Venetoclax-resistant CLL cells show a highly activated and proliferative phenotype.

Venetoclax treatment has demonstrated efficacy and a safety profile in chronic lymphocytic leukemia (CLL) patients, however the emergence of resistant cells is a current complication. We and others, previously reported that the activation of CLL cells by signals that mimic microenvironment stimuli favors the upregulation of anti-apoptotic proteins from B cell lymphoma-2 (BCL-2) family that are not targeted by venetoclax, reducing malignant cell sensitivity to the drug. We here studied venetoclax-resistant CLL cells generated in vitro by autologous activated T lymphocytes, and found that they showed an aggressive phenotype characterized by increased expression of activation and proliferation markers. Moreover, surviving cells expressed high levels of B cell lymphoma-extra-large (BCL-XL) and/or myeloid cell leukemia-1 (MCL-1), and a sustained resistance to a second treatment with the drug. Interestingly, the spleen tyrosine kinase (SYK) inhibitor entospletinib, and the phosphoinositide 3-kinase delta (PI3Kδ) inhibitor idelalisib, reduced T cell activation, impaired the generation of leukemic cells with this aggressive phenotype, and were able to restore CLL sensitivity to venetoclax. Our data highlight a novel combination to overcome resistance to venetoclax in CLL.

Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia.

Hypogammaglobulinemia is the most frequently observed immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of all isotypes (IgG, IgM and IgA), standard immunoglobulin (Ig) preparations for replacement therapy administrated to these patients contain more than 95% of IgG. Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM and IgA (IVIgGMA), with the potential benefit to restore the Ig levels of all isotypes. Because IVIg preparations at high doses have well-documented anti-inflammatory and immunomodulatory effects, we aimed to evaluate the capacity of Pentaglobin and a standard IVIg preparation to affect leukemic and T cells from CLL patients. In contrast to standard IVIg, we found that IVIgGMA did not modify T cell activation and had a lower inhibitory effect on T cell proliferation. Regarding the activation of leukemic B cells through BCR, it was similarly reduced by both IVIgGMA and IVIgG. None of these IVIg preparations modified spontaneous apoptosis of T or leukemic B cells. However, the addition of IVIgGMA on in vitro cultures decreased the apoptosis of T cells induced by the BCL-2 inhibitor, venetoclax. Importantly, IVIgGMA did not impair venetoclax-induced apoptosis of leukemic B cells. Overall, our results add new data on the effects of different preparations of IVIg in CLL, and show that the IgM/IgA enriched preparation not only affects relevant mechanisms involved in CLL pathogenesis but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation.

Underutilization of insulin and better metabolic control. A NOVA clinic experience.

OBJECTIVE: To present the results of metabolic control in patients with type 2 Diabetes Mellitus from a private clinic in Northern Mexico. METHODS: This cross-sectional study used retrospective data obtained from electronic records from a private outpatient clinic at the end of 2018. Inclusion criteria were a diagnosis of T2DM and age ≥ 18 years. Baseline characteristics (age, gender, drug use) were reported. The achievement of glycated hemoglobin goals was established as <7%. RESULTS: A total of 3820 patients were evaluated. Their mean age was 59.86 years (+/-15.01). Of the population, 46.72% were men, and 53.28% were women. Glycated hemoglobin goals were adequate in 1872 (54%) patients. There were 3247 patients (85%) treated with oral medications, of which 1948 (60%) reported glycated hemoglobin less than 7%. Insulin use was reported in 573 (15%) patients, with 115 (20%) reporting glycated hemoglobin less than 7%. The most frequently used basal insulin was glargine in 401 (70%) patients. CONCLUSIONS: Our findings are clearly higher than the control rate reported by our national health surveys of 25% with glycated hemoglobin < 7%, but similar to that reported in other countries. The most commonly used therapeutic scheme was the combination of oral hypoglycemic agents. The percentage of cases that include insulin in their treatment was lower. Clinical inertia to insulin initiation and intensification has been defined as an important cause of this problem.

CIRSE Standards of Practice on Analgesia and Sedation for Interventional Radiology in Adults.

This CIRSE Standards of Practice document provides best practices for the safe administration of procedural sedation and analgesia for interventional radiology procedures in adults. The document is aimed at health professionals involved in the provision of sedation and analgesia during interventional radiology procedures. The document has been developed by a writing group consisting of physicians with internationally recognised expertise in interventional radiology, and analgesia and sedation.

COVID-19 Outbreak: Infection Control and Management Protocol for Vascular and Interventional Radiology Departments-Consensus Document.

COVID-19 (SARS-CoV-2 virus) pandemic was recently declared by the WHO as a global health emergency. A group of interventional radiology senior experts developed a consensus document for infection control and management of patients with COVID-19 in interventional radiology (IR) departments. This consensus statement has been brought together at short notice with the help of different protocols developed by governmental entities and scientific societies to be adapted to the current reality and needs of IR Departments. Recommendations are the specific strategies to follow in IR departments, preventive measures and regulations, step by step for donning and doffing personal protective equipment, specific IR procedures which can not be delayed, and aerosol-generating procedures in IR with COVID-19 patients. It is advisable with this document to be adapted to local workplace policies.

Underutilization of insulin and better metabolic control. A NOVA clinic experience

SUMMARY OBJECTIVE To present the results of metabolic control in patients with type 2 Diabetes Mellitus from a private clinic in Northern Mexico, METHODS This cross-sectional study used retrospective data obtained from electronic records from a private outpatient clinic at the end of 2018. Inclusion criteria were a diagnosis of T2DM and age ≥ 18 years. Baseline characteristics (age, gender, drug use) were reported. The achievement of glycated hemoglobin goals was established as <7%. RESULTS A total of 3820 patients were evaluated. Their mean age was 59.86 years (+/-15.01). Of the population, 46.72% were men, and 53.28% were women. Glycated hemoglobin goals were adequate in 1872 (54%) patients. There were 3247 patients (85%) treated with oral medications, of which 1948 (60%) reported glycated hemoglobin less than 7%. Insulin use was reported in 573 (15%) patients, with 115 (20%) reporting glycated hemoglobin less than 7%. The most frequently used basal insulin was glargine in 401 (70%) patients. CONCLUSIONS Our findings are clearly higher than the control rate reported by our national health surveys of 25% with glycated hemoglobin < 7%, but similar to that reported in other countries. The most commonly used therapeutic scheme was the combination of oral hypoglycemic agents. The percentage of cases that include insulin in their treatment was lower. Clinical inertia to insulin initiation and intensification has been defined as an important cause of this problem.

RESUMO OBJETIVO Apresentar os resultados do controle metabólico de pacientes com Diabetes Mellitus tipo 2 em uma clínica privada no norte do México, MÉTODOS Este estudo transversal utilizou dados retrospectivos obtidos em prontuários eletrônicos de um ambulatório privado no final de 2018. Os critérios de inclusão foram o diagnóstico de DM2 e idade ≥ 18 anos. Características basais (idade, sexo, uso de drogas) foram relatadas. A realização de metas de hemoglobina glicada foi estabelecida como <7%. RESULTADOS Um total de 3820 pacientes foram avaliados. A média de idade foi de 59,86 anos (+/- 15,01). Da população, 46,72% eram homens e 53,28% eram mulheres. Objetivos de hemoglobina glicada foram adequados em 1872 (54%) pacientes. Havia 3247 pacientes (85%) tratados com medicamentos orais relatando em 1948 (60%) menos de 7%. O uso de insulina foi relatado em 573 (15%) pacientes, com 115 (20%) relatando menos de 7%. A insulina basal mais utilizada foi a glargina, em 401 (70%) pacientes. CONCLUSÕES Nossos resultados são claramente mais altos do que a taxa de controle relatada por nossos levantamentos nacionais de saúde de 25% com hemoglobina glicada <7%, mas semelhante à relatada em outros países. O esquema terapêutico mais utilizado foi a combinação de hipoglicemiantes orais. A porcentagem de casos que incluem insulina no tratamento foi menor. A inércia clínica à iniciação e intensificação da insulina tem sido definida como uma importante causa desse problema.

Immunoregulatory effects of Lurbinectedin in chronic lymphocytic leukemia.

Despite significant therapeutic improvements chronic lymphocytic leukemia (CLL) remains an incurable disease and there is a persistent pursuit of new treatment alternatives. Lurbinectedin, a selective inhibitor of active transcription of protein-coding genes, is currently in phase II/III clinical trials for solid tumors such as small-cell lung cancer (SCLC). In this study, we aimed to evaluate the activity of Lurbinectedin on circulating mononuclear cells from CLL patients and to determine whether Lurbinectedin could affect the cross-talk between B-CLL cells and the tumor microenvironment. We found that Lurbinectedin induced a dose- and time-dependent death in all cell types evaluated, with B cells, monocytes and monocytic myeloid derived suppressor cells (Mo-MDSC) being the most susceptible populations. At sub-apoptotic doses, Lurbinectedin decreased the expression of CCR7 in B-CLL cells and impaired their migration towards CCL19 and CCL21. Furthermore, low concentrations of Lurbinectedin stimulated the synthesis of pro-IL1ß in monocytes and nurse-like cells, without inducing the inflammasome activation. Altogether, these results indicate that Lurbinectedin might have antitumor activity in CLL due to its direct action on leukemic cells in combination with its effects on the tumor microenvironment. Our findings encourage further investigation of Lurbinectedin as a potential therapy for CLL.

Development of a dispersive liquid-liquid microextraction coupled with magnetic dispersive microsolid phase extraction for determination of triazines in wastewater samples.

The combination of two microextraction techniques (dispersive liquid-liquid microextraction [DLLME] and magnetic dispersive microsolid phase extraction [MDMSPE]) was developed and reported for atrazine and simazine preconcentration from wastewater samples. The proposal methodology involved the use of magnetite supports functionalized with different alkyl or phenyl groups. The magnetic adsorbents were synthesized by the solvothermal method assisted by microwave, characterized, and used in the sample preconcentration of atrazine and simazine. The method validation included parameters such as the wastewater matrix effect, repeatability, and recovery. The analyte separation and quantification were performed by high-performance liquid chromatography with ultraviolet detection (HPLC-DAD). Parameters, such as the polarity and mass of magnetic solids and pH, were evaluated to provide better extraction performance. The highest recoveries (> 95%) were obtained with 50 mg of the phenyl group support (CS2) at pH 5, using 5 mL of the sample and carbon tetrachloride and methanol, as extraction and dispersive solvents, respectively. The lowest limits of detection (LOD) achieved were 13.16 and 13.86 ng L-1, and the limits of quantification (LOQ) were 43.89 and 46.19 ng L-1 for simazine and atrazine, respectively, with repeatability (expressed as %RSD) below 5% in all cases. The developed method is simple, easy, and low cost for the analysis of two herbicides potentially dangerous for environmental and human health. Graphical abstract.

Metástasis cutáneas: como manifestación inicial y de recidiva de cáncer de mama: a propósito de un caso / Cutaneous metastasis as inicial and recurrence manifestation of breast cancer: a case report

INTRODUCCIÓN: Las metástasis cutáneas (MC) son un fenómeno poco frecuente en pacientes que padecen de cáncer de origen visceral, en mujeres se deben principalmente al cáncer de mama (CDM). Las MC se pueden presentar como manifestación de un cáncer avanzado o como signo de recidiva de un cáncer en remisión. La presentación clínica de un CDM en piel es muy variada, al estar presente es un indicador de enfermedad avanzada y , a su vez, de mal pronóstico, donde la variante clínica nodular es la más representativa. PRESENTACIÓN DEL CASO: Paciente femenina, 58 años. Con historia en 2005 de MC como primera manifestación de CDM. Presentó evolución satisfactoria y regresión de MC posterior a tratamiento con quimioterapia y radioterapia. Se resolvió quirúrgicamente, asociado a terapia hormonal, continuando en control ambulatorio. En 2018 consulta por lesión cutánea en pierna derecha, donde se constató además lesión cutánea mamaria izquierda. Se realizó biopsia de ambas lesiones que informó carcinoma epidermoide in situ en pierna derecha y metástasis dérmica de carcinoma ductal mamario con extensión intraepidérmica en zona mamaria izquierda y cervical ipsilateral. DISCUSIÓN: Las MC generalmente son precedidas por el diagnóstico de tumor mamario, rara vez son primera manifestación de él. De las MC cuya aparición es posterior al hallazgo de CDM, pueden observarse lesiones incluso al cabo de 10 años, lo que ha llevado a afirmar que el riesgo de enfermedad a distancia estará presente durante el resto de la vida. La presencia de MC por CDM implica generalmente amplia diseminación de la enfermedad, por lo tanto tener en cuenta este diagnóstico sería de gran ayuda en cuanto a oportunidad de tratamiento.

INTRODUCTION: Cutaneous metastases (MC) are a rare phenomenon in patients suffering from visceral cancer, in women they are mainly due to breast cancer (CDM). MC can occur as a manifestation of advanced cancer or as a sign of recurrence of a cancer in remission. The clinical presentation of a CDM in skin is very varied, being present is an indicator of advanced disease and, in turn, of poor prognosis, where the nodular clinical variant is the most representative. PRESENTATION OF THE CASE: Female patient, 58 years old. With history in 2005 of MC as the first manifestation of BC. After treatment with chemo and radiotherapy she presented satisfactory evolution and regression of CM. It was resolved later with surgery and hormonal therapy, continuing in ambulatory control. In 2018, the patient complained of a cutaneous lesion in the right leg. Physical exam also revealed a left mammary skin lesion. Biopsy was performed on both lesions. It reported carcinoma in situ in the right leg and dermal metastasis of mammary ductal carcinoma with intraepidermal extension in the left mammary and cervical area. DISCUSSION: CM are generally found after discovering the mammary tumor, they are rarely its first manifestation. As late manifestation of the disease, CM have been reported up to ten years later. The presence of MC by CDM generally implies a broad dissemination of the disease, taking into account this diagnosis could be of great help in terms of an opportunity for treatment.

SGLT2 inhibitors as add on therapy in type 2 diabetes: a real world study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a progressive chronic disease associated with severe microvascular and macrovascular complications. Our aim is to assess the real world effectiveness of SGT" inhibitors in achieving metabolic therapeutic goals. METHODS: A retrospective, observational study. Inclusion criteria for patients were a previous diagnosis of type 2 diabetes mellitus, age > 18 years, patients receiving either dapagliflozin 10 mg and/or canagliflozin 300 mg. We excluded pregnant patients, patients with type 1 diabetes mellitus and acute metabolic complications of diabetes. Patients included in the analysis were enrolled in a health plan at least 6 months prior to the index date (baseline period) and in the 6 months following the index date (follow-up period). Achievement of glycated hemoglobin goals were established as <7%. RESULTS: We screened 2870 Mexican patients; 288 (10.03% received SGLT2 inhibitors). Mean age for both groups of patients was 57.68 ± 11.06 years. The dapagliflozin control rate was 19.56% and the canagliflozin control rate 18.96%. Monotherapy with SGLT2 inhibitors was used in 21 patients (6.25%). Overall HbA1c goals were met in 56 patients (19.44%) with similar results with dapagliflozin or canagliflozin. The combination of SGLT2 inhibitors and sulfonylureas had the highest control rate (30.30%) compared to other regimens. Monotherapy was present in 6.25%. Insulin requirement was associated with poor control (2.8% vs. 18.05%, P < 0.05, 95% CI [0.07, 0.84]). Combination therapy with DPP4 inhibitors was associated with better control (P < 0.05, 95% CI, [1.10, 3.92]). CONCLUSION: No difference between the drugs was observed. Real-world effectiveness data of SGLT2 inhibitors show that the percentage of patients reaching metabolic goals is low. SLGT2 inhibitors were used more frequently as combined therapy.

Spanish Society of Vascular and Interventional Radiology (SERVEI) Bibliometric Study (2010-2015): What, How, and Where do Spanish Interventional Radiologists Publish?

PURPOSE: We analyzed the scientific production of members of the Spanish Society of Vascular and Interventional Radiology (SERVEI) from 2010 to 2015. MATERIALS AND METHODS: We retrospectively analyzed the indexed scientific productivity of all SERVEI members for the last 6 years as measured by bibliometric indexes. Different databases were used (e.g., PubMed, Scopus, Web of Knowledge) to retrieve the total number of publications, number of citations, and h-index. Every article was assigned the impact factor of its publication year and its corresponding quartile according to Journal Citation Reports. The relationships between all of these parameters and the Spanish region, the gender and age of the interventional radiologists (IRs), and their connection to the university environment were also studied. RESULTS: A total of 519 scientific articles from 247 SERVEI members working in 118 Spanish hospitals were included, an average of 0.3 articles per interventionist/year. Most of the manuscripts were published in impact journals (52.2%) and placed in the lowest quartile (Q4). Navarre, Aragon, and Catalonia were the regions with the highest publication rate during the period studied (1.7, 0.92, and 0.6 publications per interventionist/year, respectively). Only 57 articles (12.6%) were published in 11 of the 125 journals under the category of Radiology, Nuclear Medicine, and Medical Imaging according to JCR. CONCLUSIONS: The scientific production of the Spanish IRs in the last 6 years is difficult to interpret. However, more than 50% of IRs published one article in the last 6 years. Finally, it would be advisable to repeat this study over a period of time in order to compare.

The kinase inhibitors R406 and GS-9973 impair T cell functions and macrophage-mediated anti-tumor activity of rituximab in chronic lymphocytic leukemia patients.

Small molecules targeting kinases involved in B cell receptor signaling are showing encouraging clinical activity in chronic lymphocytic leukemia (CLL) patients. Fostamatinib (R406) and entospletinib (GS-9973) are ATP-competitive inhibitors designed to target spleen tyrosine kinase (Syk) that have shown clinical activity with acceptable toxicity in trials with CLL patients. Preclinical studies with these inhibitors in CLL have focused on their effect in patient-derived leukemic B cells. In this work we show that clinically relevant doses of R406 and GS-9973 impaired the activation and proliferation of T cells from CLL patients. This effect could not be ascribed to Syk-inhibition given that we show that T cells from CLL patients do not express Syk protein. Interestingly, ζ-chain-associated protein kinase (ZAP)-70 phosphorylation was diminished by both inhibitors upon TCR stimulation on T cells. In addition, we found that both agents reduced macrophage-mediated phagocytosis of rituximab-coated CLL cells. Overall, these results suggest that in CLL patients treated with R406 or GS-9973 T cell functions, as well as macrophage-mediated anti-tumor activity of rituximab, might be impaired. The potential consequences for CLL-treated patients are discussed.

Expresión y renaturalización del antígeno protector de Bacillus anthracis: un modelo para evaluar el replegado de proteínas antigénicas recombinantes a gran escala / Expression and refolding of the protective antigen of Bacillus anthracis: A model for high-throughput screening of antigenic recombinant protein refolding

Bacillus anthracis protective antigen (PA) is a well known and relevant immunogenic protein that is the basis for both anthrax vaccines and diagnostic methods. Properly folded antigenic PA is necessary for these applications. In this study a high level of PA was obtained in recombinant Escherichia coli. The protein was initially accumulated in inclusion bodies, which facilitated its efficient purification by simple washing steps; however, it could not be recognized by specific antibodies. Refolding conditions were subsequently analyzed in a high-throughput manner that enabled nearly a hundred different conditions to be tested simultaneously. The recovery of the ability of PA to be recognized by antibodies was screened by dot blot using a coefficient that provided a measure of properly refolded protein levels with a high degree of discrimination. The best refolding conditions resulted in a tenfold increase in the intensity of the dot blot compared to the control. The only refolding additive that consistently yielded good results was L-arginine. The statistical analysis identified both cooperative and negative interactions between the different refolding additives. The high-throughput approach described in this study that enabled overproduction, purification and refolding of PA in a simple and straightforward manner, can be potentially useful for the rapid screening of adequate refolding conditions for other overexpressed antigenic proteins.

El antígeno protector de Bacillus anthracis (protective antigen, PA) es una importante proteína inmunogénica, en la que se basan tanto las vacunas contra el ántrax/carbunclo como varios métodos diagnósticos. Para estas aplicaciones es esencial que el PA mantenga sus propiedades antigénicas, para lo cual debe estar correctamente plegado. En este estudio se obtuvieron altos niveles del PA en Escherichia coli recombinante. Inicialmente, la proteína se acumuló desnaturalizada en cuerpos de inclusión, lo que facilitó su eficiente purificación en simples pasos de lavado, pero no fue reconocida por anticuerpos específicos. Se analizaron las condiciones de replegado con un sistema de alto rendimiento, evaluando simultáneamente casi un centenar de condiciones diferentes. La recuperación de la capacidad del PA de ser reconocido por los anticuerpos se evaluó por dot blot utilizando un coeficiente que proporcionó una medida de los niveles de proteína correctamente plegada, con un alto grado de discriminación. Las mejores condiciones de renaturalización permitieron un aumento de diez veces en la intensidad de los dot blots con respecto del control. El único aditivo que produjo buenos resultados de forma constante fue la L-arginina. El análisis estadístico de las interacciones entre los diferentes aditivos de replegado permitió identificar tanto interacciones cooperativas como negativas. El enfoque de alto rendimiento descripto en este trabajo, que permitió la sobreproducción, purificación y plegado del PA de una manera sencilla y directa, puede ser potencialmente útil para el rápido screening de las condiciones adecuadas de replegado cuando se sobreexpresan otras proteínas antigénicas.

Expression and refolding of the protective antigen of Bacillus anthracis: A model for high-throughput screening of antigenic recombinant protein refolding.

Bacillus anthracis protective antigen (PA) is a well known and relevant immunogenic protein that is the basis for both anthrax vaccines and diagnostic methods. Properly folded antigenic PA is necessary for these applications. In this study a high level of PA was obtained in recombinant Escherichia coli. The protein was initially accumulated in inclusion bodies, which facilitated its efficient purification by simple washing steps; however, it could not be recognized by specific antibodies. Refolding conditions were subsequently analyzed in a high-throughput manner that enabled nearly a hundred different conditions to be tested simultaneously. The recovery of the ability of PA to be recognized by antibodies was screened by dot blot using a coefficient that provided a measure of properly refolded protein levels with a high degree of discrimination. The best refolding conditions resulted in a tenfold increase in the intensity of the dot blot compared to the control. The only refolding additive that consistently yielded good results was L-arginine. The statistical analysis identified both cooperative and negative interactions between the different refolding additives. The high-throughput approach described in this study that enabled overproduction, purification and refolding of PA in a simple and straightforward manner, can be potentially useful for the rapid screening of adequate refolding conditions for other overexpressed antigenic proteins.

Anatomical variations in the aortic bifurcation in new zealand white rabbits on arteriography.

The radiologic anatomy of the aortic bifurcation in the rabbit has received little study but it is important as this anatomical area is widely used in atherosclerosis research. Thirty rabbits were used to study the aortic bifurcation and subsequent branching patterns on arteriography. Fifteen different arteries were identified. Mean arterial diameters of 2.88 ± 0.7 and 2.27 ± 0.55 mm were obtained for the aorta and external iliac arteries, respectively. The cranial and middle aspects at the seventh lumbar vertebra (L7) were the most frequent anatomical landmarks (53.3% of the cases) for aortic and common iliac bifurcations, respectively. The caudal aspect of L6 was the most frequent origin (50% of the cases) for the median sacral artery. Deep circumflex iliac arteries originated from common iliac arteries and not the abdominal aorta in the rabbit, showing anatomical asymmetry in 73.3% of the cases. No gender disparity was found in the anatomical location of any of the arteries of the study. Knowledge of normal vascular landmarks for the aortic bifurcation as well as anatomical variations should be helpful to future experimental studies.

Resección toracoscópica de nódulo pulmonar solitario en escolar / Thoracoscopic resection of solitary pulmonary nodule school

La cirugía mínima invasiva constituye uno de los grandes avances de la medicina en las tres últimas décadas. La cirugía pediátrica no ha escapado a este progreso, y hoy en día son muchas las indicaciones de esta técnica en el niño. El nódulo pulmonar solitario se define como una lesión esférica rodeada por parénquima sano, no asociada a atelectasia y sin adenopatías mediastinales, Se reporta el caso deescolar femenino de 9 años de edad quien presentó evidencia radiológica de nódulo pulmonar solitario ubicado a nivel de la base del campo pulmonar derecho. Se realizó resección toracoscópica del mismo. Fueron descartadas patologías oncológicas, tuberculosis, micosis y enfermedades de depósito. Únicamente fue positiva la serología para Chlamydia pneumoniae (IgM), sin embargo, la pacientenunca presento clínica de infección respiratoria baja antes de su ingreso. La biopsia evidenció una lesión inflamatoria encapsulada inespecífica. Se concluye que la toracoscópia debe ser el método de primera elección ante cualquier lesión torácica y a cualquier edad enpediatría

Minimally invasive surgery constitutes one of the greatest advances of medicine in the last three decades. Pediatric surgery has not escaped this progress; in fact, nowadays there are many indications to perform this technique on children. Solitary pulmonary nodule is defined as a spherical lesion surrounded by healthy parenchyma, not associated with atelectasia and without mediastinallymphadenopathy. We present a nine-year-old girl, with radiological evidence of a solitary pulmonary nodule located at base of the right lung field. A thoracoscopic resection was performed. Oncological pathologies, tuberculosis, mycosis and deposit illnesses werediscarded. The only positive serology was for Chlamydia pneumoniae (IgM); however, the patient never presented clinical lower respiratory infection before her admission. The biopsy determined an encapsulated nonspecific inflammatory lesion. We conclude thatthoracoscopy should be the method of choice for any thoracic injury in children

Presentación de un caso clínico de atrofia multisistémica y actualización de criterios diagnósticos / Multisystem atrophy and diagnostic criteria updating: A clinical case presentation

La atrofia multisistémica constituye un trastorno neurodegenerativo esporádico de etiología no precisada que se caracteriza por parkinsonismo, trastornos cerebelosos, disfunción autonómica y piramidalismo; los hallazgos patológicos comprenden pérdida celular y gliosis en las neuronas estriatonígricas, olivopontocerebelosas y autonómicas; y la presencia de inclusiones intracitoplasmáticas oligodendrogliales y neuronales, ubiquitina, tau y alfasinucleína positivas. Afecta tanto a hombres como a mujeres, con inicio en la sexta década de la vida como promedio y una prevalencia de 4/100 000. Se presentaron los últimos criterios diagnósticos de atrofia multisistémica y el caso clínico de un paciente de 65 años con un cuadro progresivo, de 4 años de evolución, ataxia cerebelosa progresiva, síndrome rígido acinético, disfunción autonómica, signos piramidales y mala respuesta a la levodopa, con imágenes de resonancia magnética que muestran atrofia de vermis, hemisferios cerebelosos, tallo cerebral (puente) e hipointensidad de ambas regiones putaminales en t2. Se concluyó el caso con el diagnóstico de atrofia multisistémica tipo C

The multisystem atrophy is a sporadic neurodegenerative disorder of unknown origin characterized by parkinsonism, cerebellar disorders, autonomic dysfunction and pyramidal disease, provoked by a cellular loss and gliosis in the nigrostriatal, olivopontocerebellar and autonomic neurons and the presence of oligodendroglia and neuronal intracytoplasmic positive inclusions, ubiquitin, tau and alpha-sinuclein affecting men and women starting as average during the sixth decade of life and a prevalence of 4/100 000. The last diagnostic criteria of multisystem atrophy were showed as well as the clinical case of a patient aged 65 with a progressive picture of 4 years of evolution, progressive cerebellar ataxia, a rigid akinetic syndrome autonomic dysfunction, pyramidal signs and a poor response to levodopa with magnetic resonance images showing vermis atrophy, cerebellar hemispheres, cerebral stem (bridge) and hipointensity of both putamen regions in T2. We conclude that case was diagnosed with type C multisystem atrophy

Cateterización bilateral de los senos petrosos inferiores: utilidad en el síndrome de cushing / Bilateral catheterization of inferior petrosal sinous: utility in cushing’ syndrome

Objetivo: Presentar la experiencia de los autores en el cateterismo bilateral y simultáneo de los senos petrosos inferiores (SPI) en pacientes con síndrome de Cushing dependientes de la hormona adrenocorticotropa (ACTH ). Material y método: Un estudio retrospectivo desde enero de 2003 hasta septiembre de 2009 con nueve pacientes (dos hombres y siete mujeres) diagnosticados con síndrome de Cushing y ACTH dependientes. Se cateterizaron simultáneamente los senos petrosos inferiores, estudiando la ACTH basal y tras un estímulo con la CRH, a fin de medir los gradientes intrahipofisarios y en sangre periférica. La sospecha diagnóstica se realizó por concentraciones inapropiadas y persistentemente elevadas de cortisol plasmático y del cortisol libre urinario; así como por ausencia de supresión con la dexametasona. En todos, salvo uno, las pruebas de imagen fueron negativas. Resultados: La cateterización fue exitosa y sin complicaciones. Hubo un diagnóstico definitivo en todos los casos. Conclusión: En los pacientes seleccionados, la cateterización de los SPI fue un procedimiento eficiente en el diagnóstico diferencial del síndrome de Cushing y en la localización intrahipofisaria de la secreción de ACTH.

Objective: The aim of this study is to present our experience on bilateral and simultaneous inferior petrous sinus catheterization, on those patients with ACTH -dependent Cushing’s sydrome. We describe the procedure and our results. Material and Method: A retrospective study was held between January 2003 and September 2009, including nine patients (2 men, 7 women) presenting ACTH -dependentCushing’s syndrome. Simultaneous inferior petrosal sinus catheterization was performed in all of them, sampling basal ACTH and after CRH stimulation. ACTH levels gradient in different pituitary locations and peripheral blood levels was recorded. Diagnosis was suggested when inappropriate and maintained hypercortisolemia. High urinary free cortisol levels and no response to dexamethasone suppressionwere detected. Eight out of nine patients had a prior negative imaging test result. Results: Inferior petrosal sinus bilateral catheterization was successfully performed in all cases, with no evidence of further complications. The results showed definitive diagnosis in all cases. In four patients ACTH levels gradient was lateralized to the left, leading to a specific surgical approach. One patient presented pituitary ACTH -secreting adenoma. Two other patients showed ectopic ACTH production, one showedsuprarenal adenoma secreting ACTH and other one showed response to pituitary stimulation without side lateralisation, presenting a histological diagnosis of pituitary hyperplasia. Conclusion: Petrosal sinus catheterization is shown to be an efficient procedure to manage Cushing’s syndrome differential diagnosis and to obtain specific anatomical information.