Thorough assessment of the effectiveness of belimumab in a large Spanish multicenter cohort of systemic lupus erythematosus patients.

OBJECTIVES: To provide an overview on the current use of belimumab (BLM) in SLE patients in clinical practice and to examine its efficacy in terms of standardized outcomes, drug survival, as well as patient and safety profiles. METHODS: A longitudinal retrospective multicentre cohort including SLE patients treated with BLM at 18 Spanish centers. Data was collected upon initiation of BLM, at 6 and 12 months after initiation, and at the last recorded visit. Changes in SLEDAI-2K, the proportion of patients who achieved LLDAS and DORIS 2021, and number of flares were compared between visits. Changes in damage, glucocorticoids use and employment status pre-BLM and post-BLM were also assessed. RESULTS: A total of 324 patients were included with a mean follow-up of 3.8 (±2.7) years. LLDAS was attained by 45.8%, 62% and 71% of patients, and DORIS by 24%, 36.2% and 52.5% on successive visits, respectively. Twenty-seven-point two percent of patients were in DORIS ≥ 50% of the visits and a 46% in LLDAS-50. Flares and number of flares were significantly lower one year after treatment with BLM and no changes in damage accrual were observed. Mean (±SD) prednisone dose was significantly reduced over time, with 70 (24%) patients discontinuing GC. CONCLUSION: Our study not only demonstrates belimumab´s efficacy in attaining treat-to-target goals in SLE patients, but also confirms its GC-sparing effect, and its prevention of flares and organ damage accrual.

Tigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production.

Multiple myeloma is an incurable plasma cell malignancy. Most patients end up relapsing and developing resistance to antineoplastic drugs, like bortezomib. Antibiotic tigecycline has activity against myeloma. This study analyzed tigecycline and bortezomib combination on cell lines and plasma cells from myeloma patients. Apoptosis, autophagic vesicles, mitochondrial mass, mitochondrial superoxide, cell cycle, and hydrogen peroxide were studied by flow cytometry. In addition, mitochondrial antioxidants and electron transport chain complexes were quantified by reverse transcription real-time PCR (RT-qPCR) or western blot. Cell metabolism and mitochondrial activity were characterized by Seahorse and RT-qPCR. We found that the addition of tigecycline to bortezomib reduces apoptosis in proportion to tigecycline concentration. Supporting this, the combination of both drugs counteracts bortezomib in vitro individual effects on the cell cycle, reduces autophagy and mitophagy markers, and reverts bortezomib-induced increase in mitochondrial superoxide. Changes in mitochondrial homeostasis and MYC upregulation may account for some of these findings. These data not only advise to avoid considering tigecycline and bortezomib combination for treating myeloma, but caution on the potential adverse impact of treating infections with this antibiotic in myeloma patients under bortezomib treatment.

Upregulated Nuclear Expression of Soluble Epoxide Hydrolase Predicts Poor Outcome in Breast Cancer Patients: Importance of the Digital Pathology Approach.

Breast cancer (BC) is the most common cancer in women, with incidence rates increasing globally in recent years. Therefore, it is important to find new molecules with prognostic and therapeutic value to improve therapeutic response and quality of life. The polyunsaturated fatty acids (PUFAs) metabolic pathway participates in various physiological processes, as well as in the development of malignancies. Although aberrancies in the PUFAs metabolic pathway have been implicated in carcinogenesis, the functional and clinical relevance of this pathway has not been well explored in BC. To evaluate the clinical significance of soluble epoxide hydrolase (EPHX2) expression in Mexican patients with BC using tissue microarrays (TMAs) and digital pathology (DP). Immunohistochemical analyses were performed on 11 TMAs with 267 BC samples to quantify this enzyme. Using DP, EPHX2 protein expression was evaluated solely in tumor areas. The association of EPHX2 with overall survival (OS) was detected through bioinformatic analysis in public databases and confirmed in our cohort via Cox regression analysis. Clear nuclear expression of EPHX2 was identified. Receiver operating characteristics (ROC) curves revealed the optimal cutoff point at 2.847062 × 10-3 pixels, with sensitivity of 69.2% and specificity of 67%. Stratification based on this cutoff value showed elevated EPHX2 expression in multiple clinicopathological features, including older age and nuclear grade, human epidermal growth factor receptor 2 (HER2) and triple negative breast cancer (TNBC) subtypes, and recurrence. Kaplan-Meier curves demonstrated how higher nuclear expression of EPHX2 predicts shorter OS. Consistently, multivariate analysis confirmed EPHX2 as an independent predictor of OS, with a hazard ratio (HR) of 3.483 and a 95% confidence interval of 1.804-6.724 (p < 0.001). Our study demonstrates for the first time that nuclear overexpression of EPHX2 is a predictor of poor prognosis in BC patients. The DP approach was instrumental in identifying this significant association. Our study provides valuable insights into the potential clinical utility of EPHX2 as a prognostic biomarker and therapeutic target in BC.

Retrospective study of acute mastoiditis in children in Spain attended in a Pediatric Emergency department.

OBJECTIVE: To analyze the cases of acute mastoiditis, characteristics, management and complications in children attended in the emergency department. METHODS: Retrospective study of acute mastoiditis in a Spanish tertiary hospital over a 6-year period (2018-2023). RESULTS: One hundred two episodes of acute mastoiditis were analyzed (54% males, median age 1.8 years). Microorganisms were isolated in one third of cases, mainly Streptococcus pyogenes (64% of ear secretion cultures). Complications occurred in 27.5%, primarily subperiosteal abscess. A younger age, absence of vaccination schedule, previous history of otitis, cochlear implant carriers or white blood cell counts and C-reactive protein levels were not associated with complications. Complicated cases had longer hospitalizations. Treatment included antibiotics, corticosteroids, and surgery in 50% of cases. CONCLUSIONS: This study shows an increase of acute mastoiditis during 2023, with a relevant role of S. pyogenes. A younger age, absence of vaccination, personal history of otitis or cochlear implant, blood cell counts and C-reactive protein levels were not associated with complications.

Biological relapse in multiple myeloma: Outcome and treatment strategies in a Spanish real-world setting.

Recommendations regarding the best time to start treatment in patients with relapsed/refractory multiple myeloma (RRMM) after biological relapse/progression (BR) are unclear. This observational, prospective, multicenter registry aimed to evaluate the impact on time to progression (TTP) of treatment initiation at BR versus at symptomatic clinical relapse (ClinR) based on the Spanish routine practice in adult patients with RRMM. Patients had two or less previous treatment lines and at least one previous partial response. Baseline characteristics and treatment outcomes were recorded, and survival was analyzed. Of 225 patients, 110 were treated at BR (TxBR group) and 115 at ClinR (TxClinR group) according to the investigators' criteria. The proportion of patients with higher ECOG, previous noncomplete remission (CR), and second relapse were significantly higher in the TxBR group compared to the TxClinR group. TheTxClinR group showed improved outcomes, including TTP, compared to the TxBR group. Progression-free survival increased in the TxClinR group (56.2 months) compared to the TxBR group (32.5 months) (p = 0.0137), and median overall survival also increased (p = 0.0897). Median TTP was significantly longer in patients relapsing from a CR (50.4 months) and in their first relapse (38.7 months) compared to those relapsing from a non-CR response (32.9 months) and in their second relapse (25.2 months). Physicians seemed to start treatment earlier in RRMM patients with poor prognosis features. Previous responses to anti-MM treatment and the number of prior treatment lines were identified as prognosis factors, whereby relapse from CR and first relapse were associated with a longer time to progression.

Influencia de la musicoterapia en la disminución de cifras tensionales moderadamente altas

Fundamento la hipertensión arterial es una enfermedad con alta prevalencia a nivel mundial. Entre las alternativas para su tratamiento, la musicoterapia resulta eficaz junto al tratamiento farmacológico. Objetivo describir la influencia de la musicoterapia en la disminución de cifras tensionales moderadamente altas. Métodos se realizó un estudio observacional, analítico, de casos y controles, con pacientes (n=100) que acudieron al Cuerpo de guardia del Policlínico Rolando Ricardo Estrada, del municipio de Báguanos (Holguín), en el período 2021-2022, seleccionados mediante un muestreo no probabilístico intencional. Fueron creados dos grupos de 50 pacientes cada uno. El grupo de casos fue expuesto a la musicoterapia, no así el de control. Resultados en ambos grupos predominaron los pacientes con edades entre 40 y 59 años (41 %), del sexo femenino (55 %) y con diagnóstico previo de hipertensión arterial (58 %). En el momento de acudir al policlínico, en los dos grupos predominó la presión sistólica entre 140 y 159 mmHg (62 %). Luego de haber transcurrido una hora, en la mayoría de los pacientes del grupo de casos las cifras bajaron hasta 120 y 139 mmHg (32 %). En el grupo control se evidenció una leve disminución, pero se mantuvo mayor porcentaje de pacientes con 140 a 159 mmHg (25 %). Conclusión los pacientes expuestos a la musicoterapia evidenciaron una disminución más marcada de las cifras tensionales moderadamente elevadas, en comparación con los no expuestos.

Background arterial hypertension is a disease with a high prevalence worldwide. Among the alternatives for its treatment, music therapy is effective together with pharmacological treatment. Objective to describe the music therapy influence in the reduction of moderately high blood pressure figures. Methods an observational, analytical, case-control study was carried out with patients (n=100) who attended the Rolando Ricardo Estrada Polyclinic's Emergency Room, in the Báguanos municipality (Holguín), from 2021 to 2022, selected through purposive non- probabilistic sampling. Two groups of 50 patients each were created. The case group was exposed to music therapy, but not the control group. Results in both groups, patients aged between 40 and 59 years (41%), female (55%) and with a previous diagnosis of arterial hypertension (58%) predominated. At the time of going to the polyclinic, systolic pressure between 140 and 159 mmHg (62%) predominated in both groups. After one hour had elapsed, in most of the patients in the case group the figures dropped to 120 and 139 mmHg (32%). In the control group, a slight decrease was observed, but a higher percentage of patients with 140 to 159 mmHg (25%) remained. Conclusion patients exposed to music therapy showed a more marked decrease in moderately elevated blood pressure figures, compared to those not exposed.

Pénfigo vulgar / Pemphigus vulgaris

Imágenes(AU)

Amputación digital en una paciente con úlcera del pie diabético / Digital amputation in a patient with diabetic foot ulcer

Este artículo consta solo de imágenes(AU)

Carga do tabagismo no Brasil e benefício potencial do aumento de impostos sobre os cigarros para a economia e para a redução de mortes e adoecimento / Carga del tabaquismo en Brasil y beneficio potencial del aumento de impuestos sobre el tabaco para la economía y para la reducción de muertes por enfermedad / Burden of smoking in Brazil and potential benefit of increasing taxes on cigarettes for the economy and for reducing morbidity and mortality

A prevalência do tabagismo no Brasil reduziu sobremaneira nas últimas décadas, mas o país ainda tem uma elevada carga de doença associada a este fator de risco. O objetivo deste trabalho foi estimar a carga de mortalidade, morbidade e custos para a sociedade associada ao tabagismo em 2015 e o potencial impacto gerado em desfechos de saúde e para a economia a partir do aumento de preços dos cigarros por meio de impostos. Foram desenvolvidos dois modelos: o primeiro é um modelo matemático baseado em uma microssimulação probabilística de milhares de indivíduos usando-se coortes hipotéticas que considerou a história natural, custos e a qualidade de vida destes indivíduos. O segundo é um modelo de impostos aplicado para estimar o benefício econômico e em desfechos de saúde de diferentes cenários de aumento de preços em 10 anos. O tabagismo foi responsável por 156.337 mortes, 4,2 milhões de anos de vida perdidos, 229.071 infartos agudos do miocárdio, 59.509 acidentes vasculares cerebrais e 77.500 diagnósticos de câncer. O custo total foi de R$ 56,9 bilhões, dos quais 70% corresponderam ao custo direto associado à assistência à saúde e o restante ao custo indireto devido à perda de produtividade por morte prematura e incapacidade. Um aumento de 50% do preço do cigarro evitaria 136.482 mortes, 507.451 casos de doenças cardiovasculares, 64.382 de casos de câncer e 100.365 acidentes vasculares cerebrais. O benefício econômico estimado seria de R$ 97,9 bilhões. Concluiu-se que a carga da doença e econômica associada ao tabagismo é elevada no Brasil e o aumento de impostos é capaz de evitar mortes, adoecimento e custos para a sociedade.

La prevalencia del tabaquismo en Brasil se redujo sobremanera en las últimas décadas, pero el país todavía cuenta con una elevada carga de enfermedad asociada a este factor de riesgo. El objetivo de este trabajo fue estimar la carga de mortalidad, morbilidad y costes para la sociedad, asociada al tabaquismo en 2015, y el impacto potencial generado en los desenlaces de salud y para la economía a partir del aumento de precios del tabaco a través de impuestos. Se desarrollaron dos modelos: el primero es un modelo matemático, basado en una microsimulación probabilística de millares de individuos, a través de cohortes hipotéticas, que consideró la historia natural, costes y calidad de vida de esos individuos. El segundo se trata de un modelo de impuestos aplicado para estimar el beneficio económico y en desenlaces de salud de diferentes escenarios con el aumento de precios durante 10 años. El tabaquismo fue responsable de 156.337 muertes, 4,2 millones de años de vida perdidos, 229.071 infartos agudos de miocardio, 59.509 accidentes vasculares cerebrales y 77.500 diagnósticos de cáncer. El coste total fue de BRL 56,9 billones (USD 14,7 billones), de los cuales un 70% correspondieron al coste directo asociado a la asistencia a la salud y lo restante al coste indirecto, debido a la pérdida de productividad por muerte prematura e incapacidad. Un aumento de un 50% del precio del tabaco evitaría 136.482 muertes, 507.451 casos de enfermedades cardiovasculares, 64.382 de casos de cáncer y 100.365 accidentes vasculares cerebrales. El beneficio económico estimado sería de BRL 97,9 billones (USD 25,5 billones). Se concluyó que la carga de la enfermedad y económica asociada al tabaquismo es elevada en Brasil y el aumento de impuestos es capaz de evitar muertes, enfermedad y costes para la sociedad.

The prevalence of smoking in Brazil has decreased considerably in recent decades, but the country still has a high burden of disease associated with this risk factor. The study aimed to estimate the burden of mortality, morbidity, and costs for society associated with smoking in 2015 and the potential impact on health outcomes and the economy based on price increases for cigarettes through taxes. Two models were developed: the first is a mathematical model based on a probabilistic microsimulation of thousands of individuals using hypothetical cohorts that considered the natural history, costs, and quality of life of these individuals. The second is a tax model applied to estimate the economic benefit and health outcomes in different price increase scenarios in 10 years. Smoking was responsible for 156,337 deaths, 4.2 million years of potential life lost, 229,071 acute myocardial infarctions, 59,509 strokes, and 77,500 cancer diagnoses. The total cost was BRL 56.9 billion (USD 14.7 billion), with 70% corresponding to the direct cost associated with healthcare and the rest to indirect cost due to lost productivity from premature death and disability. A 50% increase in cigarette prices would avoid 136,482 deaths, 507,451 cases of cardiovascular diseases, 64,382 cases of cancer, and 100,365 cases of stroke. The estimated economic benefit would be BRL 97.9 billion (USD 25.5 billion). In conclusion, the burden of disease and economic losses associated with smoking is high in Brazil, and tax increases are capable of averting deaths, illness, and costs to society.

Carga de enfermedad atribuible al uso del tabaco en Paraguay y potencial impacto sanitario y económico del aumento del precio a través de impuestos / Burden of disease attributable to tobacco use in Paraguay, and potential health and financial impact of increasing prices through taxing

RESUMEN Objetivos. Estimar la carga de enfermedad asociada al consumo de tabaco en Paraguay y evaluar el potencial efecto económico y sanitario del aumento de precio mediante impuestos. Materiales y métodos. Se diseñó un modelo de microsimulación de Monte Carlo que incorporó la historia natural, costos y calidad de vida de enfermedades asociadas al tabaquismo para el 2015. Asimismo, se estimó el impacto en varios escenarios de aumento de impuestos sobre la prevalencia de tabaquismo y la recaudación fiscal. Resultados. 3354 personas mueren al año en Paraguay por consecuencia del tabaquismo. El 19 % de las muertes son por enfermedad isquémica cardíaca, el 15 % por accidentes cerebrovasculares. El 77 % de las muertes por enfermedad pulmonar obstructiva crónica y el 83 % de cáncer de pulmón son atribuibles al tabaquismo. Estas enfermedades en Paraguay representan un costo médico directo anual de más de 1,5 x 106 millones de guaraníes, mientras la recaudación impositiva por la venta de cigarrillos apenas llega a cubrir un 20 % de este gasto. Un aumento en el precio de los cigarrillos del 50 % vía impuestos, podría llevar a evitar 2507 muertes en diez años y generar recursos por 2,4 x 106 millones por ahorro en gastos sanitarios y aumento de recaudación. Conclusiones. El costo y la carga de enfermedad asociado al consumo de tabaco en el sistema de salud es elevado en Paraguay. Un aumento del precio de los cigarrillos a través de los impuestos tendría importantes beneficios sanitarios y podría compensar parcialmente los costos sanitarios.

ABSTRACT Objectives . To consider the burden of disease associated to tobacco consumption in Paraguay and to evaluate the potential economic and health effect of price increase through taxes. Materials and Methods . A Monte Carlo simulation model was designed incorporating natural history, costs, and quality of life of diseases associated to smoking for 2015. Also, several scenarios were considered for the impact of tax raises on the prevalence of smoking and fiscal collection. Results . In Paraguay, 3,354 people die every year as a consequence of smoking. Nineteen percent of deaths are due to cardiac ischemia, 15% due to stroke. 77% of deaths due to chronic obstructive pulmonary disease (COPD), and 83% of lung cancer can be attributed to smoking. These diseases in Paraguay represent an annual direct medical cost of more than 1.5 trillion PYG, while the tax collection from cigarette sales barely covers 20% of this expense. A 50% increase in the price of cigarettes via taxes could avoid 2507 deaths in ten years and generate resources by 2.4 trillion in savings in health expenses and tax of collection. Conclusions . The cost and the burden of disease associated to tobacco consumption is high in the health system in Paraguay. An increase in cigarette price through taxes could have significant health benefits and could offset health costs in part.

Zika y casos de microcefalia en el estado Zulia: aspectos clínicos y epidemiológicos del brote, año 2016 / Zika and cases of microcephaly in the state of Zulia: clinical and epidemiological aspects of the sprout, year 2016

El Zika es una enfermedad emergente en Venezuela y en el estado Zulia, evoluciona generalmente de manera benigna y puede producir complicaciones como síndrome Guillain Barré y microcefalia en recién nacidos. Se plantea describir los aspectos clínicos, epidemiológicos del brote de Zika y los casos de microcefalia. La investigación es descriptiva, transversal, realizada de mayo 2016 a marzo 2017. La población fue de 1.155 casos sospechosos, la muestra 228 pacientes, resultando 108 positivos por PCR en tiempo real. El mayor número de casos se presentó en la edad de 17 a 33 años (59,3%), predomina el sexo femenino (81,5%), en los municipios Maracaibo y San Francisco (75%). En relación a la sintomatología, la frecuencia fue erupción (84,3%), cefalea y fiebre (76,9%), menos común la artralgia (65,7%) y mialgias (47,2%). Durante el brote, se presentaron dos muertes del sexo masculino, representando el 1,9%; 146 casos con el síndrome de Guillain Barré y 7 casos con microcefalia correspondiente al sexo masculino (85%), con una edad gestacional del recién nacido de 37,4 semanas y sobrevida de 85%. La principal recomendación, debe estar orientada al control del vector transmisor de la enfermedad y hacer el diagnóstico de los casos sospechosos para su confirmación.

Zika is an emerging disease in Venezuela and in the state of Zulia, it generally evolves in a benign manner and can produce complications such as Guillain-Barré syndrome and microcephaly in newborns. Itis proposed to describe the clinical and epidemiological aspects of the Zika outbreak and the cases of microcephaly. The research is descriptive, cross-sectional, conducted from May 2016 to March 2017. The population consisted of 1,155 suspected cases, with a sample of 228 patients, resulting in 108 positive PCR in real time. The largest number of cases occurred at the age of 17 to 33 years (59.3%), with a predominance of females (81.5%), in the municipalities of Maracaibo and San Francisco (75%). In relation to the symptomatology, the frequent are rash (84.3%), headache and fever (76.9%), while arthralgia (65.7%) and myalgia (47.2%) are less common. During the outbreak, there were two deaths of the male sex, representing 1.9%; 146 cases with Guillain-Barré syndrome and 7 cases with microcephaly, corresponding to the male sex (85%), with a newborn gestational age of 37.4 weeks and 85% survival. The main recommendation should be directed to the control of the transmitting vector of the disease and to make the diagnosis of the suspicious cases for their confirmation.

Allergies: diseases closely related to cancer / Alergias: enfermedades estrechamente relacionadas con el cáncer

Abstract: Allergies are hypersensitivity reactions that occur through specific type Th2 immunological mechanisms characterized by different soluble mediators, as well as specific cells of the immune system. In recent decades, evidence has emerged relating this disease with cancer development. However, most of the results of epidemiology studies have been controversial and contradictory. There are mainly two trends. While the first indicates that allergies can reduce the risk of cancer, the other indicates that they may increase this risk. The first trend can be explained by the immunosurveillance hypothesis, which states that the increased immune surveillance after the immune hyper-responsiveness can inhibit or exert a protective effect against the development of cancer. Similarly, the prophylaxis hypothesis suggests that the physical effects of allergy symptoms can prevent cancer by removing potential carcinogens. In contrast, the opposing hypothesis propose that there is a deviation of the immune response toward Th2, which favors the development of cancer, or that the process of chronic inflammation favors the generation of mutations, and therefore the development of cancer. With the purpose of understanding more about these two hypotheses, the main soluble and cellular factors of allergic diseases that could be playing a key role in the development or inhibition of cancer were considered in this review.

Resumen: Las alergias son reacciones de hipersensibilidad que ocurren mediante mecanismos inmunológicos específicos de tipo Th2. Se caracterizan por distintos mediadores solubles, así como células específicas del sistema inmune. En las últimas décadas ha surgido evidencia que asocia esta enfermedad con el desarrollo de cáncer. Sin embargo, los resultados obtenidos, en su mayoría de estudios epidemiológicos, han sido controversiales y contradictorios. Lo anterior se debe a que existen dos principales tendencias. Mientras algunos estudios han demostrado que las alergias pueden reducir el riesgo de cáncer, otros estudios muestran que puede aumentarlo. Lo primero puede explicarse por la hipótesis de inmunovigilancia, que establece que el aumento de la vigilancia después de la hiperreactividad inmune puede inhibir o ejercer un efecto protector contra el desarrollo de cáncer. Del mismo modo, la hipótesis de la profilaxis sugiere que los efectos físicos de síntomas de las alergias pueden prevenir el cáncer mediante la eliminación de los carcinógenos potenciales. Las hipótesis opuestas proponen que existe un desvío de la respuesta inmune hacia Th2 lo cual favorece el desarrollo del cáncer, o que el proceso de inflamación crónica favorece la generación de mutaciones, y por tanto el desarrollo del cáncer. Con el propósito de entender más acerca de estas dos hipótesis, en esta revisión se consideraron los principales factores solubles y celulares de las enfermedades alérgicas que pudieran estar desempeñando un papel clave en el desarrollo o inhibición del cáncer.