Análisis de letalidad por COVID-19 en pacientes con demencia neurodegenerativa / Case fatality of COVID-19 in patients with neurodegenerative dementia

INTRODUCTION: The elderly population is the group most threatened by COVID-19, with the highest mortality rates. This study aims to analyse the case fatality of COVID-19 in a cohort of patients with degenerative dementia. METHODS: We conducted a descriptive case-control study of a sample of patients diagnosed with primary neurodegenerative dementia. RESULTS: Twenty-four of the 88 patients with COVID-19 included in the study died: 10/23 (43.4%) patients diagnosed with dementia and 14/65 (21.5%) controls; this difference was statistically significant. DISCUSSION: Our results suggest that case fatality of COVID-19 is significantly higher among patients with primary degenerative dementia than in other patients with similar mean ages and comorbidities

INTRODUCCIÓN: La población anciana es la más amenazada por COVID-19, con mayores tasas de mortalidad. El objetivo de este trabajo es analizar la letalidad en una cohorte de pacientes de COVID-19 con demencia degenerativa. MÉTODOS: Hicimos un estudio descriptivo de casos-control de una muestra de pacientes diagnosticados con demencias neurodegenerativas primarias. RESULTADOS: De los 88 pacientes incluidos en el estudio, 24 pacientes con COVID-19 fallecieron: 10/23 (43,4%) eran pacientes con diagnóstico de demencia y 14/65 (21,5%) pacientes del grupo control, una diferencia estadísticamente significativa. DISCUSIÓN: La letalidad entre los pacientes con demencia degenerativa primaria por COVID-19 es significativamente mayor en comparación con otros pacientes con edades medias y comorbilidades similares, según nuestro estudio

Case fatality of COVID-19 in patients with neurodegenerative dementia. / Análisis de letalidad por COVID-19 en pacientes con demencia neurodegenerativa.

INTRODUCTION: The elderly population is the group most threatened by COVID-19, with the highest mortality rates. This study aims to analyse the case fatality of COVID-19 in a cohort of patients with degenerative dementia. METHODS: We conducted a descriptive case-control study of a sample of patients diagnosed with primary neurodegenerative dementia. RESULTS: Twenty-four of the 88 patients with COVID-19 included in the study died: 10/23 (43.4%) patients diagnosed with dementia and 14/65 (21.5%) controls; this difference was statistically significant. DISCUSSION: Our results suggest that case fatality of COVID-19 is significantly higher among patients with primary degenerative dementia than in other patients with similar mean ages and comorbidities.

Embarazo y nuevo coronavirus: experiencia global reportada / Pregnancy and novel coronavirus: worldwide reported experience

INTRODUCCIÓN: La Organización Mundial de La Salud ha reportado recientemente que el nuevo foco de la pandemia global de la enfermedad Covid-19 es el continente americano. OBJETIVO: Realizar una revisión de la literatura sobre la experiencia internacional de la pandemia Covid 19 y embarazo. MÉTODO: Se realiza una búsqueda de la base de datos PubMed para las palabras clave Pregnancy / Pregnant / Novel Coronavirus / SARS-CoV-2 / Covid-19, desde el 1 de noviembre 2019 hasta el 21 de mayo 2020. RESULTADOS: Un total de 365 artículos fueron inicialmente seleccionados de acuerdo con la estrategia de búsqueda diseñada. El total de artículos revisados de acuerdo con los criterios fueron 42. Las series clínicas seleccionadas acumularon un total de 1098 embarazadas y enfermedad de Covid-19. Las co-morbilidades mas frecuentes fueron hipertensión arterial, diabetes mellitus, obesidad y asma. La mortalidad en relación con el total de pacientes fue de un 1,2 % y la transmisión al recién nacido de 1,7% (15 de 875). CONCLUSIÓN: La información obtenida permite inferir que la presentación clínica de la enfermedad es a lo menos equivalente a la de mujeres de la misma edad no embarazadas. Dada la severidad de la enfermedad por SARS-CoV-2 reportada, las lecciones aprendidas deben ser rápidamente asimiladas y utilizadas en el contexto de la situación nacional epidémica.

INTRODUCTION: The World Health Organization has recently reported that the new focus of the global pandemic of Covid-19 disease is the American continent. OBJECTIVE: To conduct a literature review on the international experience of the Covid 19 pandemic and pregnancy. METHOD: A PubMed database search is performed for the keywords Pregnancy / Pregnant / Novel Coronavirus / SARS-CoV-2 / Covid-19, from November 1, 2019 to May 21, 2020. RESULTS: A total of 365 articles were initially selected according to the designed search strategy. The total of articles reviewed according to the criteria was 42. The selected clinical series accumulated a total of 1098 pregnant women and Covid-19 disease. The most frequent comorbidities were hypertension, diabetes mellitus, obesity, and asthma. Mortality in relation to the total number of patients was 1.2% and transmission to the newborn was 1.7% (15 of 875). CONCLUSION: The information obtained allows us to infer that the clinical presentation of the disease is at least equivalent to that of non-pregnant women of the same age. Given the severity of the reported SARS-CoV-2 disease, the lessons learned must be quickly assimilated and used in the context of the national epidemic situation.

miRNA-7 and miRNA-324-5p regulate alpha9-Integrin expression and exert anti-oncogenic effects in rhabdomyosarcoma.

The prognosis of patients with metastatic rhabdomyosarcoma (RMS), the most common type of soft tissue sarcoma in children, is poor and no strategies have been identified to improve their dismal prognosis. Alpha-9 integrin (ITGA9) plays a particularly crucial role in cancer progression and invasiveness. Despite the consensus on the remarkable pro-oncogenic potential of this protein, the miRNA-mediated regulation of ITGA9 has barely been studied to date. In the present study, miR-7 and miR-324-5p were selected as the best candidates after a screening to find ITGA9 regulators, and their effects on cell proliferation and invasion in RMS are described and characterized for the first time. Interestingly, the overexpression of both miRNA produced a clear impairment of cell proliferation, while miR-7 also induced a remarkable drop in cell invasion. Furthermore, the stable overexpression of both miRNA was found to reduce tumor growth in orthotopic RMS models and miR-7 was able to impair metastatic lung colonization. Consequently, we conclude that miR-7 and miR-324-5p show anti-oncogenic and anti-metastatic potential, thereby opening up the possibility of being used as novel therapeutic tools to avoid RMS progression.

[Case fatality of COVID-19 in patients with neurodegenerative dementia]. / Análisis de letalidad por COVID-19 en pacientes con demencia neurodegenerativa.

Introduction: The elderly population is the group most threatened by COVID-19, with the highest mortality rates. This study aims to analyse the case fatality of COVID-19 in a cohort of patients with degenerative dementia. Methods: We conducted a descriptive case-control study of a sample of patients diagnosed with primary neurodegenerative dementia. Results: Twenty-four of the 88 patients with COVID-19 included in the study died: 10/23 (43.4%) patients diagnosed with dementia and 14/65 (21.5%) controls; this difference was statistically significant. Discussion: Our results suggest that case fatality of COVID-19 is significantly higher among patients with primary degenerative dementia than in other patients with similar mean ages and comorbidities.

Preoperative planning of lymphaticovenous anastomosis: The use of magnetic resonance lymphangiography as a complement to indocyanine green lymphography.

BACKGROUND: Lymphaticovenous anastomosis (LVA) is a surgical treatment for lymphedema that requires identification and mapping of functional lymphatic channels. This technique was performed blindly for years because of the lack of suitable methods of study. Progress in imaging techniques and the introduction of Indocyanine green lymphography (ICG-L) represented a significant advancement in lymphedema management. Magnetic resonance lymphangiography (MRL) has also helped improve knowledge about lymphedema anatomy and pathophysiology. We now present our protocol based on both ICG-L and MRL for optimal LVA preoperative planning. METHODS: A prospective study between April 2010 and June 2015 was conducted in 82 patients (77 females, mean age 45.5 years) with stage I (9.8%), II (73.2%), and III (17.0%) lymphedema. All patients underwent lymphedema surgical treatment with LVA. Surgery was planned based on preoperative information from ICG- L and MRL. RESULTS: We obtained a mean of 6.87 lymphatic locations per extremity from MRL and selected a mean of 4.04 for LVA. When MRL data coincided with ICG-L data, we found a functional lymphatic vessel in 96.9% of cases and performed LVA successfully in 91.4%. CONCLUSIONS: ICG-L and MRL are noninvasive techniques that provide images of the lymphatic system with sufficient temporal and spatial resolution to depict functional lymphatic vessels. Such knowledge is essential for preoperative planning of LVA microsurgery. We present our protocol for the approach of surgical treatment of lymphedema. This protocol represents a step forward in unifying patient selection criteria and achieving safe, effective, and rational surgery.

Dynamic changes of depolarizing GABA in a computational model of epileptogenic brain: Insight for Dravet syndrome.

Abnormal reemergence of depolarizing GABAA current during postnatal brain maturation may play a major role in paediatric epilepsies, Dravet syndrome (DS) being among the most severe. To study the impact of depolarizing GABA onto distinct patterns of EEG activity, we extended a neural mass model as follows: one sub-population of pyramidal cells was added as well as two sub-populations of interacting interneurons, perisomatic-projecting interneurons (basket-like) with fast synaptic kinetics GABAA (fast, I1) and dendritic-projecting interneurons with slow synaptic kinetics GABAA (slow, I2). Basket-like cells were interconnected to reproduce mutual inhibition mechanisms (I1➔I1). The firing rate of interneurons was adapted to mimic the genetic alteration of voltage gated sodium channels found in DS patients, SCN1A(+/-). We implemented the "dynamic depolarizing GABAA" mediated post-synaptic potential in the model, as some studies reported that the chloride reversal potential can switch from negative to more positive value depending on interneuron activity. The "shunting inhibition" promoted by GABAA receptor activation was also implemented. We found that increasing the proportion of depolarizing GABAA mediated IPSP (I1➔I1 and I1➔P) only (i.e., other parameters left unchanged) was sufficient to sequentially switch the EEG activity from background to (1) interictal isolated polymorphic epileptic spikes, (2) fast onset activity, (3) seizure like activity and (4) seizure termination. The interictal and ictal EEG patterns observed in 4 DS patients were reproduced by the model via tuning the amount of depolarizing GABAA postsynaptic potential. Finally, we implemented the modes of action of benzodiazepines and stiripentol, two drugs recommended in DS. Both drugs blocked seizure-like activity, partially and dose-dependently when applied separately, completely and with a synergic effect when combined, as has been observed in DS patients. This computational modeling study constitutes an innovative approach to better define the role of depolarizing GABA in infantile onset epilepsy and opens the way for new therapeutic hypotheses, especially in Dravet syndrome.

Oncological safety of breast cancer patients undergoing free-flap reconstruction and lipofilling.

BACKGROUND: Autologous fat grafting is a widely accepted approach for breast reconstruction after mastectomy but its oncological safety has not been established. This study aimed to compare recurrence in patients who underwent fat-grafting procedures after autologous breast reconstruction and those who did not. PATIENTS AND METHODS: We retrospectively reviewed 207 consecutive patients, who underwent mastectomy and reconstruction using free flap surgery. We divide them in two groups: a study group of patients who underwent fat grafting procedure and a control group of patients who did not. Outcome regarding local and regional recurrence was compared between the two groups. Particularly, we studied recurrences from primary surgery to baseline (first lipofilling) and from baseline to most recent follow-up. RESULTS: Median follow-up was 60 months from surgery to baseline and 29 months from baseline to most recent follow-up. The overall observational period after mastectomy in the control group was 120 months. Local recurrence was observed in 6 patients from the study group, respectively 3 in the first observational period and 3 after the fat grafting procedure. The control group, as the study one, presented a total of 6 recurrences (p = 0.555; Hazard Ratio free flap and lipo vs only free flap: = 0.66; 95% CI 0.16-2.66). CONCLUSIONS: We found no significant differences in recurrence between patients who underwent fat grafting and those who did not. These encouraging findings support previous results but larger series of patients are required to confirm long-term oncological safety in these procedures.

Management of hypotension in preterm infants (The HIP Trial): a randomised controlled trial of hypotension management in extremely low gestational age newborns.

BACKGROUND: Extremely preterm babies (delivered at <28 completed weeks of gestation) are frequently diagnosed with hypotension and treated with inotropic and pressor drugs in the immediate postnatal period. Dopamine is the most commonly used first-line drug. Babies who are treated for hypotension more frequently sustain brain injury, have long-term disability or die compared to those who are not. Despite the widespread use of drugs to treat hypotension in such infants, evidence for efficacy is lacking, and the effect of these agents on long-term outcomes is unknown. HYPOTHESIS: In extremely preterm babies, restricting the use of dopamine when mean blood pressure (BP) values fall below a nominal threshold and using clinical criteria to determine escalation of support ('restricted' approach) will result in improved neonatal and longer-term developmental outcomes. RESEARCH PLAN: In an international multi-centre randomised trial, 830 infants born at <28 weeks of gestation, and within 72 h of birth, will be allocated to 1 of 2 alternative treatment options (dopamine vs. restricted approach) to determine the better strategy for the management of BP, using a conventional threshold to commence treatment. The first co-primary outcome of survival without brain injury will be determined at 36 weeks' postmenstrual age and the second co-primary outcome (survival without neurodevelopmental disability) will be assessed at 2 years of age, corrected for prematurity. DISCUSSION: It is essential that appropriately designed trials be performed to define the most appropriate management strategies for managing low BP in extremely preterm babies.

Barcelona consensus on supermicrosurgery.

The popularity of supermicrosurgery has increased dramatically over the past few years, but the lack of agreement regarding the name of the technique and its applications has caused misunderstandings among microsurgeons when trying to communicate and compare surgical procedures. We report the consensus reached on the name used to refer to supermicrosurgery techniques following the First European Conference on Supramicrosurgery held in Barcelona (Spain) on March 4-5, 2010. Present applications, advantages, and disadvantages of supermicrosurgery are discussed. It was agreed that supermicrosurgery was the most accurate name to reflect the essence of this extremely delicate technique. According to Koshima, supermicrosurgery is a technique of microneurovascular anastomosis for vessels of 0.3 to 0.8 mm and single nerve fascicles. The range of applications for this technique has increased rapidly and now includes lymphedema treatment, nerve reconstruction, replantation and reconstruction of amputated fingertips, microsurgical flap salvage, and new possibilities for free tissue transfer. Supermicrosurgery is a remarkably useful reconstructive tool that involves a great deal of skill and has a steep learning curve for the microsurgeon to master. Although it is currently performed by only a minority of microsurgeons, we consider it will be incorporated into conventional microsurgery in the near future.

Modeling and simulation as a tool to bridge efficacy and safety data in special populations.

The registration and approval of novel medicines have traditionally been based on evidence arising from large prospective trials. Such an approach is often not possible or unsuitable to evaluate the benefit-risk balance in special populations (e.g., children, ethnic groups, rare diseases). Inferences by modeling and simulation can play a major role in evidence synthesis. A framework is proposed that promotes its acceptability and the basis for decision making during development, registration, and therapeutic use of drugs.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e28; doi:10.1038/psp.2013.6; advance online publication 27 February 2013.

A prospective open-labeled trial with levetiracetam in pediatric epilepsy syndromes: continuous spikes and waves during sleep is definitely a target.

Although LVT is currently extensively prescribed in childhood epilepsy, its effect on the panel of refractory epilepsy syndromes has not been entirely evaluated prospectively. In order to study the efficacy and safety of LVT as adjunctive therapy according to syndromes, we included 102 patients with refractory seizures (6 months to 15 years) in a prospective open-labeled trial. The responder rate was respectively 36% and 32% at 3 and 6 months with 6% and 7% patients becoming seizure free. Among the responders at 6 months (n=33), seizure frequency decreased by 66% and 79% at 3 and 6 months LVT compared to baseline. The highest benefit was for CSWS patients with 2/3 responders, 50% seizure free and no aggravation. LVT provided respectively 39% and 42% responders in focal and absence epilepsies. Infantile spasms and Dravet syndrome experienced the lowest efficacy. No patient with myoclonic-astatic epilepsy or Lennox-Gastaut syndrome was aggravated. LVT dose over 40 mg/kg/d was associated with a lower response rate. Tolerability was excellent. In spite of a small sample, we assume that CSWS is a good candidate for a randomized-controlled trial with LVT.

Rol de las trombofilias en infertilidad: ¿juegan un rol? / The role of thrombophilias in infertility: do they have a role?

Las trombofilias son un grupo de enfermedades que favorecen la formación de trombosis, tanto arteriales como venosas, y han sido asociadas con diferentes complicaciones durante el embarazo, entre las cuales podemos mencionar: aborto recurrente, preclampsia, restricción de crecimiento intrauterino y muerte fetal in útero, entre otras. Recientemente, se ha sugerido una asociación entre trombofilias e infertilidad. Las mutaciones de la enzima Metilentetrahidrofolato Reductasa (MTHFR) y de Leiden se encuentran con mayor frecuencia en pacientes con infertilidad de causa desconocida, al compararlas con grupos controles. Durante la etapa de estimulación ovárica diversas trombofilias han sido vinculadas con la aparición de sindrome de hiperestimulación ovárica severo. Por último, las pacientes con historia de falla recurrente de implantación, luego de múltiples ciclos de fertilización in Vitro, demuestran una mayor prevalencia de trombofilias que las pacientes con éxito en dichas terapias. Este artículo presenta una revisión de las publicaciones relevantes que abordaran los distintos aspectos de la relación entre trombofilias e infertilidad hasta agosto de 2009. El objetivo es describir los estudios utilizados y sus implicancias en el manejo de la pareja infértil.

Thrombophilias are a group of conditions that favor the genesis of arterial/venous thrombosis. Several complications throughout pregnancy have been associated with trhombophilias, including recurrent spontaneous abortion, preeclampsia, intrauterine growth restriction and fetal demise. Recently, an asociation has been sugested between infertility and thrombophilias, involving diferent aspects of the infertile couple therapy. MTHFR and Leiden mutations can be found more frecuently in patients with diagnosis of unknown infertility when compared with control groups. During ovarian estimulation, thrombophilias have been linked with severe ovarian hiperstimulation syndrome. Furthermore, patients with recurrent implantation failure after in vitro fertilization therapy show a higher rate of thrombophilias than patients with succesful IVF therapy. A review of the relevant publications concerning the topic thrombophilia and infertility until august 2009 is presented in this article. The aim of this article is to describe the results of the studies and its relevance in the infertile couple treatment.

Histerectomía posparto: experiencia de Clínica Las Condes / Postpartum hysterectomy: Clínica Las Condes experience

Objetivo: Analizar la experiencia clínica de pacientes sometidas a histerectomía posparto (HPP). Método: Estudio retrospectivo de la HPP efectuadas en Clínica Las Condes entre enero de 2000 y diciembre de 2009. Resultados: Hubo 15.356 partos con 34 casos de HPP (incidencia de 2,2 histerectomías/1000 partos). La edad materna promedio fue de 36 años; 97 por ciento eran multíparas. La edad gestacional promedio al parto fue 36,1 semanas (rango: 27-40). Causas principales: acretismo placentario (61,8 por ciento), inercia uterina (20,6 por ciento) y rotura uterina (8,8 por ciento). En el 29,4 por ciento se realizó además la ligadura de arterias hipogástricas. Histerectomía total en el 85,3 por ciento. El 91,2 por ciento presentó complicaciones, la más frecuente correspondió a lesión vesical asociada a acretismo placentario (26,5 por ciento). En el postoperatorio inmediato hubo 29 casos de anemia, 10 casos de coagulación intravascular diseminada, 2 casos de hemoperitoneo (reoperadas) y 2 pacientes con choque hipovolémico. Hubo 1 caso de trombosis pelviana, 1 caso de trombosis de vena ovárica y 1 caso de fasceitis necrotizante. Tardíamente hubo 3 casos de depresión, 1 tromboembolismo pulmonar, 1 fístula vésico-vaginal y 1 proceso inflamatorio pelviano. No hubo muertes maternas. Transfusión de sangre y/o hemoderivados en 76,5 por ciento. Hubo 1 mortinato y 2 mortineonatos con un 8,5 por ciento (3/35) de muerte perinatal. Conclusiones: La HPP es una intervención de urgencia que se plantea frente a una hemorragia severa, secundaria a diversas patologías, durante o posterior al parto, asociada frecuentemente con cesárea anterior e inercia uterina.

Objetive: To analyze the clinical experience of peripartum hysterectomy (PH). Method: Retrospective review of women who required PH at Las Condes Clinic since January 2000 to December 2009. Results: In the study period 15,356 patients were delivered with 34 cases of PH (incidence: 2.2/1000 deliveries). The mean age was 36 years old, 97 percent were multiparous. The mean gestational age at delivery was 36.1 weeks (range: 27-40). Causes: placenta accreta (61.8 percent), uterine atony (20.6 percent) and uterine rupture (8.8 percent). In 29.4 percent a bilateral hypogastric ligation was added to the hysterectomy. Total hysterectomy was performed in 85.3 percent of cases. There was at least one complication in 91.2 percent women. The intraopertive bladder injury associated with placenta accreta was the most frequent complication (26.5 percent). Postoperative complications: 29 cases of anemia, 10 cases of disseminated intravascular coagulopathy, 2 hemoperitoneum that required surgical reexploration, 2 cases of hypovolemic shock, 1 case of pelvic thrombosis, 1 case of ovarian vein thrombosis and 1 case of necrotizing fasceitis. Late complications included depression, pulmonary embolism, bladder-vagina fistula and pelvic inflammatory disease. 76.5 percent required transfusion. There were no cases of maternal death with 8.5 percent of perinatal death. Conclusions: PH it is performed in patients with severe bleeding during or after labor and delivery, frequently is associated with serious maternal morbidity. Previous cesarean section with abnormal placental implantation and uterine atony were the most frequent indications.

Pre-clinical and clinical evaluation of nuclear tracers for the molecular imaging of vulnerable atherosclerosis: an overview.

Cardiovascular diseases (CVD) are the leading cause of mortality worldwide. Despite major advances in the treatment of CVD, a high proportion of CVD victims die suddenly while being apparently healthy, the great majority of these accidents being due to the rupture or erosion of a vulnerable coronary atherosclerotic plaque. A non-invasive imaging methodology allowing the early detection of vulnerable atherosclerotic plaques in selected individuals prior to the occurrence of any symptom would therefore be of great public health benefit. Nuclear imaging could allow the identification of vulnerable patients by non-invasive in vivo scintigraphic imaging following administration of a radiolabeled tracer. The purpose of this review is to provide an overview of radiotracers that have been recently evaluated for the detection of vulnerable plaques together with the biological rationale that initiated their development. Radiotracers targeted at the inflammatory process seem particularly relevant and promising. Recently, macrophage targeting allowed the experimental in vivo detection of atherosclerosis using either SPECT or PET. A few tracers have also been evaluated clinically. Targeting of apoptosis and macrophage metabolism both allowed the imaging of vulnerable plaques in carotid vessels of patients. However, nuclear imaging of vulnerable plaques at the level of coronary arteries remains challenging, mostly because of their small size and their vicinity with unbound circulating tracer. The experimental and pilot clinical studies reviewed in the present paper represent a fundamental step prior to the evaluation of the efficacy of any selected tracer for the early, non-invasive detection of vulnerable patients.

Relationship between GSTP1 Ile(105)Val polymorphism and docetaxel-induced peripheral neuropathy: clinical evidence of a role of oxidative stress in taxane toxicity.

BACKGROUND: Glutathione-S-transferases (GST) regulate the cellular response to oxidative stress. We previously highlighted the importance of oxidative stress in taxane toxicity and therefore investigated the relationship between the GST isoforms M1, T1 and P1 gene polymorphisms and docetaxel (Taxotere)-induced peripheral neuropathy (DIPN). PATIENTS AND METHODS: The GSTM1 (null), GSTT1 (null) and GSTP1 (Ile(105)Val and Ala(114)Val) polymorphisms were determined in a cohort of cancer patients treated with docetaxel and entered in a clinical trial database. The relationship between GST polymorphisms and grade > or = 2 DIPN as primary end point was studied. RESULTS: Fifty-eight patients (median age 61 years) received a total of 261 cycles of docetaxel given as single agent. Patients with GSTP1 (105)Ile/(105)Ile genotype had a higher risk of developing a grade > or = 2 DIPN than did those with other GSTP1 genotypes (8 of 27 versus 2 of 31, respectively, odds ratio 6.11; 95% confidence interval 1.17-31.94; P = 0.03). In multivariate analysis, grade > or = 2 DIPN was strongly correlated with GSTP1 (105)Ile/(105)Ile genotype (P = 0.01) and the number of cycles (P = 0.03). CONCLUSION: We found a significant correlation between GSTP1 (105)Ile/(105)Ile genotype and the development of grade > or = 2 DIPN. This finding strongly suggests a role of oxidative stress in the pathophysiology of DIPN.

[Drug resistance in partial epilepsy: epidemiology, mechanisms, pharmacogenetics and therapeutical aspects]. / La pharmacorésistance des épilepsies partielles : épidémiologie, mécanismes, pharmacogénétique, perspectives thérapeutiques.

It has been established that 20-30% of epilepsies are not controlled by antiepileptic drugs. Drug resistance is associated with several major problems, including prognosis, cognitive function, behavior, mortality, cost and quality of life. Apart from classic risk factors for drug resistance, such as neurological, psychiatric, imaging, EEG abnormalities, a high frequency of seizures before medical therapy and complex febrile convulsions, the potential role of multidrug transporters as well as their genetic control and the altered sensitivity of neuronal drug receptors has gained growing attention. In the future, pharmaceutical engineering may bypass these factors. To a certain extent, drug resistance may develop progressively in a neurobiological process and the control of this process could limit its development.

Emerging therapeutic options for breast cancer chemotherapy during pregnancy.

BACKGROUND: Breast cancer is the commonest solid tumor observed during pregnancy. Anthracycline-based chemotherapy is feasible during the 2nd and 3rd trimesters of pregnancy, but few data are available on recent and highly active drugs taxanes, vinorelbine and anti-HER-2 agents in this setting. PATIENTS AND METHODS: We carried out a comprehensive review of reports documenting the use of taxanes, vinorelbine, trastuzumab and lapatinib during pregnancy in the English literature, in order to evaluate their safety profile in pregnant patients. RESULTS: Twenty-four pregnancies are described, in which no grade 3-4 maternal toxicity nor malformation in the offspring was reported. Whereas only one report studied the pharmacokinetics of paclitaxel (Taxol) during pregnancy, several preclinical reports indicate that the placental P-glycoprotein could prevent the transplacental transfer of taxanes and vinorelbine. The use of trastuzumab was associated with the occurrence of anhydramnios in three of six cases. CONCLUSION: The administration of recent drugs taxanes and vinorelbine seems feasible during the 2nd and 3rd trimesters of pregnancy, with a favorable toxicity profile. In contrast, anti-HER-2 agents may obscure the normal development of the fetal kidney, and should be avoided during pregnancy.

[Transthoracic echocardiography in stroke performed by neurologist: pilot study]. / Ecocardiografía transtorácica realizada por neurólogos en patología vascular: estudio piloto.

INTRODUCTION: The aim of this study is to assess concordance between transthoracic echocardiography (TTE) performed by neurologists and cardiologists for the screening of cardioembolic sources in patients with ischemic stroke. METHODS: We examined prospectively 27 consecutive patients with ischemic stroke. A potential source of embolism in all of the patients was sought by means of a TTE study. This study was performed by one neurologist after one-month full-time training on the technique and independently by one cardiologist whose results were considered as the reference standard. Regarding the risk of cardioembolism, findings from TTE studies were considered as normal, or indicative of either moderate or high risk, according to the TOAST criteria. Agreement between the two observers on the diagnosis of cardioembolic source was analyzed with the Cohen's Kappa Test (K). A K > 0,6 was considered as good agreement. RESULTS: The 27 patients studied had a mean age of 68,7 +/- 10,2 years and 70 % were men. A cardioembolic source was detected in 9 patients by the cardiologist and 8 of these were also identified by the neurologist: in 1 patient a mitral annulus calcification was not detected in the examination performed by the neurologist. In 2 patients with poor echocardiographic window, the neurologist underestimated the left ventricular function. Diagnostic agreement between both examinations was 88,9 % (K: 0,77; p = 0,001). CONCLUSION: Compared with cardiologists, trained neurologists show a fairly high degree of accuracy in the TTE screening of patients with stroke. Those cases with poor echocardiographic window or with abnormal findings should be confirmed by the cardiologists.