Concurrent Use of Abemaciclib and Radiotherapy in Metastatic Breast Cancer Patients: A Single-Center Experience.

INTRODUCTION: There is little evidence regarding the safety and efficacy of the combination of abemaciclib plus radiotherapy (RT). The majority of studies investigated the combination of RT with palbociclib or ribociclib reporting that hematological toxicity is common. Given the unique toxicity profile of abemaciclib with greater gastrointestinal toxicity compared to hematological toxicity, we wanted to evaluate the toxicity of the combination with RT in metastatic breast cancer (BC) patients. METHODS: Patients with histologically proven metastatic or locally advanced BC treated with RT and concurrent abemaciclib were selected. Toxicity was assessed according to the NCI-CTCAE V4.0. RESULTS: Thirty-two metastatic sites were treated in 19 patients and analyzed. All patients received abemaciclib during the RT course. A total of 68% of patients received a full dose of abemaciclib during RT. Also, 71.9% of patients received a palliative intent (median dose = 30 Gy, range = 8-30 Gy), and 26.3% were treated for 9 oligo-metastatic or oligo-progressive sites of disease with stereotactic body RT (median dose = 30 Gy, range 21-30 Gy, given in 3-5 fractions). Overall, the rate of G3 toxicity was 15.7%. The rate of G3 hematological toxicity was 10.6% (2/19 patients, one G3 neutropenia and one G3 anemia). No patient presented diarrhea, including those treated for RT sites close to the bowel. One patient developed G3 skin toxicity. Pain significantly improved after RT (mean value NRS pre-RT = 3.9, SD = 3.07; mean value NRS after RT = 0.9, SD = 0.46; p < 0.0001). CONCLUSION: Abemaciclib and concomitant RT seem well tolerated showing acceptable toxicity.

Vessel-wall MRI in primary headaches: The role of neurogenic inflammation.

OBJECTIVE: The purpose of this study was to investigate if vessel-wall magnetic resonance imaging (VW-MRI) could differentiate among primary headaches disorders, such as migraine and cluster headache (CH), and detect the presence of neurogenic inflammation. BACKGROUND: The pathophysiology of primary headaches disorders is complex and not completely clarified. The activation of nociceptive trigeminal afferents through the release of vasoactive neuropeptides, termed "neurogenic inflammation," has been hypothesized. VW-MRI can identify vessel wall changes, reflecting the inflammatory remodeling of the vessel walls despite different etiologies. METHODS: In this case series, we enrolled seven patients with migraine and eight patients with CH. They underwent a VW-MRI study before and after the intravenous administration of contrast medium, during and outside a migraine attack or cluster period. Two expert neuroradiologists analyzed the magnetic resonance imaging (MRI) studies to identify the presence of vessel wall enhancement or other vascular abnormalities. RESULTS: Fourteen out of 15 patients had no enhancement. One out of 15, with migraine, showed a focal parietal enhancement in the intracranial portion of a vertebral artery, unmodified during and outside the attack, thus attributable to atherosclerosis. No contrast enhancement attributable to neurogenic inflammation was observed in VW-MRI, both during and outside the attack/cluster in all patients. Moreover, MRI angiography registered slight diffuse vasoconstriction in one of seven patients with migraine during the attack and in one of eight patients with cluster headache during the cluster period; both patients had taken triptans as symptomatic therapy for pain. CONCLUSIONS: These preliminary results suggest that VW-MRI studies are negative in patients with primary headache disorders even during migraine attacks or cluster periods. The VW-MRI studies did not detect signs of neurogenic inflammation in the intracranial intradural vessels of patients with migraine or CH.

New steps on an old path: Novel estrogen receptor inhibitors in breast cancer.

Estrogen receptor (ER) signaling represents the main driver of tumor growth and survival in hormone receptor positive (HR+) breast cancer (BC). Thus, endocrine therapy (ET) alone or in combination with targeted agents constitutes the mainstay of the treatment for this BC subtype. Despite its efficacy, intrinsic or acquired resistance to ET occurs in a large proportion of cases, mainly due to aberrant activation of ER signaling (i.e. through ligand-independent ER activation, in the presence of estrogen receptor 1 (ESR1) gene aberration or ER protein phosphorylation) and/or the upregulation of escape pathways, such as the PI3K/AKT/mTOR pathway. Therefore, the development of new ER pathway targeting agents remains essential to delay and overcome ET resistance, enhance treatment efficacy and tolerability, and ultimately prolong patient survival and improve their quality of life. Several novel ER targeting agents are currently under investigation. Among these, the oral selective ER degraders (SERDs) represent the pharmacological class at the most advanced stage of development and promise to enrich the therapeutic armamentarium of HR+ BC in the next few years, as they showed promising results in several clinical trials, either as single ET agents or in combination with targeted therapies. In this manuscript, we aim to provide a comprehensive overview on the clinical development of novel ER targeting agents, reporting the most up-to-date evidence on oral SERDs and other compounds, including new selective ER modulators (SERMs), ER proteolysis targeting chimera (PROTACs), selective ER covalent antagonists (SERCAs), complete ER antagonists (CERANs), selective human ER partial agonists (ShERPAs). Furthermore, we discuss the potential implications of introducing these novel treatment strategies in the evolving and complex therapeutic scenario of HR+ BC.

Vessel-wall MRI in thunderclap headache: A useful tool to answer the riddle?

BACKGROUND: Finding an intracranial aneurysm (IA) during a thunderclap headache (TCH) attack, represents a problem because it is necessary to distinguish whether the aneurysm is responsible for the headache as a warning leak or as an incidental finding. High-Resolution Vessel-Wall (HRVW) MRI sequences have been proposed to assess the stability of the wall, as it permits to detect the presence of aneurysmal wall enhancement (AWE). In fact, AWE has been confirmed due to inflammation, recognizable preceding rupture.Case 1: A 37-year-old woman with a migraine more intense than her usual. A CTA revealed a 10 mm AComA aneurysm without subarachnoid hemorrhage (SAH) and HRVW-MRI excluded AWE. The patient's headache improved, and therefore, the aneurysm was considered an incidental finding, and the headache diagnosed as TCH attack. Subsequently, the aneurysm was surgically clipped, and typical migraine relapsed was reported at follow-up (FU).Case 2: A 67-year-old woman with no history of headaches underwent CTA for an abrupt onset of headache. A 7 mm right carotid-ophthalmic aneurysm with no sign of SAH was discovered. HRVW-MRI demonstrated AWE and thus, a TCH attack for a warning leak of an unstable wall was suspected. Endovascular coiling was immediately performed and at FU any further headache attack was reported. CONCLUSIONS: HRVW-MRI is useful in case of finding aneurysm as the cause of headaches, particularly the TCH attack. In fact, HRVW-MRI could assess the stability of the aneurysms wall, allowing different patient management and eventually the aneurysmal treatment.

Eficacia de la cánula nasal de alto flujo en patologías respiratorias / Efficiency of high flow nasal cannula in pediatric respiratory pathologies

Introducción: En la edad pediátrica hay factores predisponentes importantes que hacen a los niños ser más vulnerables a presentar insuficiencia respiratoria aguda (IRA). Objetivo: Demostrar los beneficios del uso de la cánula nasal de alto flujo (CNAF) en pacientes menores de 5 años con IRA secundaria a enfermedades respiratorias y admitidos a la unidad de cuidados intensivos pediátricos (UCIP). Sujetos y Métodos: Estudio analítico observacional de cohortes mixtas, donde una cohorte esta formada por un grupo expuesto a la CNAF evaluada de manera prospectiva, mientras se comparo con una cohorte histórica. Resultados: 138 pacientes fueron admitidos al estudio de los cuales 69 fueron casos manejados con CNAF y 69 fueron controles que no estuvieron expuestos al uso de la CNAF pero sí a otros modos de ventilación mecánica invasiva. Los días de oxigenoterapia fueron estadísticamente menores en el grupo de casos de 13 (DE 8.01) días a 22 (DE 20.7) días en el grupo control (P = <0.05). Al igual los días de UCIP y los días totales de hospitalización fueron menores en el grupo manejado con CNAF (P = 0.011 y P = 0.001, respectivamente), con una media de tiempo de 10 (DE 7.8) días en UCIP y 17 (DE 9.25) días intrahospitalarios para el grupo de casos versus 14 (DE 10.1) días en UCIP y 28 (DE 23.9) días intrahospitalarios para el grupo control. Conclusión: La CNAF es un método de soporte respiratorio no invasivo, efectivo y fácil de usar en la población pediátrica con IRA secundario a diversas patologías respiratorias.

Introduction: During pediatric ages there are important predisposing factors that make children more vulnerable to present acute respiratory failure (ARF). Objective: Determine the benefits of the use of high flow nasal cannula (HFNC) in patients younger than 5 years with ARF, secondary to respiratory diseases and admitted to the pediatric intensive care unit (PICU). Subjects and Method: Analytical observational study of mixed type cohorts, where a cohort is formed by the group exposed to HFNC and evaluated prospectively, while it was compared with a historical cohort. Results: 138 patients were admitted to the study of which 69 were cases handled with HFNC and 69 were controls who were not exposed to the use of HFNC but to other types of invasive mechanical ventilation. Oxygen therapy days were statistically shorter in the case group from 13 (SD 8.01) days to 22 (SD 20.7) days in the control group (P = <0.05). The length of stay in PICU and the total inpatient days were lower in the group managed with HFNC (P = 0.011, P = 0.001), with a mean time of 10 (SD 7.8) days in PICU and 17 (SD 9.25) inpatient days for the case group versus 14 (SD 10.1) days in PICU and 28 (SD 23.9) inpatient days for the control group. Conclusion: HFNC system is a non-invasive respiratory support method, simple, effective and easy to use in the pediatric population less than 5 years of age with ARF due to various respiratory diseases.

Lesión traqueobronquial secundaria a trauma torácico cerrado en paciente pediátrico: Reporte de un caso / Tracheobronchial injury, secondary to blunt thoracic trauma in a pediatric patient: A case report

Las lesiones traqueobronquiales son raras y presentan un alto índice de mortalidad, falleciendo el 80% antes de llegar al hospital por lo cual existen pocos reportes de casos. Se describe que alrededor del 80% de los casos se pueden manejar con maniobras no quirúrgicas o manejo quirúrgico tardío. Del 15% al 20% ameritará manejo quirúrgico temprano y al ser estos de mayor gravedad presentarán un alto riesgo de complicaciones posteriores. En esta revisión presentamos un caso de lesión traqueobronquial secundaria a trauma torácico cerrado manejado en la unidad de terapia intensiva de nuestro hospital que requirió corrección quirúrgica temprana y presento complicaciones tardías que al final la llevaron a su fallecimiento.

Tracheobronchial injuries are rare and have a high mortality rate, 80% dying before reaching the hospital, so there are few case reports. It is described that about 80% of cases can be managed with non-surgical maneuvers or late surgical management. From 15% to 20% merit early surgical management and as these are more serious, they present a high risk of subsequent complications. In this review, we present a case of tracheobronchial injury secondary to blunt chest trauma managed in the intensive care unit of our hospital that required early surgical correction and presented late complications that ultimately led to her death.

Indicaciones de broncoscopía flexible en pediatría

Desde la introducción de la Broncoscopía flexible (Fibrobroncoscopía) después de 1960, han habido relativamente, pocos avances tecnológicos en las tres décadas posteriores, pasando por el desarrollo de video broncoscopios de luz blanca hasta la introducción de un sistema electrónico de video llamado CCD e incluso la creación de broncoscopios flexibles híbridos que en conjunto con la adquisición de dispositivos auxiliares tales como (fórceps para biopsia, cepillos bronquiales) y técnicas especiales como (los aspirados bronquiales, lavados bronquiales y lavados broncoalveolares), además del entrenamiento de los neumólogos pediatras endoscopistas y anestesiólogos, se han ampliado grandemente las indicaciones para la realización de este procedimiento en pediatría. Esta revisión tiene como objetivo dar un panorama a los pediatras y médicos en general de la amplia variedad de indicaciones para la realización de este procedimiento en pediatría. Procedimiento considerado como una herramienta diagnóstica invaluable y un procedimiento muy seguro, con una morbilidad menor del 2,5% y mortalidad muy baja (

Since the introduction of the Flexible Bronchoscopy after 1960 , there have been relatively few technological advances in three decades , including the development of bronchoscopes video of white light until the introduction of an electronic video called CCD and even creation of flexible bronchoscopes hybrids in conjunction with the acquisition of auxiliary devices like (forceps biopsy , bronchial brushes) and special techniques such as (bronchial aspirates, bronchial washings and bronchoalveolar lavage), in addition to training of pediatricians and anesthesiologists, pulmonologists endoscopists have been greatly expanded the indications for performing this procedure in children. This review aims to give an overview to general pediatricians and the wide variety of indications for performing this procedure in children. Procedure considered an invaluable diagnostic tool and a very safe procedure with less morbidity and mortality of 2.5% very low (< 0.05% ). Even lower percentages except for transbronchial biopsy in children whose practice is deprecated because the sample obtained is very small to make an accurate diagnosis.

Neumotórax espontáneo primario recurrente

Presentamos un caso de neumotórax espontáneo primario recurrente en un adolescente de 13 años de edad previamente sano . El paciente presentó súbitamente dolor punzante en el hemitórax izquierdo y disnea de medianos y grandes esfuerzos. En la radiografía de tórax se evidenció un neumotórax izquierdo. El paciente fue referido al Hospital del Niño para su manejo. Se refiere un episodio similar al descrito seis meses antes del evento actual. Se encontraba asintomático al momento de su hospitalización. Era evidente una elevación anterior del hemitórax izquierdo y disminución de los ruidos pulmonares en el campo pulmonar izquierdo. En la radiografía de tórax se encontró un neumotórax izquierdo de 70% y una bula en el lóbulo superior izquierdo. Se consideró el diagnóstico de un neumotórax espontáneo primario izquierdo recurrente. Fue tratado con oxigeno húmedo al 100%, resección de las bulas y pleurodesis química. El centrol radiográfico mostró resolución del neumotórax. Egresó y continuo controles en la consulta de cirugía y neurología.

The authors describe a thirteen years old boy with a recurrence fo a primary spontaneous pneumothorax . He was a healthy boy without underlying lung disease. The main complain was the sudden onset of an acute sharp and diffuse pain located on the left hemithorax. Besides, the patient had medium and big efforts dyspnea. A chest radiograph was made and a left pneumothorax was detected. The patient was referred to the Hospital del Niño for his management and treatment. The patient had a history of a similar clinical picture six months before the actual event. The patient was asymptomatic at the moment of the hospital admission . Physical findings were asymmetry of the left hemithorax and diminished breath sounds on the affected side. There was evidence, on the chest radiograph, of a left pneumothorax of 70% with collapse of the lung and the presence of an apical sub pleural bulla in the upper left lobe. The diagnosis of a recurrence of a primary spontaneous pneumothorax was made by the patient´s history. The administration of humidified 100 per cent oxygen was indicated and the patient was evaluated by a surgeon for surgical treatment. The surgical procedure was resection of blebs by thoracoscopy and chemical pleurodesis. The control chest radiograph showed evacuation of the pneumothorax and reexpansion of the left lung. The chest tube was removed two days after surgery. The patient was discharged nine days after the hospital admission with follow up in the out patient clinic.

Detección del síndrome del virus del taura (TSV) en Litopenaeus vannamei (Boone) del occidente de Venezuela / Detection of taura syndrome virus in Litopenaeus vannamei (Boone) from western of Venezuela

El virus del Taura afecta a los cultivos de camarones peneidos ocasionando elevadas mortalidades reflejándose en la caída de la producción y elevando considerablemente los costos operacionales. En este trabajo, se describen los signos clínicos de la infección por el virus del síndrome de Taura (TSV) en granjas de cultivo comercial de Litopenaeus vannamei ubicadas en el occidente de Venezuela. Las muestras fueron tomadas de granjas afectadas y correspondieron a animales con signos clínicos muy conspicuos y de aquellos que habían superado la enfermedad. El TSV afectó a camarones juveniles, subadultos y adultos. Las granjas ubicadas en la costa del lago de Maracaibo fueron las más afectadas. Los casos agudos y crónicos mostraron esferoides típicos en el órgano linfoide. Los análisis por trascripción reversa de la reacción en cadena de la polimerasa (RT - PCR) confirmaron que los signos clínicos mostrados por los camarones afectados fueron debido a la infección con el virus del síndrome del Taura.

Taura syndrome virus considerably affects the cultures of peneid shrimp causing elevated mortalities, reflected on the decrease of the production and the increase the operational costs. This work describes the clinical signs of an infection with Taura Syndrome Virus on cultivated Litopenaeus vannamei in farms located in Western Venezuela. Shrimp samples with very conspicuous clinical signs and those that had overcome the illness were taken from affected farms. The effects of TSV were observed in juvenile, subadults and adult shrimp. The farms located off the coast of Maracaibo Lake were the most affected. The acute and chronic cases showed typical spheroids in the lymphoid organ. The RT-PCR analysis confirmed that the clinical signs shown by the affected shrimp were due to infection by the Taura virus.