Evaluation of a risk-sharing agreement for atezolizumab treatment in patients with non-small cell lung cancer: a strategy to improve access in low-income countries.

BACKGROUND: Using immune checkpoint inhibitors (IO) is a promising approach to maximize clinical benefits for patients with non-small cell lung cancer (NSCLC). PD-L1 expression serves as a predictive factor for treatment outcomes with IO. However, the high cost of this treatment creates significant barriers to access. Substantial evidence demonstrates the sustained clinical benefits experienced by patients who respond to immunotherapy. While IOs show promise in NSCLC treatment, their high cost poses access barriers. AIM: This study focused on a prospective cost analysis conducted at a high-specialty health facility to assess the economic implications of implementing a risk-sharing agreement (RSA) for atezolizumab in NSCLC. METHODS: The study included 30 patients with advanced NSCLC, with the pharmaceutical company funding the initial cycles. If patients responded, a government program covered costs until disease progression. RESULTS: A median progression-free survival of 4.67 months across populations, rising to 9.4 months for responders. The 2-year overall survival rate for the response group was 64%, significantly higher than for non-response. Without an RSA, a total treatment cost of $881 859.36 ($29 395.31/patient) was reported, compared to $530 467.12 ($17 682.24/patient) with an RSA, representing a 40% cost reduction. In responders, the average cost per year of life per patient dropped by 22%. Risk-sharing, assessed through non-parametric tests, showed a statistically significant difference in pharmacological costs (P < .001). CONCLUSION: Implementing RSAs can optimize resource allocation, making IO treatment more accessible, especially in low-income countries.

Perilesional edema diameter associated with brain metastases as a predictive factor of response to radiotherapy in non-small cell lung cancer.

Background: Different prognostic scales exist in patients with brain metastasis, particularly in lung cancer. The Graded Prognostic Assessment for lung cancer using molecular markers (Lung-molGPA index) for brain metastases is a powerful prognostic tool that effectively identifies patients at different risks. However, these scales do not include perilesional edema diameter (PED) associated with brain metastasis. Current evidence suggests that PED might compromise the delivery and efficacy of radiotherapy to treat BM. This study explored the association between radiotherapy efficacy, PED extent, and gross tumor diameter (GTD). Aim: The aim of this study was to evaluate the intracranial response (iORR), intracranial progression-free survival (iPFS), and overall survival (OS) according to the extent of PED and GT. Methods: Out of 114 patients with BM at baseline or throughout the disease, 65 were eligible for the response assessment. The GTD and PED sum were measured at BM diagnosis and after radiotherapy treatment. According to a receiver operating characteristic (ROC) curve analysis, cutoff values were set at 27 mm and 17 mm for PED and GT, respectively. Results: Minor PED was independently associated with a better iORR [78.8% vs. 50%, OR 3.71 (95% CI 1.26-10.99); p = 0.018] to brain radiotherapy. Median iPFS was significantly shorter in patients with major PED [6.9 vs. 11.8 months, HR 2.9 (95% CI 1.7-4.4); p < 0.001] independently of other prognostic variables like the Lung-molGPA and GTD. A major PED also negatively impacted the median OS [18.4 vs. 7.9 months, HR 2.1 (95% CI 1.4-3.3); p = 0.001]. Conclusion: Higher PED was associated with an increased risk of intracranial progression and a lesser probability of responding to brain radiotherapy in patients with metastatic lung cancer. We encourage prospective studies to confirm our findings.

Neuroinflammation, Microbiota-Gut-Brain Axis, and Depression: The Vicious Circle.

Depression is the leading cause of disability worldwide, contributing to the global disease burden. From above, it is a priority to investigate models that fully explain its physiopathology to develop new treatments. In the last decade, many studies have shown that gut microbiota (GM) dysbiosis influences brain functions and participate, in association with immunity, in the pathogenesis of depression. Thereby, GM modulation could be a novel therapeutic target for depression. This review aims to evidence how the GM and the immune system influence mental illness, particularly depression. Here, we focus on the communication mechanisms between the intestine and the brain and the impact on the development of neuroinflammation contributing to the development of Major Depressive Disorder (MDD). However, most of the current findings are in animal models, suggesting the need for studies in humans. In addition, more analysis of metabolites and cytokines are needed to identify new pathophysiological mechanisms improving anti-depression treatments.

Cytokine and microbiota profiles in obesity-related hypertension patients.

Background: Systemic arterial hypertension is linked to a heightened risk of cardiovascular diseases on a global scale. In Mexico, nearly half of adults in vulnerable conditions experience hypertension. Imbalance in the oral and intestinal microbiota composition has been observed in patients with hypertension, documented by a decrease of bacteria producing short-chain fatty acids, which play a critical role in blood pressure regulation. Aim: To examine the cytokines' profile and assess the characteristics of oral and gut microbiota in obesity-related hypertension in Mexican patients. Methods: A cross-sectional, observational, and analytical study was carried out. Twenty-two patients were categorized by their body mass index (BMI) as overweight and obese, and the diagnosis of primary hypertension. DNA from supragingival dental plaque and feces samples was used to carry out 16S rRNA sequencing. Additionally, 13 cytokines were quantified. Results: In the oral microbiota, Kluyvera was found to be significantly enriched in obese compared to overweight patients. Instead, the gut microbiota was dominated by Firmicutes. However, the correlation between certain genera and proinflammatory cytokines was noted. Conclusion: This exploratory study provides insights into the complex relationship between the oral and gut microbiota and their association with systemic inflammation in obesity-related hypertension.

Overexpression of proinflammatory cytokines in dental pulp tissue and distinct bacterial microbiota in carious teeth of Mexican Individuals.

The prevalence of dental caries in the Mexican adult population aged 20 to 85 years is around 93.3%, and 50% in Mexican children and adolescents. Worldwide, it is the most common non-communicable disease. One of the main etiological factors for dental caries is the oral microbiome and changes in its structure and function, with an expansion of pathogenic bacteria like Streptococcus mutans. The exposed dental pulp tissue triggers an innate immune response to counteract this bacterial invasion. The relation between oral dysbiosis and innate immune responses remains unclear. We aimed to understand the relationship between innate immune response and the oral microbiota by quantifying the expression of Toll-like receptors (TLRs) and proinflammatory markers (cytokines and a chemokine) in dental pulp tissue, either exposed or not to carious dentin, and to correlate this information with the oral microbiome found in healthy teeth and those with moderate caries. RNA was purified from pulp tissue, subjected to RT-qPCR and analysed with the ΔΔCt method. Supragingival dental plaque of non-carious teeth and dentin of carious teeth were subjected to 16S targeted sequencing. Principal coordinate analysis, permutational multivariate ANOVA, and linear discriminant analysis were used to assess differences between non-carious and carious teeth. Correlations were assessed with Spearman´s test and corrected for multiple comparisons using the FDR method. The relative abundance (RA) of Lactobacillus, Actinomyces, Prevotella, and Mitsuokella was increased in carious teeth; while the RA of Haemophilus and Porphyromonas decreased. Olsenella and Parascardovia were only detected in carious teeth. Significant overexpression of interleukin 1 beta (IL1 ß), IL6, and CXCL8 was detected in pulp tissue exposed to carious dentin. IL1ß correlated positively with TLR2 and Actinomyces; yet negatively with Porphyromonas. These findings suggest that immune response of pulp tissue chronically exposed to cariogenic microbiome is triggered by proinflammatory cytokines IL1ß and IL6 and the chemokine CXCL8.

Microbioma oral: variabilidad entre regiones y poblaciones / Oral Microbiome: Variability Between Regions and Populations

Resumen De acuerdo con la Organización Mundial de la Salud (OMS), 3.58 billones de personas son afectadas por desórdenes orales, donde la caries, seguida de la enfermedad periodontal son las más frecuentes y las principales causas de daño al tejido pulpar y pérdida de órganos dentales. En México, el Sistema de Vigilancia Epidemiológica de Patologías Bucales (SIVEPAB) reportó que el 53% de la población se ve afectada por algún grado de enfermedad periodontal, mientras que en promedio la caries afecta al 93.3% de la población de entre 20 a 85 años y más, así como a alrededor del 50.0% de niños y adolescentes, por lo que ambos padecimientos son considerados un problema de salud pública importante en este país. Adicionalmente, se sabe que el microbioma oral humano está asociado con la salud y la enfermedad bucodental. Entre los géneros bacterianos que comúnmente habitan la cavidad oral humana destacan Streptococcus spp., Lactobacillus spp. y Porphyromonas spp. que, a través del desequilibrio del microbioma oral (disbiosis), se asocian con la caries o la enfermedad periodontal. En vista de que estamos constantemente expuestos a este tipo de infecciones crónicas inflamatorias, se sabe que las bacterias orales se trasladan a otras partes del cuerpo contribuyendo al desarrollo y exacerbación de la inflamación sistémica y otras enfermedades. Ya que existen factores como la ubicación geográfica, además de la disbiosis, la edad, la dieta y la genética, que influyen en la variabilidad del microbioma humano. Es importante analizar la diversidad del microbioma oral desde esta perspectiva, ya que el conocimiento que se tiene hasta el momento aún es escaso; por lo anterior se realizó una búsqueda de artículos publicados entre 2010 y 2020 en poblaciones de Asia, África, América y Europa, con el fin de responder la siguiente pregunta: ¿el factor geográfico tiene un impacto en la composición de la variabilidad del microbioma oral humano?

Abstract According to the World Health Organization (WHO), 3.58 billion people were affected by oral disorders, where caries, followed by periodontal disease are the most frequent and the main causes of damage to pulp tissue and loss of dental organs. In Mexico, the Epidemiological Surveillance System for Oral Pathologies (SIVEPAB) reported that 53% of the population is affected by some degree of periodontal disease, while on average caries affects 93.3% of the population between 20 and 85 years old and older, as well as about 50.0% of children and adolescents, so both conditions are considered an important public health problem in this country. Additionally, the human oral microbiome is known to be associated with oral health and disease. An imbalance in the oral microbiome (dysbiosis) can result in the proliferation of Streptococcus mutans and Porphyromonas gingivalis, linked to caries and periodontal disease. The latter two conditions, the most prevalent oral diseases worldwide, are the main causes of damage to pulp tissue and loss of dental organs. In the presence of these pathologies, constant exposure to the corresponding inflammatory chronic infection could lead to the translocation of oral bacteria to other parts of the body, where they may contribute to the development and/or exacerbation of systemic inflammation and trigger disease. Since age, diet, genetics, and geographical location are known to influence the variability of the human microbiome, it is important to analyze differences in the oral microbiome between distinct populations. Up to now, little attention has been given to this task. The current review carried out for articles published between 2010 and 2020 and describes the human oral microbiome in populations of Asia, Africa, America and Europa, to explore whether geographical differences have an impact on the variability of the human oral microbiome.