How we approach the treatment of patients with high-risk neuroblastoma with naxitamab: experience from the Hospital Sant Joan de Déu in Barcelona, Spain.

Naxitamab [humanized 3f8 (hu3F8)] is a humanized monoclonal antibody (mAb) targeting the disialoganglioside GD2. It was approved in 2020 by the United States Food and Drug Administration (FDA) in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) for treatment of pediatric and adult patients with relapsed/refractory high-risk neuroblastoma, limited to the bone or bone marrow (BM). The team at Sant Joan de Déu Children's Hospital in Barcelona, Spain, have been using naxitamab to treat neuroblastoma under clinical trial protocols [e.g. Trial 201, and hu3F8, irinotecan, temozolomide, and sargramostim (GM-CSF) (HITS) study] and compassionate use since 2017. The team has experience with two primary regimens: naxitamab with GM-CSF only, or naxitamab in combination with irinotecan, temozolomide, and GM-CSF (chemoimmunotherapy). This article aims to provide a practical overview of the team's experience with naxitamab to date, including preparing the treatment room and selecting the team. Adverse event management, including the use of ketamine to manage pain during anti-GD2 mAb infusions, is also discussed. We hope this will provide practical information for other health care providers considering offering this treatment.

[The methodology of calculation of indices of provision of population with beds of palliative medical care].

The enhancement of organization of palliative medical care to increase life quality of terminally ill patients is one of directions of development of health care system. To elaborate measures of improving accessibility and quality of palliative medical care, it is necessary to apply single unified methodology of calculating indices and criteria. One of them is provision of bed capacity. The purpose of the study is to elaborate methodology of calculating control indices of provision population with beds to render palliative medical care. The indices are calculated on the basis of statistical processing of monitoring corresponding data in the subjects of the Russian Federation.

Noncoding RNAs as potential biomarkers for DIPG diagnosis and prognosis: XIST and XIST-210 involvement.

PURPOSE: Diffuse intrinsic pontine gliomas (DIPGs) are the most fatal primary brainstem tumors in pediatric patients. The identification of new molecular features, mediating their formation and progression, as non-coding RNAs (ncRNAs), would be of great importance for the development of effective treatments. METHODS: We analyzed the DIPGs transcriptome with the HTA2.0 array and it was compared with pediatric non-brainstem astrocytoma expression profiles (GSE72269). RESULTS: More than 50% of the differentially expressed transcripts were ncRNAs and based on this, we proposed a DIPGs ncRNA signature. LncRNAs XIST and XIST-210, and the HBII-52 and HBII-85 snoRNA clusters were markedly downregulated in DIPGs. qPCR assays demonstrated XIST downregulation in all non-brainstem astrocytomas, in a gender, age, and brain location-independent manner, as well as in DIPGs affecting boys; however, DIPGs affecting girls showed both downregulation and upregulation of XIST. Girls' with longer survival positively correlated with XIST expression. CONCLUSIONS: The involvement of ncRNAs in DIPGs is imminent and their expression profile is useful to differentiate them from non-neoplastic tissues and non-brain stem astrocytomas, which suggests their potential use as DIPG biomarkers. In fact, XIST and XIST-210 are potential DIPG prognostic biomarkers.

Factors associated with infection of primary total knee prosthesis in older adults in a referral hospital in Peru. 2012-2015. / Factores asociados a infección de prótesis total de rodilla primaria en adultos mayores en un hospital de referencia en Perú. 2012-2015.

OBJECTIVE: To determine the risk factors associated with prosthetic knee infection in elderly patients in a referral hospital in Peru. PATIENTS AND METHODS: A case and control study was performed. The calculated sample was 44 cases and 132 controls. The data were collected retrospectively from clinical records. U-Mann Whitney and Chi-square tests were performed in the comparison of cases and controls. Odds ratios (OR) were calculated in a binary logistic regression analysis to identify the risk factors, a P<.05 and a 95% confidence interval (CI) were considered significant. RESULTS: Significant (P<.05) risk factors evidenced in the bivariate analysis were obesity (OR=9.72; 95%CI: 4.47-21.14), smoking (OR=4.06; 95%CI: 1.59-10.39), rheumatoid arthritis (OR=4.66; 95%CI: 1.52-14.32), diabetes mellitus type2 (OR=5.63; 95%CI: 2.69-11.78), persistent drainage (OR=9.27; 95%CI: 3.85-22.31), superficial infection (OR=6.87; 95%CI: 3.25-14.49) and prolonged hospital stay (OR=4.67; 95%CI: 2.26-9.64). In the multivariate analysis where it was adjusted for confounding variables, it was determined that risk factors were obesity (ORa=9.14; 95%CI: 3.28-25.48), diabetes mellitus (ORa=3.77; 95%CI: 1.38-10.32), persistent drainage (ORa=4.64; 95%CI: 1.03-20.80) and superficial wound infection (ORa=27.35; 95%CI: 2.57-290.64). CONCLUSIONS: Risk factors for prosthetic knee infection identified in this study are preventable. The main risk factors were obesity, diabetes mellitus type2, superficial wound infection and persistent drainage, which were considered together or separately to be risk factors in the population studied.

Prospective comparison among three intrarectal anesthetic treatments combined with periprostatic nerve block during transrectal ultrasonography-guided prostate biopsy.

BACKGROUND: Recent trends in prostate biopsy analgesia suggest a combination anesthetic to provide better pain relief than periprostatic nerve block (PPNB) alone. This study aimed to demonstrate the efficacy and safety of three intrarectal local anesthesia (IRLA) combined with PPNB in patients undergoing transrectal ultrasonography (TRUS)-guided prostate biopsy. METHODS: In this prospective, randomized study, 120 prostate biopsy patients were equally divided into four IRLA groups: group 1 (placebo) received simple lubrication; group 2 received 2% lidocaine gel; group 3 received 100 mg indomethacin suppository and group 4 received 5% prilocaine/lidocaine (EMLA) cream. PPNB with 2% lidocaine was applied in all groups. A ten-point visual analog scale evaluated both pain associated with the probe insertion and pain associated with prostate sampling. Adverse effects or complications due to anesthesia during and after the procedure were documented. RESULTS: Compared with group 1, groups 3 and 4 had significantly lower pain scores at both probe insertion and prostate sampling while group 2 showed no significant differences at both pain scores. Moreover, group 4 showed significantly lower pain scores at probe insertion compared to group 3, while no significant difference was observed at prostate sampling. Mild complications were observed in all groups with no significant difference in the incidence of complications between groups. CONCLUSION: Intrarectal application of EMLA cream is a more efficient pain reduction than either 2% lidocaine gel or 100 mg indomethacin suppository when applied combined with PPNB. This combination represents an effective option of pain relief for patients undergoing TRUS-guided prostate biopsy.

Chemical composition and physicochemical properties of Phaeodactylum tricornutum microalgal residual biomass.

The production of photosynthetic biofuels using microalgae is a promising strategy to combat the use of non-renewable energy sources. The microalgae residual biomass is a waste by-product of biofuel production; however, it could prove to have utility in the development of sustainable nutraceuticals and functional foods. In this study, a comprehensive characterisation of the under-utilised Phaeodactylum tricornutum microalgae residual biomass is presented. Proximal composition, antioxidant capacity (using three different antioxidant assays; oxygen radical absorbance capacity; radical cation activity, ABTS; and radical scavenging activity, DPPH), and total phenolic content of free and bound polyphenols were determined. Additionally, the physicochemical properties of water activity, pH, water absorption index, water solubility index, and dispersibility were evaluated. Results revealed that P. tricornutum microalgae residual biomass exhibits a relatively high protein and carbohydrate content, with values of 36.67% and 46.78%, respectively; and most carbohydrates were found as total dietary fibre (45.57%), of which insoluble dietary fibre was the most predominant (43.54%). Antioxidant capacity values for total phytochemicals of 106.22, 67.93, 9.54 µM TE g-1 dw were determined by oxygen radical absorbance capacity, ABTS, and DPPH assays, respectively. Total phenolic content was found to be 2.90 mg GAE g-1 dw. Interestingly, antioxidant capacity and total phenolic content were higher in bound than in free phytochemical extracts. The physicochemical analysis showed P. tricornutum microalgae residual biomass to have suitable properties for the generation of a beverage with Aw, pH, water absorption index, water solubility index, and dispersibility values of 0.45, 7.12, 3.40 g gel g-1 dw, 2.5 g solids 100 g-1 dw, and 90%, respectively. Hence, P. tricornutum microalgae residual biomass could be considered a potential source of bioactive compounds suitable for the production of functional food exhibiting antioxidant capacity and high dietary fibre content.

Imágenes de fluorescencia de rayos X en huesos humanos y su potencial aplicación in vivo / Images of X-ray fluorescence in human bones and their potential application in vivo

El conocimiento de la concentración y la distribución espacial de los elementos químicos presentes en diferentes órganos y tejidos resulta un parámetro útil para el diagnóstico de determinadas patologías o niveles por sobre los límites tolerables, por lo tanto el conocimiento de los elementos presentes en un tejido vivo, su concentración y distribución espacial podría proporcionar información relevante respecto del estado de salud de un individuo. Se presenta una aplicación de una nueva técnica de fluorescencia rayos X dispersiva en energía mediante barrido, la cual se puede aplicar a muestras de diferente composición y forma, a diferencia de, la mayoría de las técnicas existentes, que son aplicables sólo a muestras planas. Esta técnica permite la obtención de imágenes bidimensionales de los elementos químicos presentes en las muestras de un modo tanto mono como multielemental. En este trabajo es aplicada a un conjunto muestras óseas humanas y tarso y dedos de Gallus gallus (pollo) faenado, obteniéndose una distribución espacial 2D con diferentes niveles de intensidad fluorescente dependiendo del elemento detectado y de su concentración. Las imágenes logradas consideran áreas de hasta104 mm2, con una resolución espacial de hasta 0,25 mm2 y en un tiempo de adquisición de alrededor de 20 min. También se lleva a cabo un cálculo de la dosis de la radiación asociada a este tipo de análisis XRF, encontrándose que los niveles aplicados para la obtención de una imagen XRF son tolerables. Lo anterior permite concluir que sería posible el uso de esta técnica para una aplicación in vivo.

The knowledge of the concentration and spatial distribution that chemical elements present in different organs and tissues is a useful parameter for diagnosis of certain diseases or element levels above limits accepted as healthy. Therefore, development of techniques to identify the chemical elements present in a living tissue and obtaining information about their concentration and spatial distribution might be relevant to determine an individual's health status. This work presents an application of a new X-ray fluorescence technique, energy dispersive by scanning, which can be applied to samples of different composition and shape, unlike most of the existing techniques, only applicable to flat samples. This technique allows the acquisition of two-dimensional images of the chemical elements present in a sample in both mono and multi-elemental mode. In this work the technique is applied to a set of human bone samples and tarsus and fingers of a dead Gallus gallus (chicken), obtaining a 2D spatial distribution with different levels of fluorescence intensity, depending on the detected element and its concentration. The acquired images consider areas up to 104 mm2, with a spatial resolution of 400 mm2 and an acquisition time of about 20 min. Calculations of the radiation dose associated with this type of XRF analysis were also carried out, and the findings show that the levels applied to obtain an XRF image are tolerable. The latter leads to the conclusion that it would be possible to use this technique for an in vivo application.

[Urethroplasty with dorsal oral mucosa graft in female urethral stenosis]. / Uretroplastia con injerto dorsal de mucosa oral en estenosis uretral femenina.

INTRODUCTION: Female urethral stenosis is not a very common pathology and its treatment is controversial. Therapeutic options vary from urethral dilatation and internal urethrotomy to other more complex reconstructive surgical techniques. The use of oral mucosa grafts to treat urethral stenosis has provided excellent long-term results in men, however there are few studies on their use in female urethral stenosis. We present our experience in the management of urethral stenosis using dorsal oral mucosa grafting. MATERIALS AND METHODS: We present 2 cases of female patients with a history of repeated urinary tract infections associated with low obstructive uropathy. In both cases, we encountered distal urethral stenosis, where both were treated with urethral plasty by means of dorsal oral mucosa grafting. RESULTS: The surgery took place without complications. Hospitalization time was 24 hours in both cases. The catheter was removed on the tenth postoperative day. The urethrocystography showed good urethral calibre with no signs of urinary fistula. After a mean follow-up of 18 months, neither patient presented symptoms of low obstructive uropathy or urinary incontinence. CONCLUSIONS: Urethroplasty with dorsal oral mucosa grafting is a reproducible and effective therapeutic option for the treatment of urethral stenosis in women.

[Cys-loop ligand-gated ion channels modulation by protein kinases A and C]. / Modulacion de los receptores ionotropicos de tipo cys-loop por proteincinasas A y C.

INTRODUCTION: In the nervous system, rapid chemical neurotransmission is mediated by ionotropic receptors that are activated by ligand binding. Ligand binding to its receptor promotes the selective flow of ions into the cell which changes the electrical potential of the cell membrane. Cys-loop type receptors belong to the ligand-gated ion channel superfamily including the nicotinic acetylcholine receptor, the gamma-aminobutyric acid, glycine, serotonin and zinc. Several studies showed that the activity of these receptors was modified in response to protein kinases A and C activation; the different results, apparently contradictory, could be explained by the involvement of several factors such as the type of subunits that make up these receptors, components of the cytoskeleton and sub-types of kinases and phosphatases present in nerve tissue studied. AIM: To review the effect of protein kinases A and C on the activity of cys-loop receptors. DEVELOPMENT: In this review we describe experiments conducted in different regions where it was determined the effect of these kinases on the function of neurotransmitter receptors mostly distributed in the nervous system. CONCLUSIONS: The cys-loop receptors regulation by protein kinases occurs through the activation of other receptors (cross-talk) that are expressed at different stages of development and nervous system areas.

Increased expression of AML1-a and acquired chromosomal abnormalities in childhood acute lymphoblastic leukemia.

A semi-quantitative expression analysis of both AML1-a and AML1-total was performed by RT-PCR in 19 children with acute lymphoblastic leukemia (ALL) at diagnosis. AML1-a expression was assessed in 16 bone marrow (BM) and 13 peripheral blood (PB) samples whereas AML1-total was assessed in 17 BM and 16 PB samples. These analyses were also carried out in 15 PB samples of healthy controls. In addition, 18/19 patients were karyotyped: 11 had an unmodified constitutional karyotype (CK) and seven exhibited acquired chromosomal abnormalities (ACA). The expression of AML1-a was significantly increased in BM and PB when compared with the controls (p < 0.013 and p < 0.035, respectively). A significant increase was found in the expression of AML1-a in BM of the ACA group compared with the CK group (p < 0.0009). The expression of AML1-a in BM and PB showed a significant increase in the ACA group compared with controls (p < 0.00001 and p < 0.012, respectively); in contrast, the CK group did not differ from the controls. These observations may mean that the increase of AML1-a favours the progression of leukemia.

Detection and monitoring of clonality in peripheral blood and bone marrow of patients with B-cell lymphoproliferative disorders.

Bone marrow (BM) is accepted as the tissue of choice for the detection of monoclonal populations in leukemias and lymphomas; however, obtaining BM can be painful and traumatic for the patients. Although it is possible to detect clonality in peripheral blood (PB) samples, there are no reports comparing the results observed from BM with those from PB. Lymphoblastic leukemias and lymphomas are derived from B-lymphocytes in 80% of cases. In the early stages of their maturation, the immunoglobulin heavy chain genes (IgH) undergo rearrangements among their V, D, and J segments, giving rise to the Complementarity Determining Regions (CDR). Of these, CDR3 is unique for each lymphocyte and therefore it can be used as a tumour-specific marker in these malignant disorders. Among the 104 patients from whom we obtained pre-treatment paired samples of PB and BM, 94 (90.4%) showed concordant results. Similarly, at the end of treatment, 40 of 44 patients (90.9%) showed this concordance. During treatment only 24 patients were monitored and monoclones disappeared in 12 patients; in the other half, they persisted either partial or totally. We demonstrate that the detection and monitoring of monoclonal populations in the PB, in comparison with BM, was achieved with a statistical sensitivity of 90% and specificity of 92%.

Paternal isodisomy 7q secondary to monosomy 7 at recurrence in a Down syndrome child with acute myelogenous leukemia.

We report a boy with Down syndrome and leukemia who acquired uniparental isodisomy of chromosome 7q as a secondary chromosomal change during recurrence of the disease. His karyotype before therapy was 46,XY,der(1)t(1;1)(p36;q32),-7,+21c/46,idem,del(9)(p22), whereas at recurrence it was 46,XY,der(1)t(1;1)(p36;q32,-7,der(7)(qter-->p22 through pter::q10-->qter),del(9)(p22),+21c/47,XY,+21c. By using polymerase chain reaction amplification of D7S493 and D7S527 markers, we identified the loss of the maternal chromosome 7 with a consequent paternal isodisomy in the clone with dup7q. This rearrangement could be implicated in the progression of the disease by causing (1) nullisomy for a gene or genes located on 7p22-->pter, (2) functional double doses of exclusively paternal expressed genes, and (3) restoration of the effects produced by haploinsufficiency of biparental expressed genes.

[Oocyte maturation and its relation to various components of the follicular fluid]. / Maduración del ovocito y su relación con algunos componentes del líquido folicular.

Thirty five follicular fluid (FF) non hematic samples were analyzed. It were obtained from patients who receive ovulation induction for in vitro fertilization (FIV) and gamete intrafallopian tube transfer (GIFT). The purpose of this retrospective study was to localize one or more markers for the oocyte maturity. The degree of expansion of the oocyte-cumulus-corona radiata complex (COCC), was measured and correlated with the absorbance of the yellow pigment from FF. The scanning spectrophotometry was made in the visible range at 350 to 600 nm. The total amount of protein, estradiol and progesterone were correlated too. Spectrophotometric scan showed four groups: the first one with 20 samples had'n one peak at 413.8 nm. The 45% of this ova were classified as immature by the morphology of the COCC. The second group with seven samples showed one peak at 457.2 nm. All of this oocytes were previously classified as preovulatories. In the next two groups the combination of two peaks were present. The group three with one peak at 416.4 nm and other at 457.9 nm; with one oocyte atretic and two immature. The group four with five samples that showed the first peak at 413.6 nm, and the second peak at 562 nm of maximum absorbance. Two of this ova were classified as atretic and the rest of them like preovulatories. In this study we could not find correlation between the proteins, estradiol and progesterone levels with the morphology of the COCC. In conclusion, spectrophotometric scan of the FF could be of great value for scoring the oocyte mature, mainly in the GIFT.

Evaluación de un programa de pesquisa de hipoacusia en recien nacidos / Evaluation of the program of research on hypoacusia in newborn infants

Un equipo multidisciplinario desarrolló el Programa de Pesquisa de Niños Sordos (PROPENSO) en dos maternidades de la ciudad de Buenos Aires, una pública, R. Sardá (RS) y la otra privada del Sanatorio Otamendi y Miroli (SOM). El tamizado sistemático de 5489 recién nacidos desde mayo a diciembre de 1984 reveló 267 (4,8 por ciento) que reunían factores de "alto riesgo" para hipoacusia. La evaluación diagnóstica posterior, realizada en su mayoría en el centro del CEIDHI se completó en 155 (58 por ciento) niños de la cohorte de riesgo: 112 (52,6 por ciento) de los 213 pesquisados en RS y 43 (79,6 por ciento) de los 54 del SOM. En esta etapa se analizó la validez de una prueba subjetiva (audiometría conductual) en relación a un barrido de alta intensidad con potenciales evocados audiométricos de tronco (PEAT) observando una sensibilidad de 46 por ciento y una especificidad de 94 por ciento. Se detectaron finalmente 4 lactantes con hipoacusia severa bilateral persistente y 5 con sordera unilateral y se inició en ellos tempranamente la orientación y tratamiento. Debe contemplarse, para mejorar la eficiencia de futuras estrategias de pesquisa de hipoacusia infantil, que: a) el uso de un listado para identificar factores de riesgo en recién nacidos es un procedimiento efectivo, b) es difícil lograr el seguimiento ambulatorio, especialmente para familias de bajos ingresos, y c) la audiometría conductal parece ser un método suficientemente confiable para el reconocimiento inicial de hipoacusia severa (pero no en los primeros meses de vida).

Capacidad reductora del espermatozoide humano normal sobre el NBT (nitroazul de tetrazolio). / Reduction capacity on nitroblue tetrazolium (NBT) of the normal human spermatozoa

Se determinaron las condiciones experimentales para juzgar si los espermatozoides lavados de varones sanos y fecundos tienen la capacidad de reducir el nitroazul de tetrazolio (NBT) de manera semejante (aunque en ausencia de algun substrato) a como lo hacen los leucocitos. La produccion del color azul de formazan obtenido sugiere la participacion de la enzima mitocondrial oxidoreductasa del NADH.Esta capacidad del espermatozoide hacia la reduccion del NBT podria tomarse como un reflejo de la capacidad metabolica del espermatozoide humano. Nuestros resultados parecen utiles para comparar la capacidad reductora (metabolica) de los espermatozoides normales con la de los obtenidos de sujetos que cursan con problemas de fecundidad