Access-Site Complications in Mechanical Thrombectomy for Acute Ischemic Stroke: A Review of Prospective Trials.

BACKGROUND: A shift has occurred in interventional cardiology from transfemoral to transradial access due to a 70%-80% decrease in complications. This shift has not yet taken place in other interventional specialties, perhaps owing to the lack of generalizability of findings in the cardiology data. PURPOSE: Our aim was to assess data from the recent mechanical thrombectomy prospective trials to better understand the access-site complication rate. DATA SOURCES: Articles were systematically sourced from the National Center for Biotechnology Information PubMed archive. STUDY SELECTION: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, prospective, randomized controlled trials published after 2008 with mention of major and/or minor femoral access-site complications in neuroendovascular mechanical thrombectomies were included. DATA ANALYSIS: Major and minor femoral access-site complications were extracted. A total complication rate was calculated with major access-site complications alone and combined with minor access-site complications. DATA SYNTHESIS: Seven prospective studies of 339 total screened met the inclusion criteria. Eleven major access-site complications were identified in of 660 total interventions, revealing a major access-site complication rate of 1.67% for patients undergoing mechanical thrombectomy with transfemoral access. If minor access-site complications were included, 35 total incidents were detected in 763 interventions, resulting in a total complication rate of 4.59%. LIMITATIONS: Multiple unspecified vessel and procedure-related complications were mentioned in the studies. CONCLUSIONS: The overall rate of major access-site complications was 1.67% in this review, which is not low and poses a risk to patients. We suggest further investigation into the feasibility and complication rates of alternative access sites for neurointerventional procedures.

Inhibition of autophagy sensitizes malignant pleural mesothelioma cells to dual PI3K/mTOR inhibitors.

Malignant pleural mesothelioma (MPM) originates in most of the cases from chronic inflammation of the mesothelium due to exposure to asbestos fibers. Given the limited effect of chemotherapy, a big effort is being made to find new treatment options. The PI3K/mTOR pathway was reported to be upregulated in MPM. We tested the cell growth inhibition properties of two dual PI3K/mTOR inhibitors NVP-BEZ235 and GDC-0980 on 19 MPM cell lines. We could identify resistant and sensitive lines; however, there was no correlation to the downregulation of PI3K/mTOR activity markers. As a result of mTOR inhibition, both drugs efficiently induced long-term autophagy but not cell death. Autophagy blockade by chloroquine in combination with the dual PI3K/mTOR inhibitors significantly induced caspase-independent cell death involving RIP1 in the sensitive cell line SPC212. Cell death in the resistant cell line Mero-82 was less pronounced, and it was not induced via RIP1-dependent mechanism, suggesting the involvement of RIP1 downstream effectors. Cell death induction was confirmed in 3D systems. Based on these results, we identify autophagy as one of the main mechanisms of cell death resistance against dual PI3K/mTOR inhibitors in MPM. As PI3K/mTOR inhibitors are under investigation in clinical trials, these results may help interpreting their outcome and suggest ways for intervention.

In vitro differentiation of near-unlimited numbers of functional mouse basophils using conditional Hoxb8.

BACKGROUND: Basophils constitute a rare leukocyte population known for their effector functions in inflammation and allergy, as well as more recently described immunoregulatory roles. Besides their low frequency, functional analysis of basophils is hindered by a short life span, inefficient ex vivo differentiation protocols, and lack of suitable cell models. A method to produce large quantities of basophils in vitro would facilitate basophil research and constitute a sought-after tool for diagnostic and drug testing purposes. METHODS: A method is described to massively expand bone marrow-derived basophils in vitro. Myeloid progenitors are conditionally immortalized using Hoxb8 in the presence of interleukin-3 (IL-3) and outgrowing cell lines selected for their potential to differentiate into basophils upon shutdown of Hoxb8 expression. RESULTS: IL-3-dependent, conditional Hoxb8-immortalized progenitor cell lines can be expanded and maintained in culture for prolonged periods. Upon shutdown of Hoxb8 expression, near-unlimited numbers of mature functional basophils can be differentiated in vitro within six days. The cells are end-differentiated and short-lived and express basophil-specific surface markers and proteases. Upon IgE- as well as C5a-mediated activation, differentiated basophils release granule enzymes and histamine and secrete Th2-type cytokines (IL-4, IL-13) and leukotriene C4. IL-3-deprivation induces apoptosis correlating with upregulation of the BH3-only proteins BCL-2-interacting mediator of cell death (BIM) and p53 upregulated modulator of apoptosis (PUMA) and downregulation of proviral integration site for Moloney murine leukemia virus 1 kinase (PIM-1). CONCLUSION: A novel method is presented to generate quantitative amounts of mouse basophils in vitro, which moreover allows genetic manipulation of conditionally immortalized progenitors. This approach may represent a useful alternative method to isolating primary basophils.

Intracellular localization of the BCL-2 family member BOK and functional implications.

The pro-apoptotic BCL-2 family member BOK is widely expressed and resembles the multi-BH domain proteins BAX and BAK based on its amino acid sequence. The genomic region encoding BOK was reported to be frequently deleted in human cancer and it has therefore been hypothesized that BOK functions as a tumor suppressor. However, little is known about the molecular functions of BOK. We show that enforced expression of BOK activates the intrinsic (mitochondrial) apoptotic pathway in BAX/BAK-proficient cells but fails to kill cells lacking both BAX and BAK or sensitize them to cytotoxic insults. Interestingly, major portions of endogenous BOK are localized to and partially inserted into the membranes of the Golgi apparatus as well as the endoplasmic reticulum (ER) and associated membranes. The C-terminal transmembrane domain of BOK thereby constitutes a 'tail-anchor' specific for targeting to the Golgi and ER. Overexpression of full-length BOK causes early fragmentation of ER and Golgi compartments. A role for BOK on the Golgi apparatus and the ER is supported by an abnormal response of Bok-deficient cells to the Golgi/ER stressor brefeldin A. Based on these results, we propose that major functions of BOK are exerted at the Golgi and ER membranes and that BOK induces apoptosis in a manner dependent on BAX and BAK.

Espectro imaginológico de las infecciones pulmonares en pacientes trasplantados / The imaging spectrum of pulmonary infections in transplant patients

Las infecciones son comunes en los pacientes luego de un trasplante de médula ósea y de un órgano sólido. El pulmón es uno de los órganos más afectados. Se deben conocer los gérmenes más frecuentes que lo afectan, teniendo en cuenta su tiempo de aparición, en busca de orientar la conducta clínica y obtener un diagnóstico acertado. En el presente artículo se revisan las manifestaciones imaginológicas más comunes de cada uno de los gérmenes implicados y su relación temporal, según el tipo de trasplante realizado.

BCL-2 family member BOK is widely expressed but its loss has only minimal impact in mice.

BOK/MTD was discovered as a protein that binds to the anti-apoptotic Bcl-2 family member MCL-1 and shares extensive amino-acid sequence similarity to BAX and BAK, which are essential for the effector phase of apoptosis. Therefore, and on the basis of its reported expression pattern, BOK is thought to function in a BAX/BAK-like pro-apoptotic manner in female reproductive tissues. In order to determine the function of BOK, we examined its expression in diverse tissues and investigated the consequences of its loss in Bok(-/-) mice. We confirmed that Bok mRNA is prominently expressed in the ovaries and uterus, but also observed that it is present at readily detectable levels in several other tissues such as the brain and myeloid cells. Bok(-/-) mice were produced at the expected Mendelian ratio, appeared outwardly normal and proved fertile. Histological examination revealed that major organs in Bok(-/-) mice displayed no morphological aberrations. Although several human cancers have somatically acquired copy number loss of the Bok gene and BOK is expressed in B lymphoid cells, we found that its deficiency did not accelerate lymphoma development in Eµ-Myc transgenic mice. Collectively, these results indicate that Bok may have a role that largely overlaps with that of other members of the Bcl-2 family, or may have a function restricted to specific stress stimuli and/or tissues.

Bocio en ninos y adolescentes: estudio de tiroiditis de Hashimoto mediante biopsia tiroidea por aspiracion / Goiter in children and adolescents: study of thyroiditis of Hashimoto with thyriod aspiration biopsy

Se estudiaron 103 pacientes con edades entre 4 y 16 anos, portadores de bocio difuso mediante biopsia tiroidea por aspiracion, con el fin de tratar de establecer la incidencia de tiroiditis de Hashimoto en estos grupos etarios en Medellin. Se emplearon para el diagnostico citologico de esta entidad los criterios de clasificacion del Manual for Nutritional Survey del Interdepartamental Comitee of Nutritin for national Defense (ICNND). El 69.9% fueron portadores de bocio grado I, el 28.1% presentaron gradoII y unicamente el 1.9% grado III. Ninguno fue portador de bocio grado IV. En 4 pacientes (3.8%) se hizo el diagnostico de tiroiditis de Hashimoto, en dos de neoplasia folicular y en los restantes de bocio coloide o nodular. Unicamente en un nino se encontro hipotiroidismo en las pruebas de laboratorio y en el el diagnostico histopatologico fue tiroiditis de Hashimoto. De los cuatro pacientes que presentaron tiroiditis de Hashimito tres eran mujeres y tres tenian bocio grado II y el otro grado I. De los 73 en quienes se habia anotado en el protocolo esta informacion, 58 (56.3%) presentaron historia familiar de enfermedad tiroidea. En 13 (12.6%) de los 103 pacientes no se obtuvo material de biopsia suficiente para diagnostico en el primer intento por lo cual se repitio el procedimiento. No se presento ninguna complicacion. Como en trabajos anteriores se encontro en esta investigacion que la biopsia tiroidea por aspiracion puede ser de gran valor en el diagnostico de tiroiditis de Hashimoto y para estudiar la incidencia de esta enfermedad en ciertas poblaciones...

Tiroiditis linfocitica subaguda no dolorosa: presentacion de nueve casos / Painless subacute lymphocytic thyroiditis: presentation of 9 cases

Se informan 9 casos de tiroiditis linfocitica subaguda no dolorosa, cuyas edades oscilaron entre 14 y 42 anos con un promedio de 32.5. Todos tuvieron bocio moderado y disfuncion tiroidea discreta, diagnosticada por vclinica y laboratorio, desaparicion aguda, que remitio espontaneamente en el curso de la evolucion. Cinco presentaron hipertiroidismo con duracion entre 6 a 12 meses con un promedio de 10.2 meses y las otras cuatro, hipotiroidismo con duracion entre 6 y 12 meses, promedio de 10.2. Como caracteristicas de la entidad todas las pacientes presentaron una captacion tiroidea de I 131 ausente, sin causa conocida, en presencia de hiper o hipotiroidismo. En 6 de las 9 pacientes se practico biopsia tiroidea por aspiracion; en 4 la histologia fue sugestiva de tiroiditis de Hashimoto lo que confirmaba aun mas el diagnostico de tiroiditis linfocitica subaguda no dolorosa. Es dificil, si no imposible realizar el diagnostico diferencial entre estas 2 tiroiditis con biopsia por aspiracion (2,5);ambas pueden presentar infiltracion linfocitica, celulas de Hurthle, centros germinativos de linfociticos y cierto grado de fibrosis, siendo estos hallazgos mas intensos en la tiroiditis de Hashimoto en las biopsias tiroideas de nuestros casos 3,4,8,9, en presencia de captacion tiroidea de I 131 ausente, confirma el diagnostico de tiroiditis linfocitica subaguda no dolorosa. Creemos que es la primera vez en la literatura colombiana que se informan casos de esta entidad.

Tratamiento de la tirotoxicosis con 131-I: estudio de 124 pacientes / Treatment of thyrotoxicosis with I-131: study of 124 patients

Se revisaron las historias de 124 pacientes hipertiroideos tratados con I en la Seccion de Medicina Nuclear, Hospital Universitario San Vicente de Paul (HUSVP) desde 1980 hasta octubre de 1985; se incluyeron unicamente las que tenian datos adecuados. Los pacientes pertenecian a la consulta externa del HUSVP y del ISS. La gran mayoria fueron tratados con tapazol y propranolol por semanas o meses, antes de ordenar yodo radioactivo; algunos recibieron propranolol unicamente a dosis altas por no conseguirse tapazol. A todos se les practico gamagrafia tiroidea y captacion a las 4 y 24 horas con I sin estar recibiendo metimazol, previa a la administracion de este radioisotopo. Se calculo la dosis en la enfermedad de Graves con base en 80 microcuries por gramo de glandula tiroidea y en el bocio multinodular y adenoma toxico con base en 100 o 150. El peso de la glandula se calculo por palpacion. 91% de los pacientes fueron mujeres y las decadas mas comprometidas fueron entre la 3a y la 5a, mas tempranamente en la enfermedad de Graves. El 88.7 fue portador de una enfermedad de Graves, el 1.6% de bocio multinodular y el 9.6% de un adenoma toxico. La dosis promedio de yodo radioactivo de la enfermedad de Graves fue de 8.42 +- 1.41 milicuries y en el adenoma toxico de 12.67 +- 5.15. Sin discriminar la variedad de hipertiroidismo, el 60.4% se curo con una dosis unica de radiofarmaco; e;l 11.2% necesito dos dosis y el 2.4% tres dosis. No se conocio el evolucion final de 32 pacientes...