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1.
Reprod Biol Endocrinol ; 22(1): 34, 2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38532462

RESUMEN

BACKGROUND: Pregnancy-associated breast cancer (PABC) is a rare entity whose prognosis has previously been studied and is subject to controversy. METHODS: Survival of patients with PABC diagnosed between 2009 and 2021 with breast cancer during pregnancy or until 1 year after childbirth was compared with non-pregnant patients with breast cancer from the same period at La Paz University Hospital. Cox proportional hazards regression was used to compare disease-free (DFS) and overall (OS) survival between the groups, adjusting for grade and pathologic stage. RESULTS: Among the 89 included patients with breast cancer, 34 were diagnosed during pregnancy, and 55 were not pregnant. The pregnant patients were more likely to have grade 3 tumors (61.3% vs 37%, p = 0.023) and an advanced stage (pathologic stage III-IV: 44.1% vs 17.6%, p = 0.008). Median follow-up was 47 months for the pregnant group and 46 months for the control group. After adjustments for tumor grade and pathologic stage, OS was comparable between the groups (HR 2.03; 95% CI 0.61 to 6.79; P = 0.25). CONCLUSIONS: The outcome of women diagnosed with PABC is comparable to young non-pregnant controls. However, it should be taken into account that PABC has a more aggressive phenotype.


Asunto(s)
Azidas , Neoplasias de la Mama , Complicaciones Neoplásicas del Embarazo , Propanolaminas , Humanos , Embarazo , Femenino , Neoplasias de la Mama/patología , Pronóstico , Parto
2.
Int Arch Allergy Immunol ; : 1-11, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38830344

RESUMEN

BACKGROUND: Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is the most frequent medication to be involved in hypersensitivity drug reactions (HDRs). Other analgesic/anti-inflammatory drugs in the arylpropionic group are also relevant, albeit to a lesser extent. Ibuprofen is widely consumed by people of all ages, both on medical prescription and over the counter; moreover, it is an organic contaminant of surface waters and foods. While numerous drugs cause HDR, ibuprofen's underlying mechanisms are more intricate and involve both specific immunological and non-immunological mediated reactions. SUMMARY: we concentrate on immediate responses, including urticaria with or without angioedema, anaphylaxis, and angioedema, classifying reactions according to whether they are caused by single or multiple NSAIDs and based on the mechanisms at play. Both groups may experience anaphylaxis, defined as an immediate, severe systemic reaction involving at least two organs, though the frequency and severity can vary. Following this classification, more clinical manifestations can be identified. Diagnosis is partly based on a detailed clinical history, including information about ibuprofen and/or other arylpropionic derivatives involved, the interval between drug intake and symptoms onset, clinical manifestations, number of episodes, and the patient's tolerance or response to other medications - mainly non-chemically related NSAID - both before and after reactions to ibuprofen and/or other arylpropionic drugs. A drug provocation test is frequently necessary to make a diagnosis. KEY MESSAGE: Because ibuprofen is the most widely prescribed NSAID, it is reasonable to assume its role as the leading cause of HDR will only become more important.

3.
Pharmacol Res ; 200: 107061, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38199278

RESUMEN

The development of Pharmacogenetics and Pharmacogenomics in Western Europe is highly relevant in the worldwide scenario. Despite the usually low institutional support, many research groups, composed of basic and clinical researchers, have been actively working for decades in this field. Their contributions made an international impact and paved the way for further studies and pharmacogenomics implementation in clinical practice. In this manuscript, that makes part of the Special Issue entitled Spanish Pharmacology, we present an analysis of the state of the art of Pharmacogenetics and Pharmacogenomics research in Europe, we compare it with the developments in Spain, and we summarize the most salient contributions since 1988 to the present, as well as recent developments in the clinical application of pharmacogenomics knowledge. Finally, we present some considerations on how we could improve translation to clinical practice in this specific scenario.


Asunto(s)
Farmacogenética , Medicina de Precisión , Europa (Continente)
4.
Int J Mol Sci ; 25(12)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38927996

RESUMEN

The pathogenesis of multiple sclerosis (MS) is not completely understood, but genetic factors, autoimmunity, inflammation, demyelination, and neurodegeneration seem to play a significant role. Data from analyses of central nervous system autopsy material from patients diagnosed with multiple sclerosis, as well as from studies in the main experimental model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), suggest the possibility of a role of oxidative stress as well. In this narrative review, we summarize the main data from studies reported on oxidative stress markers in patients diagnosed with MS and in experimental models of MS (mainly EAE), and case-control association studies on the possible association of candidate genes related to oxidative stress with risk for MS. Most studies have shown an increase in markers of oxidative stress, a decrease in antioxidant substances, or both, with cerebrospinal fluid and serum/plasma malonyl-dialdehyde being the most reliable markers. This topic requires further prospective, multicenter studies with a long-term follow-up period involving a large number of patients with MS and controls.


Asunto(s)
Biomarcadores , Esclerosis Múltiple , Estrés Oxidativo , Humanos , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/genética , Esclerosis Múltiple/patología , Animales , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/genética , Encefalomielitis Autoinmune Experimental/patología , Antioxidantes/metabolismo
5.
Rev Esp Enferm Dig ; 2024 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-38305676

RESUMEN

Hepatoid gastric adenocarcinoma (HGA) is a rare subtype of gastric cancer. It usually presents with non-specific digestive tract symptoms and is usually diagnosed in advanced stages. It has radiological and histological similarities to hepatocarcinoma (HCC), and serum elevation of alpha-fetoprotein (AFP) is characteristic, as is positive staining for this marker on immunohistochemistry. Given the low incidence and poor prognosis of this type of tumour, it is essential to make a correct differential diagnosis and to initiate early surgical treatment in localised stages and systemic treatment in those where the disease is disseminated. In this context, we present the case of a GHA diagnosed this year in our centre.

6.
RNA ; 27(12): 1557-1576, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34544891

RESUMEN

The regulation of pre-mRNA processing has important consequences for cell division and the control of cancer cell proliferation, but the underlying molecular mechanisms remain poorly understood. We report that three splicing factors, SPF45, SR140, and CHERP, form a tight physical and functionally coherent complex that regulates a variety of alternative splicing events, frequently by repressing short exons flanked by suboptimal 3' splice sites. These comprise alternative exons embedded in genes with important functions in cell-cycle progression, including the G2/M key regulator FOXM1 and the spindle regulator SPDL1. Knockdown of either of the three factors leads to G2/M arrest and to enhanced apoptosis in HeLa cells. Promoting the changes in FOXM1 or SPDL1 splicing induced by SPF45/SR140/CHERP knockdown partially recapitulates the effects on cell growth, arguing that the complex orchestrates a program of alternative splicing necessary for efficient cell proliferation.


Asunto(s)
Empalme Alternativo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Unión al ADN/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas de la Membrana/metabolismo , Factores de Empalme de ARN/metabolismo , Proteínas de Unión al ARN/metabolismo , Ribonucleoproteínas/metabolismo , Neoplasias del Cuello Uterino/patología , Apoptosis , Proteínas de Ciclo Celular/genética , Proliferación Celular , Proteínas de Unión al ADN/genética , Femenino , Células HeLa , Humanos , Proteínas de la Membrana/genética , Factores de Empalme de ARN/genética , Proteínas de Unión al ARN/genética , Ribonucleoproteínas/genética , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo
7.
J Antimicrob Chemother ; 78(3): 823-827, 2023 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-36861316

RESUMEN

INTRODUCTION: The main challenge in the treatment of Clostridioides difficile infection (CDI) is to reduce recurrence rates. Fidaxomicin improves the recurrence rate of CDI compared with vancomycin. Extended-pulsed dosing of fidaxomicin was associated with lower recurrence rates in one clinical trial but has never been directly compared with conventional fidaxomicin dosing. METHODS: To compare the recurrence rate of fidaxomicin conventional dosing (FCD) and fidaxomicin in extended-pulsed dosing (FEPD) in conditions of clinical practice at a single institution. We performed propensity score matching taking the variables age, severity and previous episode as confounders to evaluate patients with a similar recurrence risk. RESULTS: In total, 254 episodes of CDI treated with fidaxomicin were evaluated: 170 (66.9%) received FCD, and 84 (33.1%) received FEPD. More patients who received FCD were hospitalized for CDI, had severe CDI and had a diagnosis based on toxin detection. In contrast, the proportion of patients receiving proton pump inhibitors was higher in those receiving FEPD. The crude recurrence rates in FCD- and FEPD-treated patients were 20.0% and 10.7%, respectively (OR:0.48; 95% CI 0.22-1.05; P = 0.068). We did not find any differences in CDI recurrence rate in patients receiving FEPD versus FCD (OR = 0.74; 95% CI 0.27-2.04) by propensity score analysis. CONCLUSIONS: Although the recurrence rate with FEPD was numerically lower than that observed with FCD, we have not been able to show that the recurrence rate of CDI is different depending on the dosage regimen of fidaxomicin. Clinical trials or large observational studies comparing the two dosing regimens of fidaxomicin are needed.


Asunto(s)
Infecciones por Clostridium , Humanos , Infecciones por Clostridium/tratamiento farmacológico , Fidaxomicina , Instituciones de Salud , Pacientes , Puntaje de Propensión
8.
Opt Express ; 31(4): 5625-5639, 2023 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-36823837

RESUMEN

This cross-sectional and observational study includes 50 eyes of subjects with color blindness and 50 eyes of control subjects. Visual function (visual acuity, contrast sensitivity, and color vision) and neuroretinal structure were assessed in all subjects using optical coherence tomography (OCT). Significant thinning of the retinal nerve fiber layer, ganglion cell layer, and retina were observed in the color blindness group. Significant thinning was also recorded in layers that involve photoreceptor nuclei (between the outer limiting layer and the Bruch membrane and between the outer plexiform layer and the outer limiting membrane). OCT evaluation based on retinal segmentation is a rapid (5-10 minutes) non-invasive technique and seems to be a good biomarker of color blindness.


Asunto(s)
Defectos de la Visión Cromática , Visión de Colores , Humanos , Estudios Transversales , Retina , Agudeza Visual , Tomografía de Coherencia Óptica/métodos
9.
Curr Neurol Neurosci Rep ; 23(7): 361-379, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37269451

RESUMEN

PURPOSE OF REVIEW: Patients with different types of choreic syndromes, specially those with Huntington's (HD) and Wilson's (WD) diseases, report frequent sleep complaints. This review focuses on the main findings of studies addressing the sleep features in these diseases, and other less frequent causes of chorea associated with sleep disorders, including a new syndrome described in the last decade associated with IgLON5 antibodies. RECENT FINDINGS: Patients with HD and WD showed a bad quality of sleep and high frequency of insomnia and excessive daytime somnolence. WD patients also showed high scores on a specific scale for rapid eye movement sleep behavior disorders. HD and WD share decreased sleep efficiency and increased REM sleep latencies, percentage of sleep stage N1, and wake after sleep onset (WASO) among their polysomnographic features. Patients with HD and WD showed a high prevalence of different sleep disorders. Patients with other causes of chorea, including neuroacanthocytosis, parasomnia with sleep breathing disorder associated with antibodies to IgLON5, Sydenham's chorea, and choreic syndromes associated to certain genetic mutations show sleep disorders as well.


Asunto(s)
Corea , Trastorno de la Conducta del Sueño REM , Trastornos del Sueño-Vigilia , Humanos , Síndrome , Corea/complicaciones , Sueño , Trastorno de la Conducta del Sueño REM/complicaciones , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/epidemiología , Moléculas de Adhesión Celular Neuronal
10.
BMC Med Educ ; 23(1): 172, 2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-36941618

RESUMEN

BACKGROUND: Recent data on the teaching of "spirituality and health" (S/H) in medical schools are needed. In this study, we aimed to investigate the current status of S/H teaching in Brazilian medical schools, the opinions of medical directors/deans on this topic and the factors associated with its incorporation into the curriculum. METHODS: A nationwide cross-sectional survey was carried out in 2021. Information concerning the S/H content in the curricula of medical schools was obtained through medical school representatives and other sources. Medical school representatives were asked about their opinions of and barriers to S/H teaching. Regression models were used to evaluate the factors associated with the incorporation of such content into the curriculum. RESULTS: Information on the incorporation of S/H content in medical curricula was retrieved from different sources for all 342 (100%) Brazilian medical schools. Among the representatives, 150 (43.9%) completed the online form. An increase in the S/H content in Brazilian medical schools was observed (from 40% to 2011 to 65.5% in 2021). Most medical school representatives agreed that this issue is important in medical training and that more space in the curriculum is needed. However, they also observed several barriers, such as a lack of knowledge of medical teachers/faculty, a lack of time, and the topic not being included in teaching plans. The most important factors that influenced the incorporation of S/H teaching in medical schools and representatives' opinions were a lack of time and knowledge, professor preparedness and standardized national competency requirements. CONCLUSION: These results could help medical educators rethink the incorporation of S/H content into their curricula.


Asunto(s)
Facultades de Medicina , Espiritualidad , Humanos , Brasil , Estudios Transversales , Curriculum , Encuestas y Cuestionarios , Enseñanza
11.
Int J Mol Sci ; 24(23)2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38069331

RESUMEN

Perirenal adipose tissue (PRAT) surrounding the kidney is emerging as a player and novel independent risk factor in diabetic kidney disease (DKD); DKD is a complication of diabetes and is a major cause of increased cardiovascular (CV) risk and CV mortality in affected patients. We determined the effect of diabetes induction on (i) kidney and CV damage and (ii) on the expression of proinflammatory and profibrotic factors in both the PRAT and the mesenteric adipose tissue (MAT) of Munich Wistar Frömter (MWF) rats. The 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF-C) or a high-fat/high-sucrose diet for 6 weeks together with low-dose streptozotocin (15 mg/kg i.p.) at the start of dietary exposure (MWF-D). Phenotyping was performed at the end of treatment through determining water intake, urine excretion, and oral glucose tolerance; use of the homeostatic model assessment-insulin resistance index (HOMA-IR) evidenced the development of overt diabetes manifestation in MWF-D rats. The kidney damage markers Kim-1 and Ngal were significantly higher in MWF-D rats, as were the amounts of PRAT and MAT. A diabetes-induced upregulation in IL-1, IL-6, Tnf-α, and Tgf-ß was observed in both the PRAT and the MAT. Col1A1 was increased in the PRAT but not in the MAT of MWF-D, whereas IL-10 was lower and higher in the PRAT and the MAT, respectively. Urinary albumin excretion and blood pressure were not further increased by diabetes induction, while heart weight was higher in the MWF-D. In conclusion, our results show a proinflammatory and profibrotic in vivo environment in PRAT induced by diabetes which might be associated with kidney damage progression in the MWF strain.


Asunto(s)
Diabetes Mellitus , Enfermedades Renales , Humanos , Ratas , Masculino , Animales , Ratas Wistar , Albuminuria , Regulación hacia Arriba , Inflamación , Colágeno , Tejido Adiposo
12.
Int J Mol Sci ; 25(1)2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38203183

RESUMEN

To evaluate a new animal model of chronic glaucoma induced using a single injection of fibronectin-loaded biodegradable PLGA microspheres (Ms) to test prolonged therapies. 30 rats received a single injection of fibronectin-PLGA-Ms suspension (MsF) in the right eye, 10 received non-loaded PLGA-Ms suspension (Control), and 17 were non-injected (Healthy). Follow-up was performed (24 weeks), evaluating intraocular pressure (IOP), optical coherence tomography (OCT), histology and electroretinography. The right eyes underwent a progressive increase in IOP, but only induced cohorts reached hypertensive values. The three cohorts presented a progressive decrease in ganglion cell layer (GCL) thickness, corroborating physiological age-related loss of ganglion cells. Injected cohorts (MsF > Control) presented greater final GCL thickness. Histological exams explain this paradox: the MsF cohort showed lower ganglion cell counts but higher astrogliosis and immune response. A sequential trend of functional damage was recorded using scotopic electroretinography (MsF > Control > Healthy). It seems to be a function-structure correlation: in significant astrogliosis, early functional damage can be detected by electroretinography, and structural damage can be detected by histological exams but not by OCT. Males presented higher IOP and retinal and GCL thicknesses and lower electroretinography. A minimally invasive chronic glaucoma model was induced by a single injection of biodegradable Ms.


Asunto(s)
Glaucoma , Presión Intraocular , Humanos , Masculino , Animales , Ratas , Fibronectinas , Gliosis , Microesferas , Glaucoma/tratamiento farmacológico , Retina
13.
Int J Mol Sci ; 24(2)2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36674807

RESUMEN

Several papers have been published suggesting a probable role of inflammatory factors in the etiopathogenesis of migraine. In this study, we investigated the possible association between common variants in the LAG3/CD4 genes (both genes, which are closely related, encode proteins involved in inflammatory and autoimmune responses) in the risk of migraine in a cohort of Caucasian Spanish participants. For this purpose, the frequencies of CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 genotypes and allelic variants, using a specific TaqMan-based qPCR assay, were assessed in 290 patients diagnosed with migraine and in 300 healthy controls. The relationship of these variables with several clinical features of migraine was also analyzed. The frequencies of the analyzed LAG3/CD4 genotypes did not differ significantly between the two study groups and were not related to the sex, age at onset of migraine, family history of migraine, presence or absence of aura, or the triggering effect of ethanol on migraine episodes. These results suggest a lack of association between common variants in the LAG3/CD4 genes and the risk of developing migraine in the Caucasian Spanish population.


Asunto(s)
Antígenos CD4 , Predisposición Genética a la Enfermedad , Proteína del Gen 3 de Activación de Linfocitos , Trastornos Migrañosos , Humanos , Genotipo , Trastornos Migrañosos/genética , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Antígenos CD4/genética , Proteína del Gen 3 de Activación de Linfocitos/genética
14.
Rev Esp Enferm Dig ; 2023 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-37882182

RESUMEN

A 81-year-old woman with a history of mild chronic heart failure and invasive lobular breast carcinoma pT2N0M0 diagnosed in 2009 and treated by mastectomy, chemotherapy, radiotherapy and adjuvant endocrine therapy with letrozole until 2016. Since then the patient has been disease-free. She presented to the Emergency Room in April 2023 due to severe postprandial epigastric pain and a 7 kg weight loss in the last 3 months. Abdominal computed tomography was performed showing thickening of the gastric antrum and proximal duodenum walls, peritoneal implants and ascites that suggested primary gastric tumor or lymphoma as the first possibility. An endoscopic ultrasound was schedule, performing a biopsy of the gastric lesion and placing a Hot-Axios® stent. The sample showed infiltration by lobular breast carcinoma CK7 (+), CK20 (-), CDX2 (-), GATA3 (+) GCDFP15 (+) RE (+) RP (-) HER2 (-). Treatment with capecitabine was started, with which it continues currently.

15.
Eur J Clin Invest ; 52(11): e13847, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36224715

RESUMEN

BACKGROUND/OBJECTIVES: Several recent studies suggest a possible role of lymphocyte activation 3 (LAG3) protein. LAG3 can behave as an α-synuclein ligand, and serum and cerebrospinal fluid-soluble LAG3 levels have been proposed as a marker of Parkinson's disease (PD). In this study, we aimed to investigate whether there is an association between 3 common single-nucleotide variations (SNVs) in the LAG3 gene and its closely related CD4 molecule gene and the risk of PD in a Caucasian Spanish population. Two of them have been previously associated with the risk of PD in Chinese females. METHODS: We analysed genotypes and allele frequencies for CD4 rs1922452, CD4 951818 and LAG3 rs870849 SNVs, by using specifically designed TaqMan assays, in a cohort composed of 629 PD patients and 865 age- and gender-matched healthy controls. RESULTS: The frequencies of the CD4 rs1922452 A/A genotype, according to the dominant and recessive genetic models, and of the CD4 rs1922452/A allelic variant were significantly lower, and the frequencies of the CD4 rs951818 A/A genotype, according to the dominant genetic model, and of the CD4 rs951818/A allele, were significantly higher in PD patients than in controls. The differences were not significant after stratifying by sex. These two SNVs showed strong linkage. Regression models showed a lack of relation between the 3 SNVs studied and the age at onset of PD. CONCLUSIONS: These data suggest a possible role of CD4 rs1922452 and CD4 rs951818 polymorphisms in the risk of PD.


Asunto(s)
Antígenos CD/metabolismo , Enfermedad de Parkinson , alfa-Sinucleína , Antígenos CD4 , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Ligandos , Nucleótidos , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , alfa-Sinucleína/genética , Proteína del Gen 3 de Activación de Linfocitos
16.
Eur J Clin Invest ; 52(6): e13757, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35113457

RESUMEN

BACKGROUND/OBJECTIVES: Histamine has shown a possible role in the etiopathogenesis of migraine. It has been reported an association between some polymorphisms in the diamine oxidase (DAO) gene and migraine, especially in women. Two studies addressing DAO activity in migraine patients showed conflicting results. We investigated the possible relationship of serum DAO activity and histamine levels and 3 polymorphisms in the DAO gene with the risk for migraine. METHODS: We studied the frequencies of DAO rs10156191, rs1049742 and rs1049793 genotypes and allelic variants in 298 migraine patients and 360 healthy controls (using a TaqMan-based qPCR assay), and serum DAO activity and histamine levels in a subset of 99 migraine patients and 115 controls with strict exclusion criteria, and analysed the relationship of these variables with several clinical features of migraine. RESULTS: The frequencies of the DAO genotypes and allelic variants analysed were similar in migraine patients and controls. Serum DAO activity was significantly higher in migraine patients (Vmax/Km 4.24 ± 2.93 vs. 3.60 ± 7.64, p < 0.001), especially in females (Vmax/Km 4.63 ± 2.96 vs. 3.18 ± 2.32, p < 0.0001), while serum histamine was similar in both study groups. CONCLUSION: Serum DAO activity was increased in patients with migraine, especially in females, while serum histamine levels were normal. None of the studied polymorphisms was associated with the risk for migraine.


Asunto(s)
Amina Oxidasa (conteniendo Cobre) , Trastornos Migrañosos , Amina Oxidasa (conteniendo Cobre)/genética , Femenino , Genotipo , Histamina , Humanos , Trastornos Migrañosos/genética , Polimorfismo de Nucleótido Simple
17.
J Neurooncol ; 157(3): 397-403, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35378640

RESUMEN

PURPOSE: Patients suffering from recurrent and residual grade 2 (WHO) meningiomas after subtotal excision should be considered as high-risk groups with an uncertain prognosis. Adjuvant radiotherapy seems to be the best approach to reduce disease progression. The primary aim of this phase II explorative, monocentric, single arm study was to evaluate the safety of adjuvant multisession radiosurgery (mRS) in this group of patients; the efficacy in terms of tumour local control was the secondary endpoint. METHODS: Patients recruited from April 2017 to May 2019 were over 18 years old, had a histologically-documented intracranial recurrent or residual Grade 2 meningioma (WHO 2016) and a KPS > 70. Patients with NF2, concomitant neoplasm or pregnancy were excluded. Descriptive statistics were provided for categorical variables. Progression free survival (PFS) was modelled using the Kaplan-Meier method. RESULTS: Twenty-four patients were enrolled. All 24 patients underwent mRS: twenty-two patients received 28 Gy in 4 fractions, 2 patients received 24 Gy in 4 Treatment related adverse events (CTCAE 4.3) were limited to grade 2 in 1 patient (4.1%). At a median follow-up of 28 months, 8 patients (33.3%) had disease progression, either out-of-field or infield, compared with the planning target volume. Considering both infield and out-of-field progressions, 3-year PFS was 47% (95% confidence interval, CI, 22-69%); considering only the infield ones, 3-year PFS was 86% (95% CI 55-96%), and local control at last follow-up was 92%. CONCLUSION: mRS provides good local control of the tumour volume (TV) and is associated with a low rate of toxicity. These results call for further investigation to confirm favourable outcomes in patients with high-risk meningioma. TRIAL INFORMATION: NCT05081908, October 18, 2021, retrospectively registered.


Asunto(s)
Neoplasias Meníngeas , Meningioma , Radiocirugia , Adolescente , Progresión de la Enfermedad , Estudios de Seguimiento , Humanos , Neoplasias Meníngeas/patología , Meningioma/patología , Meningioma/radioterapia , Meningioma/cirugía , Radiocirugia/efectos adversos , Radiocirugia/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Organización Mundial de la Salud
18.
Int J Mol Sci ; 23(23)2022 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-36499121

RESUMEN

According to several studies, inflammatory factors could be related to the pathogenesis of idiopathic restless legs syndrome (RLS). In addition, RLS and Parkinson's disease (PD) have shown a possible relationship, and recent studies have shown an association between CD4 rs1922452 and CD4 rs951818 single nucleotide variants (SNVs) and the risk for PD. For these reasons, we investigated the possible association between common variants in the LAG3/CD4 genes (which encoded proteins involved in inflammatory and autoimmune responses) and the risk for RLS in a Caucasian Spanish population. We assessed the frequencies of CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 genotypes and allelic variants in 285 patients with idiopathic RLS and 350 healthy controls using a specific TaqMan-based qPCR assay. We also analyzed the possible influence of the genotypes' frequencies on several variables, including age at onset of RLS, gender, family history of RLS, and response to drugs commonly used in the treatment of RLS. We found a lack of association between the frequencies of genotypes and allelic variants of the 3 SNVs studied and the risk of RLS, and a weak though significant association between the CD4 rs1922452 GG genotype and an older age at onset of RLS. With the exception of this association, our findings suggest that common SNVs in the CD4/LAG3 genes are not associated with the risk of developing idiopathic RLS in Caucasian Spanish people.


Asunto(s)
Antígenos CD4 , Proteína del Gen 3 de Activación de Linfocitos , Enfermedad de Parkinson , Síndrome de las Piernas Inquietas , Humanos , Alelos , Genotipo , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , Síndrome de las Piernas Inquietas/genética , Síndrome de las Piernas Inquietas/epidemiología , Factores de Riesgo , Antígenos CD4/genética , Proteína del Gen 3 de Activación de Linfocitos/genética
19.
Int J Mol Sci ; 23(23)2022 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-36499569

RESUMEN

Several recent works have raised the possibility of the contribution of the lymphocyte activation gene 3 (LAG3) protein in the inflammatory processes of multiple sclerosis (MS). Results of studies on the possible association between LAG3 gene variants and the risk of MS have been inconclusive. In this study, we tried to show the possible association between the most common single nucleotide variants (SNVs) in the CD4 and LAG3 genes (these two genes are closely related) and the risk of MS in the Caucasian Spanish population. We studied the genotypes and allelic variants CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 in 300 patients diagnosed with MS and 400 healthy patients using specific TaqMan-based qPCR assays. We analyzed the possible influence of the genotype frequency on age at the onset of MS, the severity of MS, clinical evolutive subtypes of MS, and the HLADRB1*1501 genotype. The frequencies of the CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 genotypes and allelic variants were not associated with the risk of MS and were unrelated to gender, age at onset and severity of MS, the clinical subtype of MS, and HLADRB1*1501 genotype. The results of the current study showed a lack of association between the CD4 rs1922452, CD4 rs951818, and LAG3 rs870849 SNVs and the risk of developing MS in the Caucasian Spanish population.


Asunto(s)
Esclerosis Múltiple , Humanos , Predisposición Genética a la Enfermedad , Genotipo , Cadenas HLA-DRB1/genética , Esclerosis Múltiple/genética , Polimorfismo de Nucleótido Simple , Antígenos CD4
20.
Int J Mol Sci ; 24(1)2022 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-36613483

RESUMEN

Arterial stiffness is a major vascular complication of chronic kidney disease (CKD). The development of renal damage, hypertension, and increased pulse wave velocity (PWV) in CKD might be associated with an imbalance in bone morphogenetic proteins (BMP)-2 and BMP-7. Plasma BMP-2 and BMP-7 were determined by ELISA in CKD patients (stages I-III; n = 95) and Munich Wistar Frömter (MWF) rats. Age-matched Wistar rats were used as a control. The expression of BMP-2, BMP-7, and profibrotic and calcification factors was determined in kidney and perivascular adipose tissues (PVAT). BMP-2 was higher in stage III CKD patients compared to control subjects. BMP-7 was lower at any CKD stage compared to controls, with a significant further reduction in stage III patients. A similar imbalance was observed in MWF rats together with the increase in systolic (SBP) and diastolic blood pressure (DBP), or pulse wave velocity (PWV). MWF exhibited elevated urinary albumin excretion (UAE) and renal expression of BMP-2 or kidney damage markers, Kim-1 and Ngal, whereas renal BMP-7 was significantly lower than in Wistar rats. SBP, DBP, PWV, UAE, and plasma creatinine positively correlated with the plasma BMP-2/BMP-7 ratio. Periaortic and mesenteric PVAT from MWF rats showed an increased expression of BMP-2 and profibrotic and calcification markers compared to Wistar rats, together with a reduced BMP-7 expression. BMP-2 and BMP-7 imbalance in plasma, kidney, and PVATs is associated with vascular damage, suggesting a profibrotic/pro-calcifying propensity associated with progressive CKD. Thus, their combined analysis stratified by CKD stages might be of clinical interest to provide information about the degree of renal and vascular damage in CKD.


Asunto(s)
Insuficiencia Renal Crónica , Rigidez Vascular , Animales , Ratas , Proteína Morfogenética Ósea 7 , Riñón , Análisis de la Onda del Pulso , Ratas Wistar , Insuficiencia Renal Crónica/complicaciones
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