nerves, induced long-lasting relaxation in both the presence and absence of endothelium. In conclusion, in contrast to earlier reported data, the contractile effect of NPY seems to be largely independent of extracellular Ca++, while NA- and K+-induced contractions are dependent on extracellular Ca++. The present results suggest that the relaxant effect of nifedipine on cerebral blood vessels may involve actions other than inhibition of Ca++ influx. The relaxant effect of capsaicin is likely to be induced by release of CGRP rather than SP. The potent effects of these peptides on human pial arteries suggest that neuropeptides may be involved in the control of cerebral blood flow in man.

[Cancer of the breast in the male. Presentation of 2 cases]. / Cáncer de glándula mamaria masculina. Presentación de dos observaciones.

We present two cases of adenocarcinome of the male mammary gland, without past history of gynecomastia, cirrhosis, malnutrition, hyperoestrogenism, estron therapy for prostatic cancer, testicular tumor, Klinefelter Syndrome, parasitosis, trauma or irradiation. Male mammary adenocarcinoma is rare in all hospital. In our center we found two cases among 204 female mammary adenocarcinomas, that is one porcent, in a revisión between 1971 and 1980. Most male mammary adenocarcinomas are of the ductal/infiltrative type, early metastasis to regional ganglia or by continuity to adjacent skin.

[Reversible cerebral vasoconstriction syndrome secondary to secreting jugular paraganglioma]. / Sindrome de vasoconstriccion cerebral reversible secundario a un paraganglioma yugular secretor de metanefrinas.

TITLE: Sindrome de vasoconstriccion cerebral reversible secundario a un paraganglioma yugular secretor de metanefrinas.

Recommendations for use of marginal donors in heart transplantation: Brazilian Association of Organs Transplantation guideline.

The high prevalence of heart failure has increased the candidate list for heart transplantation; however, there is a shortage of viable donated organs, which is responsible for the high mortality of patients awaiting a transplantation. Because the marginal donor presents additional risk factors, it is not considered to be an ideal donor. The use of a marginal donor is only justified in situations when the risk of patient death due to heart disease is greater than that offered by the donor. These recommendations sought to expand the supply of donors, consequently increasing the transplant rate. We selected articles based on robust evidence to provide a substratum to develop recommendations for donors who exceed the traditional acceptance criteria. Recipient survival in the immediate postoperative period is intimately linked to allograft quality. Primary allograft failure is responsible for 38% to 40% of immediate deaths after heart transplantation: therefore; marginal donor selection must be more rigorous to not increase the surgical risk. The main donor risk factors with the respective evidence levels are: cancer in the donor (B), female donor (B), donor death due to hemorrhagic stroke (B), donor age above 50 years (relative risk [RR] = 1.5) (B), weight mismatch between donor and recipient < 0.8 (RR = 1.3) (B), ischemia > 240 minutes (RR = 1.2) (B), left ventricular dysfunction with ejection fraction below 45% (B), and use of high doses of vasoactive drugs (dopamine > 15 mg/kg·min) (B). Factors that impact recipient mortality are: age over 50 years (RR = 1.5); allograft harvest at a distance; adult recipient weighing more than 20% of the donor; high doses of vasoactive drugs (dopamine greater than 15 mg/kg·min) and ischemic time >4 hours. The use of a marginal donor is only justified when it is able to increase life expectancy compared with clinical treatment, albeit the outcomes are interior to those using an ideal donor.

[Evaluation of clinical competence in the postgraduate family medicine course, by means of the Structured Objective Clinical Test]. / Evaluación de la competencia clínica en el posgrado de medicina familiar mediante el Examen Clínico Objetivo Estructurado.

OBJECTIVE: To evaluate the clinical competence of first-year residents on the course specialising in family medicine, by applying a structured objective clinical test (SOCT) for simultaneous assessment of cognitive, affective and psychomotor areas. DESIGN: Observational and descriptive. SETTING: Family medicine clinics in the metropolitan area of Mexico City.Participants. 89 doctors on the specialist course in Family Medicine at the Autonomous University of Mexico (UNAM). MAIN MEASUREMENTS: After prior design of comparison lists, expert validation of content, and design of support material for the evaluation and pilot study, a SOCT with ten themes or sections, eight dynamic and two static, was administered. The cut-off point for competent performance was 60 out of 100, both in each section and in the overall average. The statistical analysis was univariate, using descriptive statistics. RESULTS: The overall average of scores in all sections was under 60. The highest average was 73, in the section for monitoring healthy children. In the five highest-scoring sections, the scattering was lower than in the other five. There were low scores in the family study section. CONCLUSIONS: Academic performance, as evaluated by a SOCT measuring clinical competence, was low. This kind of test enabled clinical competence to be assessed more objectively. Interval evaluation scales need to be tested so as to evaluate better the quality of the performance of clinical activities.