Prognostic Implications of the Residual Tumor Microenvironment after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Patients without Pathological Complete Response.

With a high risk of relapse and death, and a poor or absent response to therapeutics, the triple-negative breast cancer (TNBC) subtype is particularly challenging, especially in patients who cannot achieve a pathological complete response (pCR) after neoadjuvant chemotherapy (NAC). Although the tumor microenvironment (TME) is known to influence disease progression and the effectiveness of therapeutics, its predictive and prognostic potential remains uncertain. This work aimed to define the residual TME profile after NAC of a retrospective cohort with 96 TNBC patients by immunohistochemical staining (cell markers) and chromogenic in situ hybridization (genetic markers). Kaplan-Meier curves were used to estimate the influence of the selected TME markers on five-year overall survival (OS) and relapse-free survival (RFS) probabilities. The risks of each variable being associated with relapse and death were determined through univariate and multivariate Cox analyses. We describe a unique tumor-infiltrating immune profile with high levels of lymphocytes (CD4, FOXP3) and dendritic cells (CD21, CD1a and CD83) that are valuable prognostic factors in post-NAC TNBC patients. Our study also demonstrates the value of considering not only cellular but also genetic TME markers such as MUC-1 and CXCL13 in routine clinical diagnosis to refine prognosis modelling.

Multicenter Real-World Data of Subsequent Chemotherapy after Progression to PARP Inhibitors in a Maintenance Relapse Setting.

Background: Despite impressive progression-free survival (PFS) results from PARP inhibitors (PARPi) in ovarian cancer, concerns about their effect on post-progression treatment outcomes have recently arisen, particularly when administered in the relapsed setting. Overlapping mechanisms of resistance between PARPi and platinum have been described, and optimal therapies upon progression to PARPi are unknown. We communicate real-world data (RWD) on outcomes of subsequent chemotherapy upon progression to PARPi used as maintenance in ovarian cancer relapses, particularly focusing on platinum rechallenge, according to BRCA status. Methods: Data from high-grade serous or endometrioid ovarian cancer patients who received subsequent chemotherapy after progression to maintenance PARPi in the relapsed setting, in 16 Catalan hospitals between August 2016 and April 2021, and who were followed-up until July 2021, were included. Endpoints were overall response rate (ORR), and PFS and overall survival (OS) measured from the subsequent chemotherapy starting date. Results: 111 patients were included [46 (41.4%) presented pathological BRCA1/2 mutations, 8 (7.5%) in other homologous recombination-related genes]. Sixty-four patients (57.7%) had received two prior chemotherapy lines, including the one immediately prior to PARPi. PARPi were niraparib (n = 60, 54.1%), olaparib (n = 49, 44.1%), and rucaparib (n = 2, 1.8%). A total of 81 patients remained platinum-sensitive (PS population) after progression to PARPi (when progression-free interval [PFI] was >6 months after the last cycle of prior platinum) [median PFI 12.0 months (interquartile range, IQR, 8.8−17.1)]. Of those, 74 were treated with subsequent platinum regimens, with the following results: ORR of 41.9%, median PFS (mPFS) of 6.6 months (95% CI 6−9.2), and median OS (mOS) of 20.6 months (95% CI 13.6−28.9). Analysis of these 74 patients according to BRCA status showed that PFIs for BRCA mutant and non BRCA-mutant patients were 13.6 [IQR11.2−22.2] and 10.3 [IQR 7.4−14.9] months, respectively (p = 0.010); ORR were 40.0% versus 43.6%, respectively; Rates of progression (as best response) to subsequent platinum were 45.7% versus 17.9%, respectively (p = 0.004); mPFS and mOS were 3.5 (95% CI 2.5−8.6) versus 7.5 months (95% CI 6.5−10.1, p = 0.03), and 16.4 (95% CI 9.3−27.5) versus 24.2 months (95% CI 17.2−NR, p = 0.036), respectively. Conclusion: This is the largest series of real-world data on ovarian cancer patients retreated with platinum in the post-PARPi scenario, separately analyzing BRCA mutant and non-mutant patients, to our knowledge. In our platinum-sensitive population, rechallenge with platinum after progression upon PARPi in the 3rd or later lines for ovarian cancer relapses shows relevant ORR and similar PFS outcomes to historical series of the prePARPi era. However, BRCA mutant patients presented significantly higher rates of progression under subsequent platinum and worse survival outcomes associated with subsequent platinum than non-BRCA-mutant patients.

Differential Tolerance and Seasonal Adaptation to Temperature and Salinity Stress at a Dynamic Range Boundary Between Estuarine Gastropods.

AbstractInsight into how coastal organisms will respond to changing temperature and salinity regimes may be derived from studies of adaptation to fluctuating estuarine environments, especially under stressful range-edge conditions. We characterized a dynamic range boundary between two estuarine sea slugs, Alderia modesta (distributed across the North Pacific and North Atlantic) and Alderia willowi, known from southern and central California. The species overlap from Bodega Bay to San Francisco Bay, where populations are dominated by A. modesta after winter rains but by A. willowi after peak summer temperatures. Laboratory assays confirmed superior tolerance to low salinity for the northern species, A. modesta: encapsulated embryos developed at 8 ppt, larvae survived at 4-6 ppt, and adults survived repeated exposure to 2 ppt, salinities that reduced development or survival for the same stages of A. willowi. Adults did not appreciably differ in their high-temperature threshold, however. Each species showed increased tolerance to either temperature or salinity stress at its range margin, indicating plasticity or local adaptation, but at the cost of reduced tolerance to the other stressor. At its northern limit, A. willowi became more tolerant of low salinity during the winter rainy season, but also less heat tolerant. Conversely, A. modesta became more heat resistant from spring to summer at its southern limit, but less tolerant of low salinity. Trade-offs in stress tolerance may generally constrain adaptation and limit biotic response to a rapidly changing environment, as well as differentiating species niches.

Phubbing en las Relaciones Románticas: Uso del Celular, Satisfacción en la Pareja, Bienestar Psicológico y Salud Mental / Phubbing in Romantic Relationships: Cell Phone Use, Couple Satisfaction, Psychological Well-Being and Mental Health

El propósito del estudio fue examinar si el uso frecuente del celular (phubbing) impacta directamente la satisfacción en las relaciones románticas e indirectamente el bienestar psicológico y la salud mental de los puertorriqueños. El Estudio 1 analiza las propiedades psicométricas de la Escala de Phubbing en la Pareja y de la Escala de Conflictos Relacionados al Uso del Celular. Los análisis demostraron que las escalas son confiables y válidas. El Estudio 2 evaluó el objetivo principal del estudio con una muestra no probabilística de 392 puertorriqueñas seleccionados por disponibilidad. Los resultados confirmaron el rol mediador que tiene la satisfacción en la relación de pareja entre el phubbing, el bienestar psicológico y la salud mental. En general, los participantes que reportaron mayor phubbing, mostraban menor satisfacción en la relación de pareja, mayor sintomatología asociada a depresión, ansiedad y estrés, y menor bienestar psicológico. Nuestro estudio aporta evidencia sobre el efecto negativo que puede tener el uso desmedido del celular en las relaciones románticas, así como en la salud mental de los individuos.

The purpose of this study was to evaluate if frequent cell phone use (phubbing) has a direct impact in the couple's satisfaction, and an indirect effect on the psychological well-being and mental health of Puerto Rican. Study 1 examines the psychometric properties of the Partner Phubbing Scale and the Cell Phone Conflict Scale. The scales were found to be highly reliable and valid. Study 2 assessed the study's proposed relationships among a non-probabilistic sample of 392 Puerto Ricans, selected by availability. The results showed a significant mediation of couple's satisfaction in the relationship between phubbing, psychological well-being and mental health. Overall, participants who rated more phubbing in their relationships also reported lower couple's satisfaction, more symptoms related to depression, anxiety and stress, and lower psychological well-being. Our study provides empirical evidence on the negative effect of excessive use of cell phones within romantic relationships, as well on people's mental health.

Complicaciones neurológicas del paciente con cáncer / No disponible

Los avances de las últimas décadas tanto en el diagnóstico como en tratamiento del cáncer han conseguido aumentar la supervivencia, lo que ha conllevado un aumento de las complicaciones neurológicas. Estas complicaciones pueden ser debidas tanto al propio cáncer como al tratamiento y en ocasiones son la primera manifestación de la enfermedad oncológica. Algunas de estas complicaciones son potencialmente reversibles por ello el diagnóstico precoz y su tratamiento correcto pueden mejorar los síntomas neurológicos y la calidad de vida de estos pacientes. En el presente artículo haremos una revisión de las principales complicaciones neurológicas del paciente con cáncer con una orientación diagnóstica y terapéutica (AU)

The advances of recent decades in the diagnosis and treatment of cancer have managed to increase survival, but this has produced an increase in neurological complications. These complications can be caused by cancer and its treatment and sometimes can be the first manifestation of cancer disease. Some of these complications are potentially reversible so that early diagnosis and proper treatment can improve the neurological symptoms and quality of life of these patients. In this article we will review major neurological complications of cancer patients and also do a diagnostic and therapeutic orientation (AU)

A dose-dependent role for EBF1 in repressing non-B-cell-specific genes.

In the absence of early B-cell factor 1 (EBF1), B-cell development is arrested at an uncommitted progenitor stage that exhibits increased lineage potentials. Previously, we investigated the roles of EBF1 and its DNA-binding partner Runx1 by evaluating B lymphopoiesis in single (EBF1(het) and Runx1(het)) and compound haploinsufficent (Ebf1(+/-) Runx1(+/-), ER(het)) mice. Here, we demonstrate that decreased Ebf1 gene dosage results in the inappropriate expression of NK-cell lineage-specific genes in B-cell progenitors. Moreover, prolonged expression of Ly6a/Sca-1 suggested the maintenance of a relatively undifferentiated phenotype. These effects were exacerbated by reduced expression of Runx1 and occurred despite expression of Pax5. Repression of inappropriately expressed genes was restored in most pre-B and all immature B cells of ER(het) mice. Enforced EBF1 expression repressed promiscuous transcription in pro-B cells of ER(het) mice and in Ebf1(-/-) Pax5(-/-) fetal liver cells. Together, our studies suggest that normal levels of EBF1 are critical for maintaining B-cell identity by directing repression of non-B-cell-specific genes.