Apolipoprotein B and non-high-density lipoprotein cholesterol reveal a high atherogenicity in individuals with type 2 diabetes and controlled low-density lipoprotein-cholesterol.

BACKGROUND: Lipid-lowering therapy is guided by Low-density-lipoprotein cholesterol (LDL-c) levels, although the cardiovascular disease (CVD) risk could be better reflected by other lipid parameters. This study aimed at comparing a comprehensive lipid profile between patients with type 2 diabetes mellitus (T2DM) with LDL-c concentration within and above target. METHODS: A comprehensive lipid profile was characterized in 96 T2DM patients. The European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) 2016 and 2019 Guidelines for the Management of Dyslipidemias were used to define LDL-c targets. RESULTS: In this population, only 28.1 and 16.7% of patients had mean LDL-c levels within target, as defined by the 2016 and 2019 guidelines, respectively. Applying the 2016 guidelines criteria, in patients with LDL-c within target, 22, 25 and 44% presented non-high-density lipoprotein cholesterol (non-HDL-c), Apolipoprotein B (ApoB) and oxidized LDL-c levels above the recommended range, respectively, whereas according to the 2019 guidelines criteria, 50, 39 and 44% of the patients with LDL-c within target had elevated high-density lipoprotein cholesterol (HDL-c), ApoB and oxidized LDL-c levels, respectively. LDL-c was strongly correlated with non-HDL-c (r = 0.850), ApoB (r = 0.656) and oxidized LDL-c (r = 0.508). Similarly, there was a strong correlation between non-HDL-c with both ApoB (r = 0.808) and oxidized LDL-c (r = 0.588). CONCLUSIONS: These findings emphasize the limitations of only considering LDL-c concentration for cardiovascular (CV) risk assessment. Targeting only LDL-c could result in missed opportunities for CV risk reduction in T2DM patients. These data suggest that non-HDL-c, ApoB and oxidized LDL-c levels could be considered as an important part of these patients' evaluation allowing for a more accurate estimation of CV risk and hopefully better management of these high-risk patients.

Lipoprotein apheresis in the management of severe hypercholesterolemia and hyperlipoproteinemia(a)-The Portuguese experience.

BACKGROUND: Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are established causal risk factors for cardiovascular disease (CVD). Lipoprotein apheresis is often required for treatment of patients with a high risk for CVD due to hypercholesterolemia and/or hyperlipoproteinemia(a). AIM: To describe our experience with lipoprotein apheresis in patients with severe hypercholesterolemia or with hyperlipoproteinemia(a). METHODS: We retrospectively investigated patients treated with Lipoprotein apheresis using direct adsorption of lipoproteins (DALI) technique, between December 2008 and March 2018, in our center. Adverse events, acute and long term reductions in lipid parameters were analyzed. RESULTS: Between December 2008 and March 2018, a total of 950 treatments were performed in five patients, four with heterozygous familial hypercholesterolemia (HeFH), all on maximally tolerated cholesterol-lowering drug therapy and in one patient with hyperlipoproteinemia(a) and progressive CVD. In the four patients with HeFH we obtained mean acute reductions in LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) of 62.0 ± 7.8% and 60.4 ± 6.8%, respectively. Regarding long-term efficacy we achieved a mean reduction of 43.1% in LDL-C and of 41.2% in non-HDL-C. In the patient with hyperlipoproteinemia(a) we attained mean acute reductions of 60.4 ± 6.4% in Lp(a) and of 75.4 ± 7.3% in LDL-C per session and long term reductions in Lp(a) and LDL-C of 67.4% and 40.5%, respectively. Adverse events were recorded in only 1.2% of treatments. CONCLUSION: Lipoprotein apheresis is an efficient and safe treatment in severely hypercholesterolemic patients who are refractory to conservative lipid-lowering therapy or with hyperlipoproteinemia(a) and progressive CVD.

Two novel heterozygous missense variations within the GLI2 gene in two unrelated Argentine patients.

Several heterozygous GLI2 gene mutations have been reported in patients with isolated GH deficiency (IGHD) or multiple pituitary hormone deficiency (MPHD) with or without other malformations. The primary aim of this study was to analyze the presence of GLI2 gene alterations in a cohort of patients with IGHD or MPHD and ectopic/absent posterior pituitary. The coding sequence and flanking intronic regions of GLI2 gene were amplified and directly sequenced from gDNA of 18 affected subjects and relatives. In silico tools were applied to identify the functional impact of newly found variants (Polyphen2, SIFT, Mutation Taster). We identified two novel heterozygous missense variations in two unrelated patients, p.Arg231Gln and p.Arg226Leu, located in the repressor domain of the protein. Both variations affect highly conserved amino acids of the Gli2 protein and were not found in the available databases. In silico tools suggest that these variations might be disease causing. Our study suggests that the GLI2 gene may be one of the candidate genes to analyze when an association of pituitary hormone deficiency and developmental defects in posterior pituitary gland. The highly variable phenotype found suggests the presence of additional unknown factors that could contribute to the phenotype observed in these patients.

ACTH-producing adrenocortical carcinoma: an exceedingly rare diagnosis.

BACKGROUND: Adrenocortical carcinoma is a very rare endocrinopathy that has a poor prognosis and is frequently associated with ACTH-independent Cushing's syndrome. Despite having an adrenocortical carcinoma, our patient surprisingly had an ACTH-dependent Cushing's syndrome. CASE REPORT: A 26-year-old female presented with Cushing's syndrome and an abdominal mass. Imaging studies revealed an adrenal mass consistent with a high-grade malignancy. Laboratory workup showed hypercortisolism, hyperandrogenism, and hypokalemia with normal levels of metanephrines. Unexpectedly, her ACTH levels were remarkably elevated. The pathological analysis of a tumor sample was conclusive for adrenocortical carcinoma with immunopositivity for ACTH. CONCLUSIONS: Our patient suffered from an adrenocortical carcinoma that was ectopically producing ACTH. This case emphasizes that physicians should have a broad-minded approach when evaluating cases of rare endocrine malignancies.

Comparison of the accuracy of the Friedewald, Martin, and Sampson formulas to estimate very low levels of low-density lipoprotein cholesterol.

INTRODUCTION: The Martin (MF) and Sampson (SF) formulas have shown greater accuracy for low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL compared to the Friedewald formula (FF); however, some disagreement is maintained. Non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (ApoB) are alternatives to assessing cardiovascular risk in patients with very low LDL-C. The objective was to evaluate the accuracy of FF, MF, and SF formulas to estimate LDL-C < 70 mg/dL vs. directly measured LDL-C (LDLd-C) and to compare non-HDL-C and Apo-B levels between the groups of patients with concordant vs. discordant LDL-C. MATERIAL AND METHODS: This was a prospective clinical study with measurements of lipid profile and LDLd-C in 214 patients with triglycerides < 400 mg/dL. For each formula, the estimated LDL-C was compared with the LDLd-C, and the correlation, the median difference, and the discordance rate were evaluated. Non-HDL-C and Apo-B levels were compared between the groups with concordant and discordant LDL-C. RESULTS: The estimated LDL-C was < 70 mg/dL in 130 (60.7%) patients by FF, 109 (50.9%) by MF, and 113 (52.8%) by SF. The strongest correlation was found between LDLd-C and Sampson estimated LDL-C (LDLs-C) (R2 = 0.778), followed by Friedewald-estimated LDL-C (LDLf-C) (R2 = 0.680) and Martin estimated LDL-C (LDLm-C) (R2 = 0.652). Estimated LDL-C < 70 mg/dL was lower than LDLd-C, with the largest median absolute difference (25-75th) of -15 (-19 to -10) with FF. For estimated LDL-C < 70 mg/dL, the discordant rate was 43.8%, 38.1%, and 35.1%, reaching for 62.3%, 50.9%, and 50% when LDL-C < 55 mg/dL by FF, SF, and MF, respectively. Patients in the discordant group presented significantly higher levels of non-HDL-C and ApoB for all 3 formulas (p < 0.001). CONCLUSION: FF was the most inaccurate formula to estimate very low LDL-C. Despite MF and SF showing better results, their frequency in underestimating LDL-C was still considerable. In patients with falsely low estimated LDL-C, apoB and non-HDL-C were significantly higher, reflecting its true high atherogenic burden.

Treatment with TRIAC in pediatric patients with MCT8. / Tratamiento con TRIAC en pacientes pediátricos con deficiencia de MCT8.

Monocarboxylate transporters (MCTs) allow the cellular entry of thyroid hormones, especially into the central nervous system (CNS), where they are crucial for neurodevelopment. MCT8 deficiency results in the combination of hypothyroidism in the CNS and peripheral hyperthyroidism, characterized by elevated T3 levels. The only treatment currently available is 3,3',5-triiodothyroacetic acid (TRIAC), a thyroid hormone analogue aimed at improving peripheral thyrotoxicosis and preventing the progression of neurological impairment. Here we assess the clinical, imaging, biochemical, and genetic characteristics of 4 patients with MCT8 deficiency who have received TRIAC to date, the doses used, and the response to treatment.

Los transportadores de monocarboxilatos (MCT) permiten el ingreso celular de hormonas tiroideas, especialmente en el sistema nervioso central (SNC), donde son indispensables para el neurodesarrollo. La deficiencia de MCT8 produce la combinación de hipotiroidismo en SNC e hipertiroidismo periférico, caracterizada por T3 elevada. El único tratamiento actualmente disponible es el ácido 3,3',5-triyodotiroacético (TRIAC), un análogo de hormonas tiroideas que tiene como objetivo mejorar la tirotoxicosis periférica y prevenir la progresión del deterioro neurológico. En el presente artículo, se evalúan las características clínicas, imagenológicas, bioquímicas y genéticas de 4 pacientes con deficiencia de MCT8 tratados con TRIAC hasta la fecha, las dosis utilizadas y la respuesta al tratamiento.

A Rare Case of Thoracoabdominal Paraganglioma: A Case Report and Literature Review.

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors. Pheochromocytomas are derived from chromaffin cells of the adrenal medulla, while paragangliomas arise from the extra-adrenal autonomic paraganglia. Paragangliomas can derive from either parasympathetic or sympathetic paraganglia. The majority of parasympathetic ganglia-derived paragangliomas are nonfunctional and symptoms arise from mass effect, while sympathetic paragangliomas are frequently functional and present with symptoms that result from catecholamine hypersecretion. Here, we present the case of a 19-year-old female with hypertension whose biochemical tests revealed elevated plasma and urinary levels of norepinephrine and normetanephrine. Imaging studies showed a left paravertebral mass which was surgically removed. Histopathology confirmed a paraganglioma. Total surgical resection remains the gold-standard treatment and a cure can be achieved; however, all tumors may harbor malignant potential, and a long-term biochemical and imaging follow-up is required in all patients. Screening for genetic germline mutations may be helpful in identifying patients with a higher risk of recurrence or of developing other primary tumors.

[Approach to Patients with Statin Intolerance: Evidence-Based Review]. / Abordagem aos Doentes com Intolerância às Estatinas: Revisão Baseada na Evidência.

INTRODUCTION: Statins are among the most effective drugs in lowering cholesterol levels and, consequently, in reducing cardiovascular mortality and morbidity. Although generally well tolerated, they have adverse effects that may reduce patient adherence to therapy. The objective of this evidence-based review is to summarize the evidence on the effectiveness of alternative management strategies in patients with intolerance to statins. MATERIAL AND METHODS: A literature search including clinical practice guidelines, systematic reviews and meta-analyses was conducted, in January 2017, in major international databases, and considered articles published in the last 10 years. The search was complemented with research papers published over the past three years and found in the PubMed database. The level of evidence and strength of recommendation were determined using the scale Strength of Recommendation Taxonomy - SORT. RESULTS: We included eight guidelines, six systematic reviews and one research paper. DISCUSSION: The strategies proposed by the different studies vary according to the severity of symptoms of intolerance including maintenance of the statin therapy (dose reduction, addition of a statin of equal or lower intensity or alternate days' uptake) and lipid-lowering therapy with other drugs (ezetimibe monotherapy or association with statin tolerated dose). Supplementation with coenzyme Q10 or vitamin D, in order to improve adherence to treatment with statins, is not recommended. CONCLUSION: This review highlights some alternatives to address patients' intolerance to statins; however, these are mostly based on recommendations with low to moderate evidence. Therefore, further research with randomized studies involving greater number of patients is required, in order to obtain a more robust recommendation.

Introdução: As estatinas são dos fármacos mais eficazes na redução dos níveis de colesterol e, consequentemente, da morbimortalidade cardiovascular. Apesar de globalmente bem toleradas, têm efeitos secundários que podem condicionar a adesão dos doentes à terapêutica. O objetivo desta revisão é sintetizar a evidência existente acerca da eficácia das estratégias alternativas de abordagem da dislipidemia nos doentes intolerantes às estatinas.Material e Métodos: Realizámos uma pesquisa bibliográfica de normas de orientação clínica, revisões sistemáticas e meta-análises em janeiro de 2017, nas principais bases de dados internacionais, tendo sido considerados os artigos publicados nos últimos 10 anos, e ainda de artigos originais na base de dados PubMed publicados nos últimos três anos. O nível de evidência e força de recomendação foram determinados utilizando a escala de Strenght of Recommendation Taxonomy - SORT.Resultados: Incluímos oito normas de orientação clínica, seis revisões sistemáticas e um artigo original.Discussão: A abordagem ao doente intolerante às estatinas varia conforme a gravidade dos sintomas e inclui a manutenção da terapêutica com estatina (redução da dose, introdução de uma estatina de igual ou menor intensidade ou toma em dias alternados), a terapêutica com outros fármacos hipolipemiantes (ezetimiba em monoterapia ou associação com estatina em dose tolerada). A suplementação com coenzima Q10 ou com vitamina D, para melhorar a adesão ao tratamento com estatinas, está desaconselhada.Conclusão: Apesar de apontarmos algumas estratégias de abordagem à intolerância às estatinas, estas baseiam-se maioritariamente em recomendações com evidência fraca a moderada, sendo necessários estudos aleatorizados com maior número de doentes para uma recomendação mais robusta.

Novel and traditional lipid profiles in Metabolic Syndrome reveal a high atherogenicity.

Low-density-lipoprotein cholesterol (LDL-c) guides lipid-lowering therapy, although other lipid parameters could better reflect cardiovascular disease (CVD) risk. Discordance between these parameters and LDL-c has not been evaluated in metabolic syndrome (MetS) patients. We characterized a comprehensive lipid profile in 177 MetS patients. The 2016 ESC/EAS Guidelines for the Management of Dyslipidemias were used to define LDL-c targets. The atherogenic lipoprotein profile was compared in patients with LDL-c within and above the target. Only 34.4% (61) of patients had mean LDL-c levels within the guidelines and patients with LDL-c above target presented significantly elevated levels of Apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (non-HDL-c) and oxidized LDL-c. In patients with LDL-c within target, 25%, 31% and 49% presented levels above the recommended range for ApoB, non-HDL-c and oxidized LDL-c, respectively. Patients presented a strong association of LDL-c and non-HDL-c (r = 0.796), ApoB (r = 0.749) and oxidized LDL-c (r = 0.452). Similarly, non-HDL-c was strongly correlated with ApoB (r = 0.857) and oxidized-LDL-c (r = 0.555). The logistic regression model evidenced higher triglycerides and HDL-c and lower ApoB as predictors of having LDL-c within target. Reliance solely on LDL-c could result in missed opportunities for CVD risk reduction. ApoB, oxidized LDL-c, and particularly non-HDL-c, could be valuable parameters to estimate the CVD risk of MetS patients and have the potential to be targeted therapeutically.

Tratamiento con TRIAC en pacientes pediátricos con deficiencia de MCT8 / Treatment with TRIAC in pediatric patients with MCT8

Los transportadores de monocarboxilatos (MCT) permiten el ingreso celular de hormonas tiroideas, especialmente en el sistema nervioso central (SNC), donde son indispensables para el neurodesarrollo. La deficiencia de MCT8 produce la combinación de hipotiroidismo en SNC e hipertiroidismo periférico, caracterizada por T3 elevada. El único tratamiento actualmente disponible es el ácido 3,3',5-triyodotiroacético (TRIAC), un análogo de hormonas tiroideas que tiene como objetivo mejorar la tirotoxicosis periférica y prevenir la progresión del deterioro neurológico. En el presente artículo, se evalúan las características clínicas, imagenológicas, bioquímicas y genéticas de 4 pacientes con deficiencia de MCT8 tratados con TRIAC hasta la fecha, las dosis utilizadas y la respuesta al tratamiento.

Monocarboxylate transporters (MCTs) allow the cellular entry of thyroid hormones, especially into the central nervous system (CNS), where they are crucial for neurodevelopment. MCT8 deficiency results in the combination of hypothyroidism in the CNS and peripheral hyperthyroidism, characterized by elevated T3 levels. The only treatment currently available is 3,3',5-triiodothyroacetic acid (TRIAC), a thyroid hormone analogue aimed at improving peripheral thyrotoxicosis and preventing the progression of neurological impairment. Here we assess the clinical, imaging, biochemical, and genetic characteristics of 4 patients with MCT8 deficiency who have received TRIAC to date, the doses used, and the response to treatment.

Effects of myxoma virus and rabbit hemorrhagic disease virus on the physiological condition of wild European rabbits: Is blood biochemistry a useful monitoring tool?

Myxomatosis and rabbit hemorrhagic disease (RHD) are the major viral diseases that affect the wild European rabbit (Oryctolagus cuniculus). These diseases arrived in Europe within the last decades and have caused wild rabbit populations to decline dramatically. Both viruses are currently considered to be endemic in the Iberian Peninsula; periodic outbreaks that strongly impact wild populations regularly occur. Myxoma virus (MV) and rabbit hemorrhagic disease virus (RHDV) alter the physiology of infected rabbits, resulting in physical deterioration. Consequently, the persistence and viability of natural populations are affected. The main goal of our study was to determine if blood biochemistry is correlated with serostatus in wild European rabbits. We carried out seven live-trapping sessions in three wild rabbit populations over a two-year period. Blood samples were collected to measure anti-MV and anti-RHDV antibody concentrations and to measure biochemical parameters related to organ function, protein metabolism, and nutritional status. Overall, we found no significant relationships between rabbit serostatus and biochemistry. Our main result was that rabbits that were seropositive for both MV and RHDV had low gamma glutamyltransferase concentrations. Given the robustness of our analyses, the lack of significant relationships may indicate that the biochemical parameters measured are poor proxies for serostatus. Another explanation is that wild rabbits might be producing attenuated physiological responses to these viruses because the latter are now enzootic in the study area.

Checklist para el transporte intrahospitalario seguro del paciente crítico: a scoping review / Checklist para o transporte intra-hospitalar seguro do doente crítico: a scoping review / Checklist for a safe intra-hospital transport of critically ill patients: a scoping review

Transportar a un paciente crítico conlleva una serie de riesgos que pueden poner en peligro su seguridad. Conocer los riesgos asociados con el transporte intrahospitalario es esencial para mejorar su seguridad. Elegimos estudiar la lista de verificación de transporte intrahospitalario, ya que la literatura los describe como una forma práctica y simple de aumentar la seguridad. OBJETIVO: Mapear la envidencia científica existente sobre los aspectos del check list o lista de verificación garantizando la seguridad del paciente crítico en el transporte intrahospitalario. MATERIAL Y MÉTODO: Se realizó un scoping review através de la metodologia The Joanna Briggs Institute, utilizando los motores de búsqueda EBSCOhost y B-on. La investigación fue realizada en portugués, inglés y español. Fueron seleccionados artículos con texto libre, sin límite de tiempo. Los criterios incluídos: el paciente crítico adulto/anciano, transporte intrahospitalario, la lista de verificación y la seguridad del paciente. RESULTADOS: Se incluyeron 7 artículos. La mayoría de los aspectos de la lista de verificación se enfoca en la preparación del transporte, el aspecto que más se menciona es la monitorización del paciente. La parte después del transporte, aspectos de la lista de verificación solo es mencionada en 3 de los 7 artículos. CONCLUSIÓN: Todos los estudios constatan aspectos que pueden incluírse en una lista de verificación y que mejoran la seguridad de los pacientes críticos en el transporte intrahospitalario. No hay unanimidad en cuanto a qué aspectos incluir en la lista de verificación

O transporte do doente crítico acarreta um conjunto de riscos para a sua segurança. Conhecer os riscos associados ao transporte intra-hospitalar do doente crítico é essencial para melhorar a segurança do mesmo. Optou-se por abordar a checklist de transporte intra-hospitalar, uma vez que a literatura a descreve como uma forma prática e simples de aumentar a segurança. OBJETIVO: Mapear a evidência científica disponível referente aos aspetos de uma checklist que garantem a segurança do doente crítico no transporte intra-hospitalar. MATERIAL E MÉTODO: Realizou-se uma scoping review recorrendo à metodologia do The Joanna Briggs Institute, nas bases de dados utilizando os motores de busca EBSCOhost e B-on. Realizada pesquisa em Português, Inglês e Espanhol. Selecionados artigos free full text, sem limite temporal. Critérios de inclusão: o doente crítico adulto/idoso, o transporte intra-hospitalar, a checklist e a segurança do doente. RESULTADOS: Foram incluídos 7 artigos. A maioria dos aspetos da checklist que garantem a segurança do doente crítico no transporte intra-hospitalar, dizem respeito à fase da preparação do transporte, na qual o aspeto mais mencionado é a monitorização do doente. Da fase posterior ao transporte, aspetos da checklist apenas são mencionados em 3 dos 7 artigos. CONCLUSÃO: Todos os estudos abordam aspetos que são passíveis de incluir em checklist e melhoram a segurança do doente. Não existe unanimidade quanto aos aspetos a incluir na checklist do transporte intra-hospitalar

Transporting critically ill patients is has a set of risks that may jeopardize their safety. Knowing the risks associated with intrahospitalar transport of critically ill patients is essential to improving patient safety. For the sake of improving patient safety, was chosen to approach it as an intrahospitalar transport checklist, as the literature describes it as a practical and simple way to increase safety. OBJECTIVE: Map available scientific evidence regarding aspects of a checklist that ensure the safety of critically ill patients in intrahospitalar transport. MATERIAL AND METHOD: A scoping review was performed following the methodology proposed by The Joanna Briggs Institute in databases using the EBSCOhost and B-on search engines. Conducted research in Portuguese, English, and Spanish. Selected free full text articles, with no time limit. Inclusion criteria: adult/elderly critically ill patient, intrahospital transport, a checklist and patient safety. RESULTS: Included 7 articles for analysis. Most verification requests that ensure the safety of critical patients on intrahospitalar transport concern the transport preparation phase, in which patient is monitored was the most mentioned aspect. From the post-transportation phase, checklist aspects are only available in 3 of 7 articles. CONCLUSION: All studies address aspects that improve the safety of critically ill patients in intrahospitalar transport and are likely to be included in the checklist. There is no unanimity as to which aspects to include in the checklist

LDL apheresis in the treatment of familial hypercholesterolemia: experience of Hospital Santo António, Porto.

INTRODUCTION: High plasma levels of low-density lipoprotein (LDL) cholesterol are a risk factor for the development of premature atherosclerosis. Direct adsorption of lipoproteins (DALI) is an apheresis technique by which LDL cholesterol is selectively removed from whole blood. OBJECTIVE: The present study describes our experience with DALI LDL apheresis in severely hypercholesterolemic patients. METHODS: Three hypercholesterolemic patients suffering from atherosclerotic complications were treated fortnightly by DALI apheresis, in a total of 308 sessions between December 2008 and January 2013. All patients were on the highest tolerated dose of statins and other lipid-lowering drugs. RESULTS: The sessions were essentially uneventful, adverse events being recorded in only 3.6% of them. A mean 63.3% acute reduction in LDL cholesterol was obtained. CONCLUSION: DALI apheresis proved to be a simple, safe and efficient method of lipid apheresis in hypercholesterolemic patients refractory to conservative lipid-lowering therapy.

[Venous thromboembolism in patients with neurosurgical process or stroke. A prospective analysis from the RIETE registry]. / Enfermedad tromboembólica venosa en los enfermos neuroquirúrgicos y con ictus. Hallazgos del RIETE.

BACKGROUND AND OBJECTIVE: We studied the characteristics of thromboembolic disease in patients who have suffered a deep venous thrombosis or a pulmonary thromboembolism with the occurrence, two months before, of a neurosurgical process or a stroke. PATIENTS AND METHOD: We analyzed the variables of 57 patients who underwent a neurosurgical operation and those of 86 patients who suffered a stroke. These variables were included in the Computerised Records of Thromboembolic Disease. RESULTS: The average age was of 62.3 (1.9) for neurosurgical and 71.7 (1.5) for stroke patients (p < 0.001). Prophylaxis was previously applied to 31.6% of neurosurgical patients and to 37.2% of patients in the stroke group. Most patients were treated with low molecular weight heparin during the acute phase of the illness. In both groups, 50% of deaths was associated with thromboembolic disease. The proportion of deceases was related to the associated disease and it was significantly higher in the stroke group (18% versus 4.2% in the neurosurgical group, p = 0.028). CONCLUSIONS: In our study, thromboembolic disease was responsible of 50% of deaths. Stroke patients make up a group with a bad prognosis due to their older age and higher frequency of associated pathology; they have a higher risk of death.

Two novel heterozygous missense variations within the GLI2 gene in two unrelated argentine patients / Two novel heterozygous missense variations within the GLI2 gene in two unrelated Argentine patients

Several heterozygous GLI2 gene mutations have been reported in patients with isolated GH deficiency (IGHD) or multiple pituitary hormone deficiency (MPHD) with or without other malformations. The primary aim of this study was to analyze the presence of GLI2 gene alterations in a cohort of patients with IGHD or MPHD and ectopic/absent posterior pituitary. The coding sequence and flanking intronic regions of GLI2 gene were amplified and directly sequenced from gDNA of 18 affected subjects and relatives. In silico tools were applied to identify the functional impact of newly found variants (Polyphen2, SIFT, Mutation Taster). We identified two novel heterozygous missense variations in two unrelated patients, p.Arg231Gln and p.Arg226Leu, located in the repressor domain of the protein. Both variations affect highly conserved amino acids of the Gli2 protein and were not found in the available databases. In silico tools suggest that these variations might be disease causing. Our study suggests that the GLI2 gene may be one of the candidate genes to analyze when an association of pituitary hormone deficiency and developmental defects in posterior pituitary gland. The highly variable phenotype found suggests the presence of additional unknown factors that could contribute to the phenotype observed in these patients.

Mutaciones heterocigotas en el gen GLI2 fueron previamente comunicadas como causa de déficit aislado de hormona de crecimiento (IGHD) o déficit múltiple de hormonas hipofisarias (MPHD), con o sin otras malformaciones. El objetivo del estudio fue analizar la presencia de alteraciones en el gen GLI2 en un grupo de pacientes con IGHD o MPHD acompañado de neurohipófisis ectópica o ausente. La secuencia codificante y las regiones intrónicas flanqueantes del gen GLI2 fueron amplificadas y secuenciadas de manera directa a partir de ADN genómico extraído de sangre periférica proveniente de 18 sujetos afectados y sus familiares. Se utilizaron herramientas informáticas para predecir el impacto funcional de las nuevas variantes encontradas (Polyphen2, SIFT, Mutation Taster). Identificamos dos nuevas variantes heterocigotas con pérdida de sentido en dos pacientes no relacionados, p.Arg231Gln y p.Arg226Leu, localizadas en el dominio represor de la proteína. Estas variantes afectan aminoácidos altamente conservados en la secuencia proteica de GLI2 y no se encuentran informadas en las bases de datos disponibles. Las herramientas informáticas utilizadas sugieren que estas variantes pueden ser la causa del desarrollo de la enfermedad. Nuestro resultados indican que el gen GLI2 es uno de los genes candidatos a estudiar cuando existe una asociación entre déficit de hormonas hipofisarias y alteraciones en el desarrollo de la neurohipófisis. Se sugiere la existencia de otros factores adicionales que podrían contribuir a la variabilidad del fenotipo observado.

[Renin-angiotensin-aldosterone system (RAAS) and its pharmacologic modulation]. / Sistema renina-angiotensina-aldosterona e sua modulação farmacológica.

The renin-angiotensin-aldosterone system (RAAS) is a neuroendocrine complex system that regulates the modulation of salt and water homeostasis, and regulation of blood pressure. Through its multiple interactions it protects the endothelium, heart, brain and kidney. In addition, the RAAS regulates the vascular response to injury and inflammation. Chronic activation/dysregulation of the RAAS leads to hypertension and perpetuates a cascade of proinflammatory, prothrombotic and atherogenic effects associated with endorgan damage (heart, brain, kidney, endothelium). Consequently, the RAAS is an important therapeutic target in these situations. This article presents an overview of physiology, pathophysiology and pharmacologic modulation of the RAAS.

[Nephrourologic pathology in girls with Turner syndrome]. / Patología nefrourológica en niñas con síndrome de Turner.

Nephrourologic malformations in Turner syndrome are frequent, its diagnosis and follow-up is important in order to diminish the morbidity of this disease. The aim of this retrospective study was to analyze the nephrourologic pathology in 72 girls with Turner syndrome followed between 1989 and 2008 at Garrahan Hospital. The prevalence of nephrourologic involvement was 33% (24 patients). The most frequent findings were urinary system malformations, isolated (10 pacientes, 42%) or associated with renal malformations (9 patients, 37%); 5 patients (21%) had only renal malformations. Fifty percent of patients developed complications (8 urinary tract infection, 2 proteinuria and 2 arterial hypertension); however, none progressed to chronic renal failure. The prevalence of nephrourologic involvement was 33% and a half of these girls developed complications, our findings show the need of routine nephrological follow-up of girls with Turner syndrome and nephrourologic malformations.

Patología nefrourológica en niñas con síndrome de Turner / Nephrourologic pathology in girls with Turner syndrome

Las malformaciones nefrourológicas en el síndrome de Turner son frecuentes, por lo que su diagnóstico y seguimiento son importantes para disminuir la morbilidad de esta entidad. El objetivo de este trabajo retrospectivo fue analizar la patología nefrourológica en 72 niñas con síndrome de Turner atendidas entre 1989 y 2008 en el Hospital Garrahan. La prevalencia de patología nefrourológica fue del 33% (24 pacientes). Predominaron las anomalías del sistema urinario aisladas (10 pacientes, 42%) o asociadas a malformaciones renales (9 pacientes, 37%); 5 pacientes (21%) tuvieron anomalías estructurales renales aisladas. El 50% presentó complicaciones (8 infección urinaria, 2 proteinuria y 2 hipertensión arterial).

Nephrourologic malformations in Turner syndrome are frequent, its diagnosis and follow-up is important in order todiminish the morbidity of this disease. The aim of this retrospective study was to analyze the nephrourologic pathologyin 72 girls with Turner syndrome followed between 1989 and 2008 at Garrahan Hospital. The prevalence of nephrourologic involvement was 33% (24 patients). The most frequent findings were urinary system malformations, isolated (10 pacientes,42%) or associated with renal malformations (9 patients, 37%); 5 patients (21%) had only renal malformations. Fifty percent of patients developed complications (8 urinary tractinfection, 2 proteinuria and 2 arterial hypertension); however, none progressed to chronic renal failure. The prevalence of nephrourologic involvement was 33% and a half of these girls developed complications, our findings show the need of routine nephrological follow-up of girls with Turner syndrome and nephrourologic malformations.