Anti­CGRP monoclonal antibodies in resistant migraine: preliminary real-world effectiveness and clinical predictors of response at two years.

BACKGROUND: Monoclonal antibodies targeting calcitonin gene-related peptide (anti-CGRP mAbs) have shown clinical effectiveness and safety in randomized clinical studies. However, long-term studies in clinical practice remain limited. AIM: To assess the long-term effectiveness, clinical predictors and safety of three anti-CGRP mAbs (erenumab, galcanezumab, fremanezumab) in resistant migraine patients. METHOD: A single-center retrospective study was conducted from December 2019 to June 2023 involving 120 resistant migraine patients who received at least a month of anti-CGRP mAbs treatment. Patients completed a headache diary that included monthly acute medication intake (MAM), monthly migraine days (MMD), adverse events as well as completed Patient-Reported Outcome questionnaires (MIDAS [Migraine Disability Assessment] and Headache Impact Test 6 [HIT-6]). The number of patients achieving a ≥ 50% reduction in monthly migraine days was determined and classified as ≥ 50% responders, and baseline parameters and logistic regression between responders and non-responders were analyzed to identify potential predictors of response. Adverse events were registered in every follow-up. RESULTS: Treatment with anti-CGRP mAbs led to reductions in MIDAS, HIT-6, MMD and MAM from baseline to 6-24 months. At 6-12 months, responders (61% and 57%, respectively) exhibited lower baseline MMD and MAM. Medication overuse  was associated with non-responders from 6 to 24 months and it was identified as a negative predictor of treatment effectiveness (OR 0.23, 95% CI 0.07-0.74; p = 0.014). CONCLUSION: Anti-CGRP mAbs prove effectiveness and safety over a 24-month period in a RM population. Patients with no medication overuse and lower basal MMDs and MAM may respond better to anti-CGRP mAbs.

Nuclear physics and astronomical observations of compact objects / Física nuclear y observaciones astronómicas de objetos compactos

Abstract We discuss our predictions of two astrophysics observations: neutrino emission and element abundances. We studied the emission and possible detection of neutrinos from past black hole accretion disks. We find neutrinos are copiously emitted from these sites and encourage the development of large facilities for detection. We also studied changes in the synthesis of neutron-rich elements due to the suppression of key nuclear processes. We find important changes in the element abundances due to the, previously overlooked, alpha decay.

Resumen Discutimos nuestras predicciones de dos observaciones astrofísicas: la emisión de neutrinos y las abundancias de elementos. Hemos estudiado la emisión y posible detección de neutrinos emitidos por discos de acreción alrededor de agujeros negros en el pasado. Encontramos que los neutrinos son emitidos en abundancia por discos de acreción y sugerimos el desarrollo de detectores de gran escala para mejorar su detección. También hemos estudiado los cambios en la síntesis de elementos ricos en neutrones, debido a la supresión de procesos nucleares claves. Encontramos que hay cambios importantes en la abundancia de elementos debido al decaimiento alfa.

HDLive ultrasound images of ovarian dermoid cysts: diagnostic accuracy.

OBJECTIVE: To demonstrate that the use of 3D/4D HDLive increases the image quality in the diagnosis of benign cystic ovarian teratomas. MATERIALS AND METHODS: 3D/HDLive ultrasound (US) was used in 31 cases of suspected ovarian cystic teratoma using vaginal 2D US. The following pathognomonic images of mature cystic teratomas were considered for diagnosis: 1) a cystic, unilocular lesion with a densely echogenic tubercle (Rokitansky nodule); 2) a diffuse or partially echogenic mass usually demonstrating sound attenuation; 3) fluid-fluid/fat-fluid levels; 4) dermoid mesh with hyperechogenic calcifications indicating the presence of bone, teeth, or other ectodermally-derived structure; 5) multiple mobile spherical structures (fat globules). RESULTS: Dermoids present a wide spectrum of images depending on the predominant tissue type. In the vast majority of cases there are dense echogenic structures that correspond to complex masses of fatty tissue, sebum, hair, epithelial remnants, along with cartilage or bone. If we catalogue all the images together, the pathognomonic of dermoid are: 1) cystic or solid cystic lesions with a Rokitansky nodule, with bone, teeth or cartilage (six cases, 22.2%); 2) a solid mass with or without attenuation that corresponds with pure sebum (five cases, 18.5%); 3) a diffuse mass with fine bands that correspond with hair inside sebum (four cases, 12.9%) and that may form meshes or plugs corresponding with a mixture of fat, sebum, and hair (three cases, 11.5%). CONCLUSIONS: HDLive U.S. provides some images of exceptional quality that enhance the definition of the structures of these tumors (fat, hair, cartilage, bone, etc.) compared to 2D/3D/4D.

Knee lymphocutaneous fistula secondary to knee arthroplasty.

Lower limb lymphorrhea secondary to a surgical procedure is a rare but difficult-to-solve complication. In lower limb, this entity is frequently associated with vascular procedures around the inguinal area. We report on a case of a knee lymphocutaneous fistula secondary to a knee revision arthroplasty. To our knowledge, no previous reports regarding this complication have been published.

Semi-automatic Sono T measurement of nuchal translucency.

A prospective study of 63 singleton pregnancies between 11 + 0 and 13 + 6 weeks gestation underwent semi-automatic nuchal translucency (NT) measurement and were compared with two-dimensional ultrasonography (2D US). Inter-observer variation and the repeatability were evaluated. Sono T automatically achieves mid-sagittal plane views and measures the maximum NT thickness. Measurements have less inter-observer variation (CI = -0.13, -0.04) when compared with 2D measurements (CI = -0.45, 0.28). It is reproducible and comparable to conventional 2D US technique for NT measurement. However, incorporating Sono T into routine practice requires further program refinements in order to reduce erroneous NT measurements.

Predicting ovarian reserve and reproductive outcome using antimüllerian hormone (AMH) and antral follicle count (AFC) in patients with previous assisted reproduction technique (ART) failure.

PURPOSE OF INVESTIGATION: The main objective of our prospective, observational, analytical research work was to determine whether Anti-Müllerian hormone (AMH) and antral follicle count (AFC) could be effectively used as predictors of ovarian reserve and, possibly, of reproductive outcome with ART. METHODS: We studied 143 IVF/ET cycles in patients with a previous history of ART failure, all of them supposed to be of poor prognosis, who had agreed to another ART attempt after knowing their AMH, AFC, and base hormone (FSH, LH, 17 beta-estradiol) levels. RESULTS: AMH and AFC showed a positive correlation with the number of oocytes retrieved (p = 0.0016) and (p < 0.0001), respectively and with percentage of MII oocytes, (p = 0.00756) and (p < 0.001). The combined use of these markers showed an area under the curve of 82.2% for oocytes retrieved. Our results shows a very high cancelation (22% of started cycles) and very low pregnancy rates (6.7% and 9.8%) in low and normoresponders, respectively. CONCLUSIONS: AMH levels and AFC are reliable indicators of ovarian reserve. Patients with ovarian reserve levels that predict a very low probability of success should be informed that the poor prognosis associated with these values may not justify the expense of IVF/ET.

Activation of nuclear factor-kappa B signalling promotes cellular senescence.

Cellular senescence is a programme of irreversible cell cycle arrest that normal cells undergo in response to progressive shortening of telomeres, changes in telomeric structure, oncogene activation or oxidative stress. The underlying signalling pathways, of major clinicopathological relevance, are unknown. We combined genome-wide expression profiling with genetic complementation to identify genes that are differentially expressed when conditionally immortalised human fibroblasts undergo senescence upon activation of the p16-pRB and p53-p21 tumour suppressor pathways. This identified 816 up and 961 downregulated genes whose expression was reversed when senescence was bypassed. Overlay of this data set with the meta-signatures of genes upregulated in cancer showed that nearly 50% of them were downregulated upon senescence showing that even though overcoming senescence may only be one of the events required for malignant transformation, nearly half of the genes upregulated in cancer are related to it. Moreover 65 of the up and 26 of the downregulated genes are known downstream targets of nuclear factor (NF)-κB suggesting that senescence was associated with activation of the NF-κB pathway. Direct perturbation of this pathway bypasses growth arrest indicating that activation of NF-κB signalling has a causal role in promoting senescence.

Bioinformatics construction of the human cell surfaceome.

Cell surface proteins are excellent targets for diagnostic and therapeutic interventions. By using bioinformatics tools, we generated a catalog of 3,702 transmembrane proteins located at the surface of human cells (human cell surfaceome). We explored the genetic diversity of the human cell surfaceome at different levels, including the distribution of polymorphisms, conservation among eukaryotic species, and patterns of gene expression. By integrating expression information from a variety of sources, we were able to identify surfaceome genes with a restricted expression in normal tissues and/or differential expression in tumors, important characteristics for putative tumor targets. A high-throughput and efficient quantitative real-time PCR approach was used to validate 593 surfaceome genes selected on the basis of their expression pattern in normal and tumor samples. A number of candidates were identified as potential diagnostic and therapeutic targets for colorectal tumors and glioblastoma. Several candidate genes were also identified as coding for cell surface cancer/testis antigens. The human cell surfaceome will serve as a reference for further studies aimed at characterizing tumor targets at the surface of human cells.

Thermal conductivity and phase separation of the crust of accreting neutron stars.

Recently, crust cooling times have been measured for neutron stars after extended outbursts. These observations are very sensitive to the thermal conductivity kappa of the crust and strongly suggest that kappa is large. We perform molecular dynamics simulations of the structure of the crust of an accreting neutron star using a complex composition that includes many impurities. The composition comes from simulations of rapid proton capture nucleosynthesis followed by electron captures. We find that the thermal conductivity is reduced by impurity scattering. In addition, we find phase separation. Some impurities with low atomic number Z are concentrated in a subregion of the simulation volume. For our composition, the solid crust must separate into regions of different compositions. This could lead to an asymmetric star with a quadrupole deformation. Observations of crust cooling can constrain impurity concentrations.

Nonlinear optical waveguides generated in lithium niobate by swift-ion irradiation at ultralow fluences.

A novel method to produce optical waveguides is demonstrated for lithium niobate (LiNbO(3)). It is based on electronic excitation damage by swift ions, i.e., with energies at approximately 1 MeV/amu or above. The new technique uses high-energy medium-mass ions, such as Cl, with electronic stopping powers above the threshold value for amorphization (5-6 keV/nm), reaching the maximum value a few micrometers inside the crystal. At the ultralow fluence regime (10(12)-10(13) cm(-2)) an effective nanostructured medium is obtained that behaves as an optical waveguide where light propagates transversally to the amorphous nanotracks created by every single impact. The method implies a reduction of 4 orders of magnitude with respect to He implantation. The optical waveguides present reasonable losses (~10 dB/cm) and significant second-harmonic generation (SHG) and electro-optic (EO) responses (>50% bulk) for the lowest fluences.

Gene expression profiling of clinical stages II and III breast cancer.

Clinical stage (CS) is an established indicator of breast cancer outcome. In the present study, a cDNA microarray platform containing 692 genes was used to identify molecular differences between CSII and CSIII disease. Tumor samples were collected from patients with CSII or CSIII breast cancer, and normal breast tissue was collected from women without invasive cancer. Seventy-eight genes were deregulated in CSIII tumors and 22 in CSII tumors when compared to normal tissue, and 20 of them were differentially expressed in both CSII and CSIII tumors. In addition, 58 genes were specifically altered in CSIII and expression of 6 of them was tested by real time RT-PCR in another cohort of patients with CSII or CSIII breast cancer and in women without cancer. Among these genes, MAX, KRT15 and S100A14, but not APOBEC3G or KRT19, were differentially expressed on both CSIII and CSII tumors as compared to normal tissue. Increased HMOX1 levels were detected only in CSIII tumors and may represent a molecular marker of this stage. A clear difference in gene expression pattern occurs at the normal-to-cancer transition; however, most of the differentially expressed genes are deregulated in tumors of both CS (II and III) compared to normal breast tissue.

Gene expression profiling of clinical stages II and III breast cancer

Clinical stage (CS) is an established indicator of breast cancer outcome. In the present study, a cDNA microarray platform containing 692 genes was used to identify molecular differences between CSII and CSIII disease. Tumor samples were collected from patients with CSII or CSIII breast cancer, and normal breast tissue was collected from women without invasive cancer. Seventy-eight genes were deregulated in CSIII tumors and 22 in CSII tumors when compared to normal tissue, and 20 of them were differentially expressed in both CSII and CSIII tumors. In addition, 58 genes were specifically altered in CSIII and expression of 6 of them was tested by real time RT-PCR in another cohort of patients with CSII or CSIII breast cancer and in women without cancer. Among these genes, MAX, KRT15 and S100A14, but not APOBEC3G or KRT19, were differentially expressed on both CSIII and CSII tumors as compared to normal tissue. Increased HMOX1 levels were detected only in CSIII tumors and may represent a molecular marker of this stage. A clear difference in gene expression pattern occurs at the normal-to-cancer transition; however, most of the differentially expressed genes are deregulated in tumors of both CS (II and III) compared to normal breast tissue.

Estudio de validación de la linfogammagrafía y biopsia del ganglio centinela en cáncer de mama / Validation study of the lymphadenectomy and sentinel node biopsy in the breast cancer

Objetivo: La afectación de los ganglios axilares constituyeel principal factor pronóstico en cáncer de mama en cuantosupervivencia global. El propósito de este trabajo es el de presentarlos resultados de la primera fase de realización de labiopsia del ganglio centinela en cáncer de mama en nuestrocentro.Métodos: Se incluyó un total de 50 pacientes a las que serealizó la biopsia del ganglio centinela, seguida de linfadenectomíade los niveles I y II. Las indicaciones fueron tumor inferiora 2,5 cm de diámetro sin sospecha de afectación axilar,pacientes con carcinoma ductal in situ extenso y sin quimioterapiaprevia.Resultados: La tasa de detección general fue del 98%.Hubo un falso negativo. Se encontraron micrometástasis entres pacientes.Conclusión: La biopsia del ganglio centinela es un métodofiable para determinar el estado de los ganglios linfáticosregionales en pacientes con cáncer de mama

Objective: The status of the axilla is the single most importantprognostic indicator of overall survival in patients withbreast cancer. The aim of this study was to validate sentinelnode biopsy for axillary staging after the initial learning phase.Methods: A total of 50 patients, who had standard sentinelnode biopsy followed by level I and II axillary clearance,were recruited prospectively. Accepted indications were tumorless than 2,5 cm without suspicious findings in the axilla, patientswith large ductal carcinoma in situ and patients withoutpreoperative chemotherapy.Results: The overall detection rate was 98 per cent. Therewas one false negative. Micrometastases were found in threepatients.Conclusion: The sentinel node biopsy is a reliable methodfor determining the status of the regional lymph nodes in patientswith breast cancer

Relationship of the methylenetetrahydrofolate reductase C677T polymorphism with microsatellite instability and promoter hypermethylation in sporadic colorectal cancer

The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is associated with the expression of a thermolabile enzyme with decreased activity that influences the pool of methyl-donor molecules. Several studies have reported an association between C677T polymorphism and susceptibility to colorectal cancer (CRC). Considering that methylation abnormalities appear to be important for the pathogenesis of CRC, we examined the correlation between the genotype of the MTHFR C677T polymorphism, hypermethylation of the promoter region of five relevant genes (DAPK, MGMT, hMLH1, p16(INK4a), and p14(ARF)), and microsatellite instability, in 106 patients with primary CRCs in Brazil. We did not find significant differences in the genotypic frequencies of the MTHFR C677T polymorphism when one or more loci were hypermethylated. However, we did find a significant excess of 677TT individuals among patients with CRC who had microsatellite instability. This strong association was independent of the methylation status of hMLH1 and of the biogeographical genomic ancestry of the patients. Although the mechanism responsible for the link between the C677T polymorphism and microsatellite instability was not apparent, this finding may provide a clue towards a better understanding of the pathogenesis of microsatellite instability in human colorectal cancer.

Utilidad del SPECT cerebral en el diagnóstico de la encefalopatía de Wernicke-Korsakoff / Use of brain SPECT imaging in the diagnosis of Wernicke-Korsakoff´s encephalopathy

No disponible

No disponible

Association of CYP3A4 genotype with detection of Vy/JB trans-rearrangements in the peripheral blood leukocytes of pediatric cancer patients undergoing chemotherapy for all

Cancer patients receiving chemotherapy are exposed to high doses of cytotoxic and genotoxic drugs which, in some cases, can lead to treatment related leukemia. Since this only occurs in a minority of patients, however, it is possible some individuals are predisposed due to genetic polymorphisms in genes for enzymes that mediate drug metabolism. To address this possibility we measured the genotoxicity of chemotherapeutic agents in patients receiving treatment for ALL by the frequency of the Vã/Jâ trans-rearrangement in their peripheral blood leukocytes and compared this with CYP3A4 genotype. CYP3A4 is the most abundant of the cytochrome P450 (CYP) enzyme in the liver and intestine which contains a common −392A>G substitution in the promoter region (CYP3A4*1B allele). We found a significant increase in the frequency of rearrangements during chemotherapy only in patients homozygous for the wild type CYP3A4*1A allele. This provides a direct link between CYP3A4 genotype and susceptibility to drug genotoxicity thus strengthening the possibility that predisposition to treatment related leukemia may be measurable by simple genetic testing.