Racial disparities in neutrophil counts among patients with metastatic breast cancer during treatment with CDK4/6 inhibitors.

PURPOSE: The three CDK4/6 inhibitors (CDK4/6i) approved for use in HR-positive/HER2-negative metastatic breast cancer (MBC), palbociclib, ribociclib, and abemaciclib, are generally well tolerated; however, neutropenia is a common toxicity. Within the general population, neutropenia has been shown to be more common in individuals of African descent. The landmark CDK4/6i trials in MBC lacked racial diversity in their patient populations. We aimed to assess the toxicity profiles of CDK4/6is in a racially diverse population. METHODS: We conducted a retrospective study at Montefiore Medical Center in patients with HR-positive/HER2-negative MBC prescribed CDK4/6i as first or subsequent line therapy between January 2015 and April 2020. Baseline characteristics and laboratory data at various treatment timepoints were collected. RESULTS: The final analysis included 182 patients, of whom 46% were Black. Baseline absolute neutrophil count (ANC) was lower in the Black vs. Non-Black cohort (p = 0.001) but the change in ANC from baseline (delta-ANC) was smaller in the Black cohort, and the ANC at different treatment timepoints was similar between groups. There was no difference in the rate of infection or number of dose delays/reductions between racial groups. We did not find any difference in PFS between Black and Non-Black groups, regardless of the presence of CDK4/6i-induced neutropenia. CONCLUSION: We analyzed toxicity profiles of 182 patients with HR-positive/HER2-negative MBC treated with CDK4/6i. Despite the lower baseline ANC seen in our Black cohort, treatment toxicities were similar between racial groups. Long-term outcomes with CDK4/6i therapy, measured by PFS, were similar between Black vs. Non-Black patients.

Circulating tumor cells et al.: towards a comprehensive liquid biopsy approach in breast cancer.

Liquid biopsy has emerged as a crucial tool in managing breast cancer (BC) patients, offering a minimally invasive approach to detect circulating tumor biomarkers. Until recently, the majority of the studies in BC focused on evaluating a single liquid biopsy analyte, primarily circulating tumor DNA and circulating tumor cells (CTCs). Despite the proven prognostic and predictive value of CTCs, their low abundance when detected using enrichment methods, especially in the early stages, poses a significant challenge. It is becoming evident that combining diverse circulating biomarkers, each representing different facets of tumor biology, has the potential to enhance the management of patients with BC. This article emphasizes the importance of considering these biomarkers as complementary/synergistic rather than competitive, recognizing their ability to contribute to a comprehensive disease profile. The review provides an overview of the clinical significance of simultaneously analyzing CTCs and other biomarkers, including cell-free circulating DNA, extracellular vesicles, non-canonical CTCs, cell-free RNAs, and non-malignant cells. Such a comprehensive liquid biopsy approach holds promise not only in BC but also in other cancer types, offering opportunities for early detection, prognostication, and therapy monitoring. However, addressing associated challenges, such as refining detection methods and establishing standardized protocols, is crucial for realizing the full potential of liquid biopsy in transforming our understanding and approach to BC. As the field evolves, collaborative efforts will be instrumental in unlocking the revolutionary impact of liquid biopsy in BC research and management.

Latest advances in clinical studies of circulating tumor cells in early and metastatic breast cancer.

Circulating tumor cells (CTCs) have emerged as a promising biomarker in breast cancer, offering insights into disease progression and treatment response. While CTCs have demonstrated prognostic relevance in early breast cancer, more validation is required to establish optimal cut-off points. In metastatic breast cancer, the detection of CTCs using the Food and Drug Administration-approved CellSearch® system is a strong independent prognostic factor. However, mesenchymal CTCs and the Parsortix® PC1 system show promise as alternative detection methods. This chapter offers a comprehensive review of clinical studies on CTCs in breast cancer, emphasizing their prognostic and predictive value in different stages of the disease and provides insights into potential future directions in CTC research.

Reduction of the ATPase inhibitory factor 1 (IF1) leads to visual impairment in vertebrates.

In vertebrates, mitochondria are tightly preserved energy producing organelles, which sustain nervous system development and function. The understanding of proteins that regulate their homoeostasis in complex animals is therefore critical and doing so via means of systemic analysis pivotal to inform pathophysiological conditions associated with mitochondrial deficiency. With the goal to decipher the role of the ATPase inhibitory factor 1 (IF1) in brain development, we employed the zebrafish as elected model reporting that the Atpif1a-/- zebrafish mutant, pinotage (pnt tq209 ), which lacks one of the two IF1 paralogous, exhibits visual impairment alongside increased apoptotic bodies and neuroinflammation in both brain and retina. This associates with increased processing of the dynamin-like GTPase optic atrophy 1 (OPA1), whose ablation is a direct cause of inherited optic atrophy. Defects in vision associated with the processing of OPA1 are specular in Atpif1-/- mice thus confirming a regulatory axis, which interlinks IF1 and OPA1 in the definition of mitochondrial fitness and specialised brain functions. This study unveils a functional relay between IF1 and OPA1 in central nervous system besides representing an example of how the zebrafish model could be harnessed to infer the activity of mitochondrial proteins during development.

[Intravesical botulinum toxin under local anestesia as ambulatory procedure.] / Toxina botulínica intravescal con anestesia local como procedimiento ambulante.

Bladder hyperactivity is described as the presence of "voiding urgency, generally associated with increased daytime frequency and nocturia, with or without urinary incontinence, in the absence of urinary tract infection or other obvious pathology". Onabotulinum toxin A (BTA) is a recommendable therapeutic option in case of failure, contraindication or refusal of the conservative therapy or other non-pharmacological therapies. The injection of BTA in the detrusor has been performed under local, regional or general anesthesia either in the conventional or major ambulatory surgery operative room or in the cystoscopy room. The objective of this paper is to describe the procedure to perform BTA therapy as an ambulatory operation under intravesical local anesthesia in the cystoscopy room, describing its advantages and limitations.

Tormenta eléctrica y torsade de pointes asociados a tratamiento con antimoniales en un paciente con leishmaniasis cutánea / Electrical storm and torsade de pointes associated with antimonial treatment in a patient with cutaneous leishmaniasis

Resumen La toxicidad por antimoniales puede comprometer múltiples sistemas y llega a ser potencialmente fatal. Se presenta el caso de un joven militar quien durante el tratamiento de su segundo episodio de leishmaniasis cutánea presentó toxicidad pancreática y cardiaca, desarrollando un síndrome de QT largo adquirido y tormenta eléctrica con episodios frecuentes de taquicardia ventricular que incluían torsade de pointes. Se realizó tratamiento en unidad de cuidados intensivos, donde requirió múltiples descargas de desfibrilador y la administración de sulfato de magnesio hasta la resolución del cuadro clínico.

Abstract The toxicity due to antimonial can compromise multiple systems, and is potentially fatal. The case is presented of a young soldier, who had pancreatic and cardiac toxicity during the treatment of his second episode of cutaneous leishmaniasis. This developed into an acquired long QT syndrome and an electrical storm with frequent episodes of ventricular that included torsade de pointes. Treatment was given in the Intensive Care Unit, where he required multiple defibrillator discharges and the administering of magnesium sulphate until the clinical symptoms were resolved.

Caracterización clínica de los pacientes con síncope / Clinical profile of patients with syncope

Resumen Introducción: Se hizo una caracterización clínica de los pacientes con síncope en un Hospital Universitario en Bogotá. Objetivo: Describir las características clínicas de los pacientes con síncope que consultaron al Hospital Militar Central en Bogotá en el período 2012-2015, y analizar la contribución de las ayudas diagnósticas y de las escalas EGSYS y OESIL para orientar el diagnóstico etiológico. Métodos: Se realizó un estudio observacional, descriptivo, de pacientes mayores de 18 años que ingresaron a urgencias del Hospital Militar Central por síncope; se analizaron características clínicas, estudios solicitados y puntajes de las escalas EGSYS y OESIL. Resultados: Se evaluaron 705 historias clínicas, de las cuales 116 fueron excluidas por datos faltantes; la edad promedio fue 58 años y el 46,52% eran mujeres. El 41,6% tenía hipertensión arterial y el 21% enfermedad cardiaca previa. Según el diagnóstico etiológico, 75% fueron clasificados como síncope no cardiaco, 23% como síncope cardiaco y en 2% no se identificó la etiología. El examen más solicitado fue el electrocardiograma (79%), seguido por troponina (63%) y TAC cerebral (58%). Al aplicar las escalas, 60% de los pacientes tuvo un puntaje menor a 3 (EGSYS) y 2 puntos (OESIL), lo que sugería que eran de etiología no cardiogénica/bajo riesgo de mortalidad respectivamente. Conclusiones: La etiología del síncope en la mayoría de los casos fue no cardiaca. El electrocardiograma debe ser solicitado a todos los pacientes con síncope. El uso rutinario de las escalas de riesgo puede contribuir a disminuir la solicitud de estudios no indicados, optimizar el uso de recursos y reducir los días de hospitalización.

Abstract Introduction: A clinical profile was constructed on patients with syncope in a Bogota University Hospital. Objective: To describe the clinical characteristics of patients with syncope that were seen in the Hospital Militar Central in Bogota in the period 2012-2015, as well as to analyse the contribution of diagnostic aids and the Evaluation of Guidelines in Syncope Study (EGSYS) and the Lazio epidemiological syncope Observation (OESIL) scores in order to determine the aetiological diagnosis. Methods: A descriptive observational study was performed on patients over 18 years admitted to the Emergency Department of the Hospital Militar Central due to syncope. An analysis was carried out on the clinical characteristics, examinations requested, and the scores on the EGSYS and OESI L scales. Results: A total of 705 clinical histories were evaluated, of which 116 were excluded due to lack of data. The mean age was 58 years, and 46.52% were women. Arterial hypertension was observed in 41.6%, and 21% had a previous heart disease. According to the aetiological diagnosis, 75% were classified as non-cardiac syncope, 23% as cardiac syncope, and 2% of unknown origin. The most requested examination was the electrocardiogram (79%), followed by troponin (63%), and a computed tomography brain scan (58%). On applying the scales, 60% of the patients had a score of less than 3 (EGSYS) and 2 points (OESIL), which suggested that they were of non-cardiogenic origin/low mortality risk, respectively. Conclusions: The origin of syncope in the majority of cases was non-cardiac. An electrocardiogram must be requested on all patients with syncope. The routine use of risk scales can contribute to reducing the number of non-indicated examinations, as well as optimise the use of resources and reduce hospital stay.