Proton pump inhibitors decrease efficacy of palbociclib in patients with metastatic breast.

OBJECTIVES: The objective of this investigation was to assess the impact of concurrent proton pump inhibitors (PPIs) on progression-free survival (PFS) in patients with hormone receptor-positive and HER2-negative metastatic breast cancer (mBC) who received palbociclib as first-line or successives therapy. MATERIALS AND METHODS: A retrospective observational study was conducted, enrolling patients diagnosed with estrogen receptor-positive, human epidermal growth factor receptor 2-negative mBC, and eligible for palbociclib treatment. Patients were categorized as "concurrent PPIs" if they received PPIs for at least two-thirds of the palbociclib therapy duration, and as "no concurrent PPIs" if they did not receive PPIs during the course of palbociclib treatment. RESULTS: A total of 165 patients were included in the study. Among first-line patients treated with palbociclib, those using concurrent PPIs exhibited a PFS of 8.88 months, while patients using palbociclib without concurrent PPIs had a PFS of 67.81 months (p < 0.0001). In second-line or subsequent treatments, patients on palbociclib with concurrent PPIs had a PFS of 7.46 months, whereas those using palbociclib without concurrent PPIs had a PFS of 17.29 months (p = 0.122). CONCLUSION: This study demonstrates that the concurrent use of PPIs in mBC patients receiving palbociclib negatively affects PFS, particularly in the first-line setting. Nevertheless, further investigation is warranted to explore the impact of PPIs on cycle-dependent kinase 4/6 inhibitors.

Concurrent functional ultrasound imaging with graphene-based DC-coupled electrophysiology as a platform to study slow brain signals and cerebral blood flow under control and pathophysiological brain states.

Current methodology used to investigate how shifts in brain states associated with regional cerebral blood volume (CBV) change in deep brain areas, are limited by either the spatiotemporal resolution of the CBV techniques, and/or compatibility with electrophysiological recordings; particularly in relation to spontaneous brain activity and the study of individual events. Additionally, infraslow brain signals (<0.1 Hz), including spreading depolarisations, DC-shifts and infraslow oscillations (ISO), are poorly captured by traditional AC-coupled electrographic recordings; yet these very slow brain signals can profoundly change CBV. To gain an improved understanding of how infraslow brain signals couple to CBV we present a new method for concurrent CBV with wide bandwidth electrophysiological mapping using simultaneous functional ultrasound imaging (fUS) and graphene-based field effect transistor (gFET) DC-coupled electrophysiological acquisitions. To validate the feasibility of this methodology visually-evoked neurovascular coupling (NVC) responses were examined. gFET recordings are not affected by concurrent fUS imaging, and epidural placement of gFET arrays within the imaging window did not deteriorate fUS signal quality. To examine directly the impact of infra-slow potential shifts on CBV, cortical spreading depolarisations (CSDs) were induced. A biphasic pattern of decreased, followed by increased CBV, propagating throughout the ipsilateral cortex, and a delayed decrease in deeper subcortical brain regions was observed. In a model of acute seizures, CBV oscillations were observed prior to seizure initiation. Individual seizures occurred on the rising phase of both infraslow brain signal and CBV oscillations. When seizures co-occurred with CSDs, CBV responses were larger in amplitude, with delayed CBV decreases in subcortical structures. Overall, our data demonstrate that gFETs are highly compatible with fUS and allow concurrent examination of wide bandwidth electrophysiology and CBV. This graphene-enabled technological advance has the potential to improve our understanding of how infraslow brain signals relate to CBV changes in control and pathological brain states.

Ethanol Solvation of Polymer Residues in Graphene Solution-Gated Field Effect Transistors.

The persistence of photoresist residues from microfabrication procedures causes significant obstacles in the technological advancement of graphene-based electronic devices. These residues induce undesired chemical doping effects, diminish carrier mobility, and deteriorate the signal-to-noise ratio, making them critical in certain contexts, including sensing and electrical recording applications. In graphene solution-gated field-effect transistors (gSGFETs), the presence of polymer contaminants makes it difficult to perform precise electrical measurements, introducing response variability and calibration challenges. Given the absence of viable short to midterm alternatives to polymer-intensive microfabrication techniques, a postpatterning treatment involving THF and ethanol solvents was evaluated, with ethanol being the most effective, environmentally sustainable, and safe method for residue removal. Employing a comprehensive analysis with XPS, AFM, and Raman spectroscopy, together with electrical characterization, we investigated the influence of residual polymers on graphene surface properties and transistor functionality. Ethanol treatment exhibited a pronounced enhancement in gSGFET performance, as evidenced by a shift in the charge neutrality point and reduced dispersion. This systematic cleaning methodology holds the potential to improve the reproducibility and precision in the manufacturing of graphene devices. Particularly, by using ethanol for residue removal, we align our methodology with the principles of green chemistry, minimizing environmental impact while advancing diverse graphene technology applications.

Gender, smoking, and tobacco cessation with pharmacological treatment in a cluster randomized clinical trial.

INTRODUCTION: Whether men find it easier to quit smoking than women is still controversial. Different studies have reported that the efficacy of pharmacological treatments could be different between men and women. This study conducted a secondary analysis of 'Subsidized pharmacological treatment for smoking cessation by the Spanish public health system' (FTFT-AP study) to evaluate the effectiveness of a drug-funded intervention for smoking cessation by gender. METHODS: A pragmatic randomized clinical trial by clusters was used. The population included smokers aged ≥18 years, smoking >10 cigarettes per day, randomly assigned to an intervention group receiving regular practice and financed pharmacological treatment, or to a control group receiving only regular practice. The main outcome was continued abstinence at 12 months, self-reported and validated with CO-oximetry. The percentage, with 95% confidence intervals, of continued abstinence was compared between both groups at 12 months post-intervention, by gender and the pharmacological treatment used. Multilevel logistic regression analysis was performed. RESULTS: A total of 1154 patients from 29 healthcare centers were included. The average age was 46 years (SD=11.78) and 51.7% were men. Overall, the self-reported abstinence at 12 months was 11.1% (62) in women and 15.7% (93) in men (AOR=1.4; 95% CI: 1.0-2.0), and abstinence validated by CO-oximetry was 4.6% (26) and 5.9% (35) in women and men, respectively (OR=1.3; 95% CI: 0.7-2.2). In the group of smokers receiving nicotine replacement treatment, self-reported abstinence was higher in men compared to women (29.5% vs 13.5%, OR=2.7; 95% CI: 1.3-5.8). CONCLUSIONS: The effectiveness of a drug-financed intervention for smoking cessation was greater in men, who also showed better results in self-reported abstinence with nicotine replacement treatment.

Leptina y artritis reumatoide, influencia de esta adipocina en la enfermedad

La artritis reumatoide es una enfermedad autoinmune inflamatoria, en cuya fisiopatología participan tanto factores ambientales como genéticos, teniendo como principales citocinas involucradas la interleucina 1, interleucina 6 y el factor de necrosis tumoral. Los pacientes con artritis reumatoide tienen hasta 2 a 3 veces mayor riesgo cardiovascular que la población en general, este riesgo es equiparable al de los pacientes con diabetes mellitus. Este aumento en la morbilidad cardiovascular se explica tanto por una mayor prevalencia de los factores de riesgo tradicionales, como por factores de riesgo no tradicionales. La obesidad o el exceso de tejido adiposo es un factor de riesgo que puede influir en el aumento del riesgo cardiovascular, esto debido a una mala regulación metabólica, aumento de la hipertensión arterial, dislipidemia, ácidos grasos libres circulantes y a la producción de citocinas. Últimamente ha surgido un amplío interés en estudiar la relación entre la artritis reumatoide y las adipocinas, sin embargo los resultados han sido heterogéneos, debido a la poca homogeneidad en los grupos de estudio. El objetivo de la siguiente revisión es hablar acerca de la influencia que tiene la leptina en la artritis reumatoide, en su fisiopatología, en la actividad de la enfermedad y en el aumento del riesgo cardiovascular.

Rheumatoid arthritis is an inflammatory autoimmune disease which physiopathology both an environmental and genetic factors are involved, having as main cytokines involved the interleukin 1, interleukin 6 and tumor necrosis factor. Patients with rheumatoid arthritis have up to 2 - 3 times higher cardiovascular risk than the overall population, this risk is comparable to that of patients with diabetes mellitus. This increase in cardiovascular morbidity is explained by a higher prevalence of traditional risk factors, as well as non-traditional risk factors. Obesity or excessive fat tissue is a risk factor that can influence the increased cardiovascular risk, this due to poor metabolic regulation, increased blood pressure, dyslipidemia, free fatty acids circulating and cytokine production. Lately has emerged a broad interest in studying the relationship between rheumatoid arthritis and adipokines, however the results have been heterogeneous, due to the lack of homogeneity in the study groups. The aim of the following review is to talk about the influence of leptin in rheumatoid arthritis, in its pathophysiology, in the disease activity and in the increased cardiovascular risk.

Neurolupus and pregnancy: An ethical and therapeutic dilemma in a second level hospital / Neurolupus y embarazo: un dilema ético y terapéutico en un hospital de segundo nivel

Optic neuritis secondary to systemic lupus erythematosus is a rare manifestation with a prevalence of 1%. The case described concerns a patient who presented with optic neuritis associated with SLE. She was 19 weeks pregnant, and required pulses with methyl-prednisolone and cyclophosphamide, which are within the category D drugs used during pregnancy. Three weeks later, she presented with uterine activity, and went into labor, with a fetus of 22 weeks gestation and weighing 430 g being obtained, which died 48 h later. In medical practice there are ethical guidelines and economic obstacles to carrying out diagnostic and therapeutic protocols established by limiting clinical practice

La neuritis óptica secundaria a lupus eritematoso sistémico es una rara manifestación con una prevalencia del 1%. Presentamos el caso de una paciente que mostró neuritis óptica asociada a lupus eritematoso sistémico, con 19 semanas de gestación, requiriendo de pulsos de metilprednisolona y ciclofosfamida, que se encuentran dentro de los medicamentos categoría D utilizados durante el embarazo. Tres semanas después presentó actividad uterina y posteriormente trabajo de parto obteniéndose un producto de 22 semanas de gestación y 430 g, falleciendo a las 48 h. En la práctica médica existen lineamientos éticos y obstáculos económicos que limitan la realización de protocolos diagnósticos y terapéuticos establecidos, limitando la práctica clínica

Riesgo cardiovascular en lupus eritematoso sistémico / Cardiovascular risk in systemic lupus erythematosus

Antecedentes: Los pacientes con lupus eritematoso sistémico (LES) tienen mayor frecuencia de factores de riesgo cardiovascular (RCV) tradicionales, esto sumado a la presencia de factores de RCV no tradicionales, aumenta la probabilidad de eventos cardiacos hasta 5 veces. Objetivo: Determinar la frecuencia de los factores de RCV en una población de pacientes con LES. Materiales y métodos: Se realizó un estudio descriptivo, transversal, observacional, en 51 pacientes con diagnóstico de LES. Resultados: Se reportó el patrón lúpico de dislipoproteinemia ya que el 52,9% presentó hipoal-falipoproteinemia, 49% hipercolesterolemia, 35,3% hipertrigliceridemia y 19,6% elevación de c-LDL. Con respecto a las comorbilidades el 31,4% presentó obesidad, 27,5% hipertensión arterial y 6% diabetes mellitus. Los factores de RCV no tradicionales que predominaron fueron los asociados con la actividad de la enfermedad, el 90,1% tomaba glucocorticoides, 70,6% presentó niveles bajos de C3, 66,7% tuvo PCR > 2 mg/l, 56,9% tenía más de 4 puntos de SLEDAI-2 K, 41,2% presentó niveles bajos de C4, 29,4% tenía más de 10 arios de duración de la enfermedad, 25,5% tenía nefritis lúpica. Con lo que respecta a la presencia de anticuerpos asociados a RCV el 58,8, 9,8, 74,8 y el 3,9% presentaron anti-Smith, anticoagulante lúpico, anti-beta 2 glicoproteína I, anticardiolipinas positivas, respectivamente. Conclusiones: Los pacientes con LES presentan un estado proinflamatorio y aterogénico, aumentando el riesgo de desarrollar enfermedades cardiovasculares tanto por mayor incidencia de los factores de riesgo tradicionales, como por la presencia de factores que promueven una inflamación crónica.

Background: Patients with systemic lupus erythematosus (SLE) have a higher frequency of traditional cardiovascular risk factors (CVR). This, combined with the presence of nontraditional cardiovascular risk factors, increases the probability of cardiac events by five times. Objective: To determine the prevalence of CVR factors in a population of patients with SLE. Material and methods: A descriptive, cross-sectional, observational study in 51 patients with the diagnosis of SLE. Results: A lupus dyslipoproteinaemia pattern was reported, of which 52.9% had hypo-alphalipoproteinaemia, 49% hypercholesterolaemia, 35.3% hypertriglyceridaemia, and 19.6% with an elevated c-LDL. The comorbidities found were, 31.4% with obesity, 27.5% with high blood pressure, and 6% suffered from diabetes mellitus. Predominant non-traditional CVR factors were associated with disease activity, with 90.1% taking glucocorticoids, 70.6% had low levels of complement C3, 41.2% had low levels of complement C4, 66.7% had a CRP > 2 mg/l, 56.9% had a SLEDAI-2 K score greater than 4 points, 29.4% had more than 10 years of disease duration, and 25.5% had lupus nephritis. As regards the presence of antibodies associated with CVR, 58.8, 9.8, 74.8 and 3.9% had anti-Smith antibodies, lupus anticoagulant, antibeta2glycoprotein I, and positive anticardiolipin, respectively. Conclusions: Patients with SLE have a pro-inflammatory and atherogenic state, increasing the risk of developing cardiovascular diseases, and therefore a higher incidence of traditional risk factors, such as the presence of factors that promote chronic inflammation.