First-line therapy with palbociclib in patients with advanced HR+/HER2- breast cancer: The real-life study PALBOSPAIN.

PURPOSE: To evaluate the efficacy and safety of first-line therapy with palbociclib in a Spanish cohort treated after palbociclib approval. METHODS: PALBOSPAIN is an observational, retrospective, multicenter study evaluating real-world patterns and outcomes with 1 L palbociclib in men and women (any menopausal status) with advanced HR+/HER2- BC diagnosed between November 2017 and November 2019. The primary endpoint was real-world progression-free survival (rw-PFS). Secondary endpoints included overall survival (OS), the real-world response rate (rw-RR), the clinical benefit rate, palbociclib dose reduction, and safety. RESULTS: A total of 762 patients were included. The median rw-PFS and OS were 24 months (95% CI 21-27) and 42 months (40-not estimable [NE]) in the whole population, respectively. By cohort, the median rw-PFS and OS were as follows: 28 (95% CI 23-39) and 44 (95% CI 38-NE) months in patients with de novo metastatic disease, 13 (95% CI 11-17) and 36 months (95% CI 31-41) in patients who experienced relapse < 12 months after the end of ET, and 31 months (95% CI 26-37) and not reached (NR) in patients who experienced relapse > 12 months after the end of ET. rw-PFS and OS were longer in patients with oligometastasis and only one metastatic site and those with non-visceral disease. The most frequent hematologic toxicity was neutropenia (72%; grade ≥ 3: 52.5%), and the most common non-hematologic adverse event was asthenia (38%). CONCLUSION: These findings, consistent with those from clinical trials, support use of palbociclib plus ET as 1 L for advanced BC in the real-world setting, including pre-menopausal women and men. TRIAL REGISTRATION NUMBER: NCT04874025 (PALBOSPAIN). Date of registration: 04/30/2021 retrospectively registered.

Dynamical effects on the O(3P) + D2 reaction and its impact on the Λ-doublet population.

The O(3P) + D2 → OD(2Π) + D reaction presents the peculiarity of taking place on two different potential energy surfaces (PESs) of different symmetry, 3A' and 3A'', which become degenerate for collinear configurations where the saddle-point of the reaction is located. The degeneracy is broken for non-collinear approaches with the energy on the 3A' PES rising more abruptly with the bending angle, making the frequency of this mode higher on the 3A' state. Consequently, the 3A' PES should be less reactive than the 3A'' one. Nevertheless, quantum scattering calculations show that the cross section is higher on the 3A' PES for energies close to the classical reaction threshold and rotationless reactant. It is found that the differences between the reactivity on the two PESs are greater for low values of total angular momentum, where the centrifugal barrier is lower and contribute to the higher population of the Π(A') Λ-doublet states of OD at low collision energies. At high collision energies, the Π(A') Λ-doublet state is also preferentially populated. Analysis of the differential cross sections reveals that the preponderance for the Π(A') Λ-doublet at low energies comes from backward scattering, originating from the reaction on the 3A' PES, while at high energies, it proceeds from a different mechanism that leads to sideways scattering on the 3A'' PES and that populates the Π(A') manifold.

Exact solution for the interaction of two decaying quantized fields.

We show that the Markovian dynamics of two coupled harmonic oscillators may be analyzed using a Schrödinger equation and an effective non-Hermitian Hamiltonian. This may be achieved by a non-unitary transformation that involves superoperators; such transformation enables the removal of quantum jump superoperators, which allows us to rewrite the Lindblad master equation in terms of a von Neumann-like equation with an effective non-Hermitian Hamiltonian. This may be generalized to an arbitrary number of interacting fields. Finally, by applying an extra non-unitary transformation, we may diagonalize the effective non-Hermitian Hamiltonian to obtain the evolution of any input state in a fully quantum domain.

Tumor fibroso pleural ¿son realmente benignos? ¿Cuándo deben operarse? / Pleural fibrous tumor, are they really benign? When should they have operation?

El tumor fibroso pleural es un tumor habitualmente asintomático, benigno y de lento crecimiento, que en un pequeño porcentaje de los casos tiene un comportamiento más agresivo. Para definir los criterios de malignidad es necesario un análisis inmunohistoquímico. El tratamiento de elección es la resección quirúrgica completa con márgenes de seguridad ya sea por toracotomía o por videotoracoscopia en función del tamaño. Se encuentra en estudio la utilización de terapia adyuvante radioterápica o quimioterápica que en el momento actual no cuenta con resultados significativos. Presentamos dos casos que fueron tratados de forma quirúrgica, con extirpación completa siendo el primero definido como maligno según los criterios histológicos y el segundo benigno, pero de alto riesgo. Solo uno de ellos recibió terapia adyuvante. (AU)

Solitary fibrous pleural tumor is a usually asymptomatic, benign and slow-growing tumor, which in a small percentage of cases has a more aggressive behavior. To define the malignancy criteria, an immunohistochemical analysis is necessary. The gold standard treatment is a complete surgical resection with safety margins either by thoracotomy or by videothoracoscopy depending on the size. The use of radiotherapy or chemotherapy as an adjuvant therapy is under study, which at the present time does not have significant results. We present two cases that were treated surgically, with complete removal, one being classified as malignant according to histological criteria and the other benign but high risk. Only one of them received adjuvant therapy. (AU)

Fallo ovárico, una problemática para las mujeres en edad reproductiva y su relación genética / Ovarian failure, a problem for women in reproductive age and its genetic relationship

La insuficiencia ovárica primaria es una condición en la que las mujeres menores de 40años experimentan oligomenorrea o amenorrea durante 4meses o más; esta pérdida temprana de la función ovárica puede estar relacionada con una serie de etiologías, incluidos trastornos genéticos, autoinmunes, infecciones o causas iatrogénicas; no obstante, del 74 al 90% son idiopáticas. A pesar de ser una alteración poco prevalente, es de gran importancia clínica, ya que afecta en múltiples aspectos de la vida a todas las mujeres. En la actualidad se están desarrollando diferentes estudios con el fin de encontrar nuevos blancos moleculares para establecer nuevas terapias para el tratamiento de esta patología.(AU)

Primary ovarian failure is a condition in which women under 40 experience oligomenorrhea or amenorrhea for 4months or longer; this early ovarian function loss may be related to a series of etiologies, including genetic disorders, autoimmune diseases, infections or iatrogenic causes; however 74%-90% are idiopathic. Despite being a less prevalent disorder, it is of great clinical importance since it affects all women in multiple aspects of life. At present, different studies are being developed in order to find new molecular targets to establish new therapies for the treatment of this pathology.(AU)

Experiencia de 20 años en el control de la hipertensión arterial en un centro de salud en España: control estricto versus no estricto / Twenty-year experience in strict versus non-strict control of arterial hypertension in a health center in Spain

Introducción y objetivos En los ensayos clínicos la reducción eficaz de la presión arterial (PA) produce una disminución de la incidencia de la morbimortalidad cardiovascular (CV). Nuestro objetivo principal es conocer si en las condiciones reales de la práctica clínica el control de la PA reduce a largo plazo los eventos CV. Pacientes y métodos El estudio se realizó en 164 pacientes con hipertensión arterial (HTA) elegidos entre los pacientes que acudían a las consultas de medicina de familia por HTA. Se hizo un análisis entre los pacientes que presentaban una PA clínica inferior a 140/90mmHg y los que la tenían más elevada. Los pacientes se seguían hasta que se producía un evento CV o hasta un máximo de 20 años, en que se finalizaba el seguimiento. Resultados Del total de los 164 pacientes alcanzaron un buen control clínico de la HTA 93 (56,7%) pacientes y no lo alcanzaron 71 (42,2%). En el análisis multivariante quedó únicamente como variable predictora de eventos CV la falta de control estricto de la HTA (HR: 2,93; IC 95%: 1,45-5,89; p=0,003), y el sexo femenino fue protector para eventos CV (HR: 0,37; IC 95%: 0,18-0,74; p=0,005) Conclusiones La variable predictora fundamental de morbimortalidad CV en pacientes con HTA es la falta de control estricto de la HTA; las mujeres también tuvieron menos complicaciones CV (AU)

Introduction and aims During clinical trials effective reduction of blood pressure (BP) leads to a reduction in the incidence of cardiovascular (CV) morbimortality. Our main aim is to ascertain whether, under actual conditions of clinical practice, BP monitoring leads to a long-term reduction in CV events. Patients and methods The study was performed on 164 patients with hypertension (HT) selected among patients who came to family medicine consultations because of HT. An analysis was performed between patients who presented clinical BP lower than 140/90mmHg and those that had higher levels. When patients entered the study, they were followed up until a CV event occurred or up to a maximum of 20 years, at which time follow up ended. Results Of the total of 164 patients, good control of BP was attained by 93 (56.7%), and 71 did not attain good control (42.2%). In the multivariate analysis, the only predictive variable for CV events was the lack of strict control of BP (HR: 2.93; 95% CI: 1.45-5.89; p=0.003), and the female sex was protective for CV events (HR: 0.37; 95% CI: 0.18-0.74; p=0.005). Conclusions The fundamental predictor variable of CV morbimortality in patients with HT is the lack of HT strict control; the women also had fewer CV complications (AU)

An Integrated Platform for in vivo Electrophysiology in Spatial Cognition Experiments.

Spatial cognition research requires behavioral paradigms that can distinguish between different navigational elements, such as allocentric (map-like) navigation and egocentric (e.g., body centered) navigation. To fill this need, we developed a flexible experimental platform that can be quickly modified without the need for significant changes to software and hardware. In this paper, we present this inexpensive and flexible behavioral platform paired with software which we are making freely available. Our behavioral platform serves as the foundation for a range of experiments, and though developed for assessing spatial cognition, it also has applications in the non-spatial domain of behavioral testing. There are two components of the software platform, 'Maze' and 'Stim Trigger'. Both programs can work in conjunction with electrophysiology acquisition systems, allowing for precise time stamping of neural events with behavior. The Maze program includes functionality for automatic reward delivery based on user defined zones. 'Stim Trigger' permits control of brain stimulation via any equipment that can be paired with an Arduino board. We seek to share our software and leverage the potential by expanding functionality in the future to meet the needs of a larger community of researchers.

Development, implementation and evaluation of a multinational FLS mentorship programme in Latin America.

Realising the benefits of systematic secondary fracture prevention requires supporting local sites to get started and becoming effective. We here describe the development, implementation and impact of a regional fracture liaison service (FLS) mentorship programme in Latin America that led to 64 FLS getting started and coverage of 17,205 patients. INTRODUCTION: Despite treatments and service models to deliver effective secondary fracture prevention, most patients are left untreated after a fragility fracture. To improve the capability to get FLS started and more effective, we describe the development, implementation and evaluation of an international programme to develop national communities of FLS mentors as part of the Capture the Fracture Partnership in Latin America. METHODS: The IOF regional team and the University of Oxford developed the curriculum and associated resources for training mentors in setting up FLS, service improvement and mentorship. Mentors were selected during a preparatory meeting, trained using live online sessions followed by regular mentor-led post-training meetings. The programme was evaluated using a pre-training needs assessment and post-training evaluation based on Moore's outcomes. RESULTS: The mentorship programme was initiated in Mexico, Brazil, Colombia and Argentina. The mentors were multidisciplinary, including orthopaedic surgery, rehabilitation, rheumatology, endocrinology, geriatrics, gynaecology and internal medicine. There was 100% participation in training sessions and reported satisfaction with the training. Since the initiation of the training programme, 22 FLS have been set up in Mexico, 30 in Brazil, 3 in Colombia and 9 in Argentina, in comparison with two in Chile and none in any other LATAM countries that were not involved in the mentorship programme. This equates to approximately 17,025 additional patients identified from 2019 to 2021 after initiation of mentorship. The mentors have engaged with 58 FLS for service development. Post-training activities include two published national best practice guidelines and other country-specific resources for FLS in the local language. CONCLUSION: Despite the COVID pandemic, the mentorship pillar of the Capture the Fracture Partnership has developed a community of FLS mentors with measurable improvement in national FLS provision. The programme is a potentially scalable platform to develop communities of mentors in other countries.

Supramolecular Block Copolymers from Tricarboxamides. Biasing Co-assembly by the Incorporation of Pyridine Rings.

The synthesis of a series of triangular-shaped tricarboxamides endowed with three picoline or nicotine units (compounds 2 and 3, respectively) or just one nicotine unit (compound 4) is reported, and their self-assembling features investigated. The pyridine rings make compounds 2-4 electronically complementary with our previously reported oligo(phenylene ethynylene)tricarboxamides (OPE-TA) 1 to form supramolecular copolymers. C3 -symmetric tricarboxamide 2 forms highly stable intramolecular five-membered pseudocycles that impede its supramolecular polymerization into poly-2 and the co-assembly with 1 to yield copolymer poly-1-co-2. On the other hand, C3 -symmetric tricarboxamide 3 readily forms poly-3 with great stability but unable to form helical supramolecular polymers despite the presence of the peripheral chiral side chains. The copolymer poly-1-co-3 can only be obtained by a previous complete disassembly of the constitutive homopolymers in CHCl3 . Helical poly-1-co-3 arises in a process involving the transfer of the helicity from racemic poly-1 to poly-3, and the amplification of asymmetry from chiral poly-3 to poly-1. Importantly, C2v -symmetric 4, endowed with only one nicotinamide moiety and three chiral side chains, self-assembles into a P-type helical supramolecular polymer (poly-4) in a thermodynamically controlled cooperative process. The combination of poly-1 and poly-4 generates chiral supramolecular copolymer poly-1-co-4, whose blocky microstructure has been investigated by applying the previously reported supramolecular copolymerization model.

[Twenty-year experience in strict versus non-strict control of arterial hypertension in a health center in Spain]. / Experiencia de 20 años en el control de la hipertensión arterial en un centro de salud en España: control estricto versus no estricto.

INTRODUCTION AND AIMS: During clinical trials effective reduction of blood pressure (BP) leads to a reduction in the incidence of cardiovascular (CV) morbimortality. Our main aim is to ascertain whether, under actual conditions of clinical practice, BP monitoring leads to a long-term reduction in CV events. PATIENTS AND METHODS: The study was performed on 164 patients with hypertension (HT) selected among patients who came to family medicine consultations because of HT. An analysis was performed between patients who presented clinical BP lower than 140/90mmHg and those that had higher levels. When patients entered the study, they were followed up until a CV event occurred or up to a maximum of 20 years, at which time follow up ended. RESULTS: Of the total of 164 patients, good control of BP was attained by 93 (56.7%), and 71 did not attain good control (42.2%). In the multivariate analysis, the only predictive variable for CV events was the lack of strict control of BP (HR: 2.93; 95% CI: 1.45-5.89; p=0.003), and the female sex was protective for CV events (HR: 0.37; 95% CI: 0.18-0.74; p=0.005). CONCLUSIONS: The fundamental predictor variable of CV morbimortality in patients with HT is the lack of HT strict control; the women also had fewer CV complications.

Influencia de la anhedonia en la evolución clínica del trastorno depresivo / Influence of anhedonia on the clinical course of depressive disorder

La anhedonia es la ausencia o capacidad reducida para experimentar placer. Es un síntoma importante en la depresión y un síntoma negativo de la esquizofrenia. Se presenta un estudio descriptivo prospectivo (diciembre 2018 a julio de 2020) con un seguimiento de seis meses, desarrollado en las Consultas Externas de Psiquiatría del Hospital Central de la Defensa Gómez Ulla. Para cuantificar la anhedonia se ha empleado la escala SHAPS y para el seguimiento de la clínica depresiva el cuestionario CET-DE. Se aplican también otras escalas como la escala CGI (impresión subjetiva gravedad/mejoría por parte del psiquiatra) y la EVA modificada (impresión subjetiva del paciente de su estado de gravedad). De 60 pacientes reclutados, 48 completaron el protocolo del estudio (2 visitas), siendo 60 % mujeres con una media de edad de 48 años. En la visita basal el porcentaje de anhedónicos fue del 67 %, de los cuales el 48 % fue considerado grave por parte del profesional sanitario. La presencia de anhedonia se relacionó con mayor puntuación en la escala CET-DE. Tras la intervención psicoterapéutica, en la visita final el porcentaje de anhedónicos fue del 29 % y se clasificaron como graves por parte del profesional sanitario un 25 % de los pacientes. La persistencia de anhedonia en la visita final fue un factor de mala evolución clínica, pudiendo concluir que es un componente de la sintomatología residual de la depresión y un indicador de mal pronóstico. (AU)

Anhedonia is the absence or reduced ability to experience pleasure. It is a major symptom of depression and a negative symptom of schizophrenia. We present a prospective descriptive study (December 2018 to July 2020) with a 6-month follow-up, developed in the Psychiatric Outpatient Clinic of the “Hospital Central de la Defensa, Gómez Ulla”. The SHAPS scale was used to quantify anhedonia and the CET-DE questionnaire was used to monitor clinical depression. Other scales such as the CGI scale (subjective impression of severity/improvement was use by the psychiatrist) and the modified VAS (patient’s subjective impression of his or her state of severity) were also applied. Out of 60 patients recruited, 48 completed the study protocol (2 visits), 60 % were women with a mean age of 48 years. At the firts visit the percentage of anhedonia was 67 %, with 48 % considered severe by the physician. The presence of anhedonia was related to a higher score on the CET-DE scale. After the psychotherapeutic intervention, the percentage of anhedonia at the last visit was 29% in general and 25% of patients were classified as severe by the health professional. The persistence of anhedonia at the final visit was a factor of poor clinical evolution and we can conclude that it is a component of the residual symptomatology of depression and an indicator of poor prognosis. (AU)

Influencia de la anhedonia en la evolución clínica del trastorno depresivo / Influence of anhedonia on the clinical course of depressive disorder

La anhedonia es la ausencia o capacidad reducida para experimentar placer. Es un síntoma importante en la depresión y un síntoma negativo de la esquizofrenia. Se presenta un estudio descriptivo prospectivo (diciembre 2018 a julio de 2020) con un seguimiento de seis meses, desarrollado en las Consultas Externas de Psiquiatría del Hospital Central de la Defensa Gómez Ulla. Para cuantificar la anhedonia se ha empleado la escala SHAPS y para el seguimiento de la clínica depresiva el cuestionario CET-DE. Se aplican también otras escalas como la escala CGI (impresión subjetiva gravedad/mejoría por parte del psiquiatra) y la EVA modificada (impresión subjetiva del paciente de su estado de gravedad). De 60 pacientes reclutados, 48 completaron el protocolo del estudio (2 visitas), siendo 60 % mujeres con una media de edad de 48 años. En la visita basal el porcentaje de anhedónicos fue del 67 %, de los cuales el 48 % fue considerado grave por parte del profesional sanitario. La presencia de anhedonia se relacionó con mayor puntuación en la escala CET-DE. Tras la intervención psicoterapéutica, en la visita final el porcentaje de anhedónicos fue del 29 % y se clasificaron como graves por parte del profesional sanitario un 25 % de los pacientes. La persistencia de anhedonia en la visita final fue un factor de mala evolución clínica, pudiendo concluir que es un componente de la sintomatología residual de la depresión y un indicador de mal pronóstico. (AU)

Anhedonia is the absence or reduced ability to experience pleasure. It is a major symptom of depression and a negative symptom of schizophrenia. We present a prospective descriptive study (December 2018 to July 2020) with a 6-month follow-up, developed in the Psychiatric Outpatient Clinic of the “Hospital Central de la Defensa, Gómez Ulla”. The SHAPS scale was used to quantify anhedonia and the CET-DE questionnaire was used to monitor clinical depression. Other scales such as the CGI scale (subjective impression of severity/improvement was use by the psychiatrist) and the modified VAS (patient’s subjective impression of his or her state of severity) were also applied. Out of 60 patients recruited, 48 completed the study protocol (2 visits), 60 % were women with a mean age of 48 years. At the firts visit the percentage of anhedonia was 67 %, with 48 % considered severe by the physician. The presence of anhedonia was related to a higher score on the CET-DE scale. After the psychotherapeutic intervention, the percentage of anhedonia at the last visit was 29% in general and 25% of patients were classified as severe by the health professional. The persistence of anhedonia at the final visit was a factor of poor clinical evolution and we can conclude that it is a component of the residual symptomatology of depression and an indicator of poor prognosis. (AU)

Diagnóstico y evolución de los pacientes con derrames pleurales idiopáticos / Diagnosis and outcome of patients with idiopathic pleural effusions

Introducción No se ha determinado la evolución de los pacientes con derrames pleurales idiopáticos con un seguimiento a largo plazo. Métodos Entre octubre de 2013 y junio de 2021 se hizo un seguimiento prospectivo de todos los pacientes con derrame idiopático mediante exploración clínica y estudios de imagen al cabo de 1, 3 y seis meses y cada seis meses durante un mínimo de un año. Resultados Veintinueve pacientes fueron diagnosticados de derrame idiopático y objeto de seguimiento. Durante el seguimiento se detectó un mesotelioma en dos pacientes al cabo de siete y 18 meses; en uno de ellos se observó líquido pleural teñido de sangre y el otro refirió una pérdida de peso de 10%. En ninguno de los pacientes con derrame que cubriera menos de dos tercios del hemitórax y sin síntomas constitucionales ni aparición de líquido teñido de sangre se diagnosticó un mesotelioma. La mayoría de los derrames desaparecieron o mostraron una clara mejoría en los primeros seis meses. Conclusiones Los pacientes sin pérdida de peso y con derrames no hemáticos pequeños pueden beneficiarse de un tratamiento conservador y un seguimiento clínico-radiológico (AU)

Introduction Long-term follow-up course for patients with idiopathic pleural effusions has not been established. Methods From October 2013 to June 2021 all patients with idiopathic effusion were prospectively followed up with clinical examination and imaging at 1,3,6 and every 6 months for a minimum of 1 year. Results Twenty-nine patients were diagnosed with idiopathic effusion and followed up. Mesothelioma was detected during the follow-up in two patients at 7 and 18 months, one of whom had blood-tinged pleural fluid and the other reported a 10% weight loss. Mesothelioma was not diagnosed in any of the patients with effusion covering less than two thirds of the hemithorax, and without constitutional symptoms or a blood-tinged fluid appearance. Most of the effusions resolved or showed a clear improvement in the first six months. Conclusions Patients without weight loss and with small, non-hematic effusions, may benefit from conservative treatment and clinical-radiological follow-up (AU)