A novel approach to guide GD2-targeted therapy in pediatric tumors by PET and [64Cu]Cu-NOTA-ch14.18/CHO.

Background: The tumor-associated disialoganglioside GD2 is a bona fide immunotherapy target in neuroblastoma and other childhood tumors, including Ewing sarcoma and osteosarcoma. GD2-targeting antibodies proved to be effective in neuroblastoma and GD2-targeting chimeric antigen receptors (CAR)- expressing T cells as well as natural killer T cells (NKTs) are emerging. However, assessment of intra- and intertumoral heterogeneity has been complicated by ineffective immunohistochemistry as well as sampling bias in disseminated disease. Therefore, a non-invasive approach for the assessment and visualization of GD2 expression in-vivo is of upmost interest and might enable a more appropriate treatment stratification. Methods: Recently, [64Cu]Cu-NOTA-ch14.18/CHO (64Cu-GD2), a radiolabeled GD2-antibody for imaging with Positron-Emission-Tomography (PET) was developed. We here report our first clinical patients' series (n = 11) in different pediatric tumors assessed with 64Cu-GD2 PET/MRI. GD2-expression in tumors and tissue uptake in organs was evaluated by semiquantitative measurements of standardized uptake values (SUV) with PET/MRI on day 1 p.i. (n = 11) as well as on day 2 p.i. (n = 6). Results: In 8 of 9 patients with suspicious tumor lesions on PET/MRI at least one metastasis showed an increased 64Cu-GD2 uptake and a high tracer uptake (SUVmax > 10) was measured in 4 of those 8 patients. Of note, sufficient image quality with high tumor to background contrast was readily achieved on day 1. In case of 64Cu-GD2-positive lesions, an excellent tumor to background ratio (at least 6:1) was observed in bones, muscles or lungs, while lower tumor to background contrast was seen in the spleen, liver and kidneys. Furthermore, we demonstrated extensive tumor heterogeneity between patients as well as among different metastatic sites in individual patients. Dosimetry assessment revealed a whole-body dose of only 0.03 mGy/MBq (range 0.02-0.04). Conclusion: 64Cu-GD2 PET/MRI enables the non-invasive assessment of individual heterogeneity of GD2 expression, which challenges our current clinical practice of patient selection, stratification and immunotherapy application scheme for treatment with anti-GD2 directed therapies.

Image Quality and Quantitative PET Parameters of Low-Dose [18F]FDG PET in a Long Axial Field-of-View PET/CT Scanner.

PET/CT scanners with a long axial field-of-view (LAFOV) provide increased sensitivity, enabling the adjustment of imaging parameters by reducing the injected activity or shortening the acquisition time. This study aimed to evaluate the limitations of reduced [18F]FDG activity doses on image quality, lesion detectability, and the quantification of lesion uptake in the Biograph Vision Quadra, as well as to assess the benefits of the recently introduced ultra-high sensitivity mode in a clinical setting. A number of 26 patients who underwent [18F]FDG-PET/CT (3.0 MBq/kg, 5 min scan time) were included in this analysis. The PET raw data was rebinned for shorter frame durations to simulate 5 min scans with lower activities in the high sensitivity (HS) and ultra-high sensitivity (UHS) modes. Image quality, noise, and lesion detectability (n = 82) were assessed using a 5-point Likert scale. The coefficient of variation (CoV), signal-to-noise ratio (SNR), tumor-to-background ratio (TBR), and standardized uptake values (SUV) including SUVmean, SUVmax, and SUVpeak were evaluated. Subjective image ratings were generally superior in UHS compared to the HS mode. At 0.5 MBq/kg, lesion detectability decreased to 95% (HS) and to 98% (UHS). SNR was comparable at 1.0 MBq/kg in HS (5.7 ± 0.6) and 0.5 MBq/kg in UHS (5.5 ± 0.5). With lower doses, there were negligible reductions in SUVmean and SUVpeak, whereas SUVmax increased steadily. Reducing the [18F]FDG activity to 1.0 MBq/kg (HS/UHS) in a LAFOV PET/CT provides diagnostic image quality without statistically significant changes in the uptake parameters. The UHS mode improves image quality, noise, and lesion detectability compared to the HS mode.

Repurposing the mucolytic agent ambroxol for treatment of sub-acute and chronic ischaemic stroke.

Ambroxol is a well-known mucolytic expectorant, which has gained much attention in amyotrophic lateral sclerosis, Parkinson's and Gaucher's disease. A specific focus has been placed on ambroxol's glucocerebrosidase-stimulating activity, on grounds that the point mutation of the gba1 gene, which codes for this enzyme, is a risk factor for developing Parkinson's disease. However, ambroxol has been attributed other characteristics, such as the potent inhibition of sodium channels, modification of calcium homeostasis, anti-inflammatory effects and modifications of oxygen radical scavengers. We hypothesized that ambroxol could have a direct impact on neuronal rescue if administered directly after ischaemic stroke induction. We longitudinally evaluated 53 rats using magnetic resonance imaging to examine stroke volume, oedema, white matter integrity, resting state functional MRI and behaviour for 1 month after ischemic stroke onset. For closer mechanistic insights, we evaluated tissue metabolomics of different brain regions in a subgroup of animals using ex vivo nuclear magnetic resonance spectroscopy. Ambroxol-treated animals presented reduced stroke volumes, reduced cytotoxic oedema, reduced white matter degeneration, reduced necrosis, improved behavioural outcomes and complex changes in functional brain connectivity. Nuclear magnetic resonance spectroscopy tissue metabolomic data at 24 h post-stroke proposes several metabolites that are capable of minimizing post-ischaemic damage and that presented prominent shifts during ambroxol treatment in comparison to controls. Taking everything together, we propose that ambroxol catalyzes recovery in energy metabolism, cellular homeostasis, membrane repair mechanisms and redox balance. One week of ambroxol administration following stroke onset reduced ischaemic stroke severity and improved functional outcome in the subacute phase followed by reduced necrosis in the chronic stroke phase.

Acquired Immune Deficiency Syndrome Cholangiopathy: Case Series of Three Patients and Literature Review.

Cholangiopathy in acquired immune deficiency syndrome (AIDS) is being less frequently reported since antiretroviral therapy (ART) is available. It is associated with an advanced disease and seen in situations with poor access or non-compliance with ART. Liver biopsy is thought to have low yield in cases of AIDS cholangiopathy, but it can be an important tool in diagnosis, especially early in the course of the disease. The prognosis of AIDS cholangiopathy is generally not favorable, the therapy for opportunistic infections is mostly ineffective and restoration of immune system with ART remains the therapy of choice. We are sharing our experience of diagnosing and managing three cases of AIDS cholangiopathy.

Aerococcus urinae: A Rare Cause of Endocarditis Presenting With Acute Stroke.

Aerococcus urinae is a rare organism infrequently isolated from cultures. Mostly known to cause urinary tract infection, it can cause bacteremia leading to severe urosepsis and infective endocarditis. Embolization is frequently reported with Aerococcus urinae endocarditis (AUE); hence, the presentation is highly variable. Sequelae such as various central nervous system manifestations, sepsis, valvular regurgitation with heart failure and even coronary artery involvement have been reported. We report a case of a 58-year-old man with AUE of the aortic valve, severe aortic regurgitation and embolic stroke as a result of embolization from AUE and ultimately required aortic valve replacement. Our case highlights this rare cause of endocarditis and offers insight into the variability of patient presentation and risk factors to consider.

Application of vascular bundle displacement in the optic disc for glaucoma detection using fundus images.

This paper presents a methodology for glaucoma detection based on measuring displacements of blood vessels within the optic disc (vascular bundle) in human retinal images. The method consists of segmenting the region of the vascular bundle in an optic disc to set a reference point in the temporal side of the cup, determining the position of the centroids of the superior, inferior, and nasal vascular bundle segmented zones located within the segmented region, and calculating the displacement from normal position using the chessboard distance metric. The method was successful in 62 images out of 67, achieving 93.02% sensitivity, 91.66% specificity, and 91.34% global accuracy in pre-diagnosis.

Approaching temporomandibular disorders from a new direction: a randomized controlled clinical trial of the TMDes ear system.

TMDes (Registered Trademark of Ascentia Health, Inc., Rockford, Illinois), custom-fit ear inserts to aid in reducing temporomandibular disorder (TMD) pain, were evaluated in a prospective, three-month, open-label, three-arm, randomized, unblinded clinical trial, which included patients with TMD diagnoses (RDC/TMD) of myofascial pain, arthralgia, and/or disc displacement with reduction; and a screening VAS pain score of > 4. The three treatment groups included: TMDes (n = 60), stabilization splint (n = 64), and jaw exercise regimen (n = 28). The mean change in Craniomandibular Index (CMI) scores (reductions reflecting improvement) from baseline to one month were -27% (TMDes), -20% (stabilization splint), -12% (jaw exercise regimen), and from baseline to three months were -45%, -41%, -36%, reflecting statistically significant noninferiority (p = 0.0096) of the TMDes to the stabilization splint (primary efficacy endpoint). The TMDes produced significant (p < 0.0001) mean changes in VAS pain scores from baseline of -46% at one month and -58% at three months and demonstrated comparable efficacy and safety to the stabilization splint.

Necrotizing fasciitis: a complication of percutaneous coronary revascularization.

Percutaneous coronary revascularization is rarely complicated by infection. Necrotizing fasciitis (NF) is a severe, deep-seated, potentially life-threatening infection of fascia and subcutaneous tissues. We report herein 2 cases of NF in patients undergoing percutaneous transluminal coronary revascularization for treatment of acute coronary syndrome. These are the first 2 reported cases of NF associated with percutaneous coronary revascularization.

Pulmonary artery thrombus and subcapsular liver hematoma in a patient with HELLP syndrome: a therapeutic conundrum.

HELLP syndrome (hemolysis, elevation of liver enzymes, and low platelet count) occurs during pregnancy. Intrahepatic hemorrhage and subcapsular liver hematoma with or without rupture are reported complications of this syndrome. The patient described in this report developed HELLP syndrome associated with a subcapsular liver hematoma and pulmonary artery thrombus, complications that created a therapeutic conundrum.

Disposicion final de los residuos solidos de la ciudad de La Paz

La presente memoria tecnica, comprende un analisis de la problematica ambiental, operacion y descripcion del servicio existente, estudios topograficos, geologicos y de suelos y solucion para la construccion de infraestructuras a ser implementadas, diseño de explotacion y estudios para trabajos de proteccion ambiental, cumpliendo las Normas Bolivianas referente a los Residuos Solidos y el Reglamento de la Ley del Medio Ambiente.

RTU de próstata con agua potable de manantial y kit de baja presión / Prostate RTU with drinkable water of flowing and kit of pressure low

Presentamos la utilización del agua potable de manantial, en la transuretral de próstata, con la creación de un kit de baja presión. Describimos los estudios realizados, que nos llevó a escoger el agua de manantial, para realizar las RTU de próstata (índices de conductividad, electrolitos, PH, bacteriología), el beneficio económico y el diseño de un kit para reseccion con baja presión que incluye punzón. Dilatador, camisa suprapública, canaleta guiadora de sonda. obtenemos una excelente visión, con una buena calidad de corte, sin absorción hídrica, en próstata de diferentes tamaños, con bajos costos operativos. En 250 pacientes procedentes de la Cruz Roja De Valencia y del Centro Clínico de Valencia en el período de mayo de 1996 a mayo de 1997 se han realizado RTU de próstata utilizando agua potable de manantial estéril asociada al kit de baja presión, permitiendose realizar la RTU con una mayor seguridad en la técnica, inclusive en próstatas grandes (100-150 grs) con reducción de los costos operativos

Comparative study of beans from vine and bush type of vegetative growth. Effect of storage on cell wall components as factors in increasing cooking time

Four samples each of black beans representing two types of vegetative growth were collected from farmers' fields in four locationes in Guatemala. Soon after collection, samples were stored at 4 and 38 degrees Celsius at ambient relative humidity and subsamples were withdrawn at 0,45, 90 and 135 days of strage for determination of water absorption, cooking time and analysis of neutral-and acid detergent fiber, cellulose, hemicellulose and lignin. The fiber fraction analysis were done on samples of 0,45 and 90 days of storage. Water absorption for all 4 samples of the bush type was similar at both storage T, however the samples stored at 38 degrees Celsius and at 135 days absorbed more water than when stored at 4 degrees Celsius. The 4 vine types of beans showed different water absorption rates, with two showing patterns similar to those beans of the bush type and two which did absorbed water at a very slow rate. For both types of beans stored at 4 degrees Celsius, cooking time decreased from 0 to 135 days of storage. On the other hand for all bean samples of the two types cooking time increased when stored at 38 degrees Celsius. Analysis of variance showed highly significant effects due to plant type, days of storage, temperature and locality, and for some interactions. Analysis of variance of the fiber fractions showed high significant differences for days of storage for NDF, ADF, cellulose, hemicellulose, and lignin. Plant type gave significant differences for cellulose and hemicellulose. Highly significant differences for hemicellulose were found for the interactions of type x days, type x temperature, locality x type, and type x days x temperature. The rate of synthesis of the 5 fractions were calculated by simple regression analysis. For the bush type of beans some synthesis occurred at 4 degrees Celsius, but it was enhanced when stored at 38 degrees Celsius. For vine type of beans at 4 degrees Celsius relative high rates of synthesis were observed, which were higher at 38 degrees Celsius for NDF, hemicellulose and lignin. Cooking time and fiber fraction contents were subjected to regression analysis. The correlations at 38 degrees Celsius were higher than at 4 degrees Celsius for all fractions for both types of beans, but statistical significance was obtained only for NDF, ADF and cellulose for vince type of beans. These data show therefore that synthesis of cell wall structure fractions, and not only lignin formation, are responsible...

Manejo de la historía clínica por el personal médico y de enfermería de la fundación hospitalaria San Vicente de Paúl. Medellín, Antioquia. 1995 / The use of the clinical records by the medical and nursing staff from th eSan Vicente de Paul hospital fundation.. Medellín-Antioquia 1995

A través de una investigación descriptiva se pretende analizar el manejo de la historia clínica del personal médico y de enfermería de la Fundación Hospitalaria San Vicente de Paúl, con el fin de hacer sugerencias para mejorar los registros clínicos de dicha institución. Se tomó una muestra no probabilística de las historias y una muestra probabilística para el personal que labora en la institución; se escogieron los encuestados de manera aleatoria simple y se encontró que sólo el 13,2 por ciento tiene ordenada la historia clínica; la actualización del plan de cuidados fue diligenciado en un 100 por ciento y no se puede diferenciar entre la nota del personal auxiliar y profesional de enfermería. En cuanto a los conocimientos del personal sobre las normas de manejo de la historia clínica, el 96 por ciento dice conocerlas, el 21,3 por ciento finaliza las notas de evolución con nombre, apellidos y código, el 85,4 por ciento conoce la forma de corregir errores en la historia clínica y el 79,8 por ciento conoce los usos de la historia clínica. Se sugirió: 1) estandarizar el conocimiento del personal sobre el ordenamiento y diligenciamiento correcto de la historia clínica, 2) implementar un programa de vigilancia y control dirigido por el comité de historias clínicas, y 3) fomentar el buen diligenciamiento de las notas del personal por medio de cursos, seminarios y estímulos.

Evaluation of bush and vine black beans for physical, chemical and nutritional characteristics / Estudio comparativo del crecimiento vegetativo de los frijoles de enredo y rastrero. Algunas características físicas, químicas y nutricionales

The present study was undertaken to learn if there are physical, chemical and nutritional differences between vine and bush type of beans. Four samples of black color beans (Phaseolus vulgaris) of the vine type, and four of the bush type were collected from farmers in the same growing area. The samples were analyzad for some physical properties including, 100 seed weight, seze distributions, percent seed coat, water obsorption, cooking time, and of solids on cooking waters. Vine type beans had larger 100-seed weight, larger sized beans, thiker seed coats, and lower of solids in the cooking water than bush type beans. Rate of water absorption was diffeent. The chemical characterization included proximate analysis and fiber fractionation. Vine type beans had, on the average, less ether extract and protein than bush types. No differences were found in fiber fractions, although there was a higher variability in the vine types. Protein quality and protein digestibility when fed as the single protein source, were similar on the average, with more variability in the vine types. Both types, efficiently suppemented maize proteins and the protein digestibility was higher than when fed alone. In general there were no large differences, except in some physical measurements. between vine and bush type beans, with the former showing greater nutritional variability which could be useful in selection programs, if such variability is confirmed.

Ostegénesis imperfecta tipo II en un recién nacido: importancia de su reconocimiento para un asesoramiento genético a los padres / Type II osteogenesis imperfect in newborn : the importance of diagnosis for genetical counseling of the parents

Reportamos el caso de un natimuerto de 36 semanas de edad gestacional nacido en el hospital Nuestra Sra. de la Altagracia de Higuey, el cual presentó Osteogenesis Imperfecta tipo-II. Se señala la importancia de definir el tipo de Osteogénesis, pues los riesgos de recurrencia varian segun la etiologia. La fotografia tomada a este paciente permitio hacer el diagnostico y dar asesoria genetica a sus padres

Síndrome de Histiocitosis: a propósito de un caso

El síndrome de Histiocitosis abarca un espectro de manifestaciones clínicas que van desde la lesión ósea única hasta el severo compromiso cerebral. La imagen anatomopatológica es la de una proliferación de Histiocitos acompañados de otros tipos celulares. Puede remitir espontaneamente. La radioterapia y quimioterapia son de ayuda lo mismo que la cirugía para hacer la limpieza de los bordes oseos afectados. El caso es el de una niña de 2 años con múltiples lesiones óseas, anemia, exoftalmos, retardo en el crecimiento y retardo mental moderados, con dos masas en el cráneo blandas renitentes no dolorosas que, en el acto quirúrgico se observó provenía del hueso y contenía un líquido achocolatado de aspecto cerebroide. No había compromiso meningeo ni parenquimal. Los estudios anatomopatológicos revelaron la presencia de numerosos histiocitos. Dadas las manifestaciones clínicas y la edad de aparición el caso correspondería a un Síndrome intermedio más cercano al Letterer-Siwe por la manifestación visceral. El pronóstico es incierto. La histiocitosis es una Reticulocendoteliosis caracterizada por una proliferación histiocítica de etiología desconocida que abarca un amplio espectro de manifestaciones clínicas que varían desde la lesión aislada y de crecimiento lento hasta una enfermedad agresiva y ampliamente diseminada. Los estudios realizados hasta la fecha han podido demostrar que no es hereditaria ni familiar, que no han sido aislados de las lesiones bacterias hongos ó virus, que no es una enfermedad neoplásica