Treatment with fostamatinib in patients with immune thrombocytopenia: Experience from the Andalusian region in Spain-The Fostasur Study.

Immune thrombocytopenia (ITP) is characterized by low platelet counts (PLTs) and an increased risk of bleeding. Fostamatinib, a spleen tyrosine kinase inhibitor, has been approved as a second-line treatment for ITP. Real-world data on fostamatinib are lacking. This observational, retrospective, multicentre study, conducted in the Andalusia region of Spain, evaluated 44 adult primary ITP patients (47.7% female; median age 58 years; newly diagnosed ITP 6.8%; persistent 13.6%; chronic 79.5%; median four prior treatments) after ≥ 4 weeks of fostamatinib therapy. The median PLT at the initiation of fostamatinib was 15 × 109/L. Common reasons for starting fostamatinib were refractoriness or intolerance to prior therapy, oral medication preference, history of thrombosis and cardiovascular risk. Dosing was individualized based on efficacy and tolerance. After 2 weeks, global response rate was 56.8% (response and complete response). Response rates were 70.5%, 62.5% and 64% at 4 weeks, 12 weeks and at the end of the study respectively. Adverse events were mild, and no patients discontinued as a result. This real-world study demonstrated a response rate similar to fostamatinib as seen in the pivotal clinical trials while including newly diagnosed patients and allowing for individualized dosing.

Outpatient antipsychotic use and severe COVID-19: avoiding the impact of age in a real-world data study.

BACKGROUND: The association between use of antipsychotics and COVID-19 outcomes is inconsistent, which may be linked to use of these drugs in age-related diseases. Furthermore, there is little evidence as regards their effect in the non-geriatric population . We aim to assess the association between antipsychotic use and risk of disease progression and hospitalisation due to COVID-19 among the general population, stratifying by age. METHODS: We conducted a population-based, multiple case-control study to assess: (1) risk of hospitalisation, with cases being patients with a PCR(+)test who required hospitalisation and controls being subjects without a PCR(+) test; and (2) risk of progression to hospitalisation, with cases being the same as those used in the hospitalisation substudy and controls being non-hospitalised PCR(+) patients. We calculated adjusted odds-ratios (aOR) and 95% confidence intervals (CI), both overall and stratified by age. RESULTS: Antipsychotic treatment in patients <65 years was not associated with a higher risk of hospitalisation due to COVID-19 (aOR 0.94 [95%CI 0.69-1.27]) and disease progression among PCR(+) patients (aOR 0.96 [95%CI 0.70-1.33]). For patients aged ≥65 years, however, there was a significant, increased risk of hospitalisation (aOR 1.58 [95%CI 1.38-1.80]) and disease progression (aOR 1.31 [95%CI 1.12-1.55]). CONCLUSIONS: The results of our large-scale real world data study suggest that antipsychotic use is not associated with a greater risk of hospitalisation due to COVID-19 and progression to hospitalisation among patients younger than 65 years. The effect found in the over-65-year age group might be associated with off-label use of antipsychotics.

Impact of prior antihypertensive treatment on COVID-19 outcomes, by active ingredient.

OBJECTIVES: To assess the impact of prior chronic treatment with angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin-receptor blockers (ARBs), both as a group and by active ingredient, on severity (risk of hospitalization and mortality), progression of and susceptibility to COVID-19. METHODS: We conducted a multiple population-based case-control study in Galicia (north-west Spain). The study data were sourced from medical, administrative and clinical databases. We assessed: (1) risk of hospitalization, by selecting all patients hospitalized due to COVID-19 with PCR + as cases, and a random sample of subjects without a PCR + as controls; (2) COVID-19 mortality risk; (3) risk of disease progression; and (4) susceptibility to SARS-CoV-2, considering all patients with PCR + as cases, and the same subjects used in the previous model as controls. Adjusted odds ratios (aORs) were calculated. RESULTS: ACEIs and ARBs were shown to decrease the risk of hospitalization (aOR = 0.78 [95%CI 0.69-0.89] and aOR = 0.80 [95%CI 0.72-0.90] respectively), risk of mortality (aOR = 0.71 [95%CI 0.52-0.98] and aOR = 0.69 [95%CI 0.52-0.91] respectively), and susceptibility to the virus (aOR = 0.88 [95%CI 0.82-0.94] and aOR = 0.92 [95%CI 0.86-0.97] respectively). By active ingredient: use of enalapril was associated with a significantly lower risk of hospitalization (aOR = 0.72 [95%CI 0.61-0.85]), mortality (aOR = 0.59 [95%CI 0.38-0.92]) and susceptibility to COVID-19 (aOR = 0.86 [95%CI 0.79-0.94]); and use of candesartan was associated with a decreased risk of hospitalization (aOR = 0.76 [95%CI 0.60-0.95]), mortality (aOR = 0.36 [95%CI 0.17-0.75]) and disease progression (aOR = 0.73 [95%CI 0.56-0.95]). CONCLUSION: This large-scale real-world data study suggest that enalapril and candesartan are associated with a considerable reduction in risk of severe COVID19 outcomes.

Analysis of correlation of pre-therapeutic assessment and the final diagnosis in endometrial cancer: role of tumor volume in the magnetic resonance imaging.

Objective: To evaluate whether the introduction of tumor volume as new parameter in the MRI assessment could improve both concordance between preoperative and postoperative staging, and the identification of histological findings. Methods: A retrospective observational study with 127 patients with endometrial cancer (EC) identified between 2016 and 2021 at the Juan Ramon Jimenez University Hospital, Huelva (Spain) was carried out. Tumor volume was measured in three ways. Analyses of Receiver Operating Characteristic (ROC) curve and the area under the curve (AUC) were performed. Results: Although preoperative MRI had an 89.6% and 66.7% sensitivity for the detection of deep mucosal invasion and cervical stroma infiltration, preoperative assessment had an intraclass correlation coefficient of 0.517, underestimating tumor final stage in 12.6% of cases, with a poor agreement between preoperative MRI and postoperative staging (κ=0.082) and low sensitivity (14.3%) for serosa infiltration. The cut-off values for all three volume parameters had good/excellent AUC (0.73-0.85), with high sensitivity (70-83%) and specificity (64-84%) values for all histopathological variables. Excellent/good agreement was found all volume parameters for the identification of deep myometrial invasion (0.71), cervical stroma infiltration (0.80), serosa infiltration (0.81), and lymph node metastases (0.81). Conclusion: Tumor volume measurements have good predictive capacity to detect histopathological findings that affect final tumor staging and might play a crucial role in the preoperative assessment of patients with endometrial cancer in the future.

Role of tumor volume in endometrial cancer: An imaging analysis and prognosis significance.

OBJECTIVE: To evaluate the prognostic value of tumor volume on preoperative MRI in endometrial cancer (EC) patients and its association with adverse prognostic factors and survival. METHODS: A retrospective observational study with 127 consecutive patients with endometrioid EC was carried out between 2016 and 2021 at Juan Ramón Jiménez University Hospital, Huelva (Spain). All patients underwent preoperative magnetic resonance imaging (MRI) for local staging. The tumor volume was analyzed on MRI by two different methods: by measuring the three maximum diameters of the tumor according to an ellipse formula and by manual region of interest in different sections; the ratio between tumor volume and uterus volume was also calculated as a third tool. The relationships between volume, prognostic factors, and survival were analyzed. RESULTS: A total of 127 patients with endometroid EC underwent preoperative MRI and were included in the study. Tumor volume was significantly higher for deep myometrial invasion, cervical stromal involvement, infiltrated serosa, lymph node metastases, high-grade EC, and lymphovascular space involvement, advanced FIGO stage, and High Recurrence Risk Group (P < 0.001). ROC curves showed that tumor volume greater than 25 cm3 predicts lymph node metastases. Volume index greater than 17 cm3 was associated with reduced disease-free survival (P < 0.001) and overall survival (P < 0.003). Multivariate analysis showed that the greatest tumor volume had an independent impact on recurrence (odds ratio [OR]1.019, 95% confidence interval [CI] 1.005-1.032) and survival (OR 1.027, 95% CI 1.009-1.046). CONCLUSIONS: This study shows an important correlation between tumor volume on MRI and poor prognostic factors. Preoperative tumor volume on MRI is a valuable biomarker to be considered for management of EC.

Características clínicas, pronóstico y factores asociados de la bacteriemia por Staphylococcus aureus en la actualidad / Clinical characteristics and prognosis of Staphylococcus aureus bacteremia

Introducción. Describimos las características de los pacientes con bacteriemia por Staphylococcus aureus en un hospital de tercer nivel y analizamos sus complicaciones, la mortalidad y los factores asociados a las mismas. Métodos. Se analizaron de manera retrospectiva los datos de los pacientes ingresados con bacteriemia por S. aureus entre marzo de 2020 y febrero de 2021 en el hospital universitario Miguel Servet de Zaragoza. Resultados. La mortalidad a los 14 días fue del 24,2% y la mortalidad a los 30 días del 40%. La aparición de complicaciones [HR 3,1 (1,2-8,05)] y la edad >65 años [HR 3,1 (IC95% 1,4-6,6)] disminuyeron la supervivencia global de manera significativa. En la regresión logística se asociaron a mayor mortalidad a los 30 días la edad >65 años [OR 6,3 (IC95% 1,7-23,1)], la presencia de sepsis [OR 19,3 (IC95% 5,4-68,7)] y solo con cierta tendencia, el número de frascos de HC (+) ≥3 [OR 5,4 (IC95% 0,8-34,1)]. Se asoció a mayor mortalidad a los 14 días el haber presentado sepsis [OR 58,2 (IC95% 5,7-592,9)], el número frascos de HC (+) ≥3 [OR 14,1 (IC95% 1,1-173,7)] y una edad >65 años [OR 1,1 (IC95% 1,03-1,1) años]. Cuando analizamos juntos aquellos con un TP ≤12 horas y un número frascos de HC (+) ≥3, la sepsis fue más frecuente [30 pacientes (66,6%) vs 15 pacientes (33,3%); OR 3,4 (IC95% 1,5-8)]. Conclusiones. La mortalidad a los 14 y a los 30 días fue elevada, observándose una peor evolución en los pacientes con mayor edad, presencia de sepsis, un mayor número de frascos de hemocultivos positivos y un tiempo hasta hemocultivos positivos ≤12 h. (AU)

Introduction. Staphylococcus aureus bacteremia patients characteristics at a tertiary hospital are described, and complications, mortality and associated factors are analyzed. Methods. Data from patients with S. aureus bacteremia admitted between March 2020 and February2021 at Miguel Servet university hospital in Zaragoza were retrospectively analyzed. Results. Results showed a 14 days mortality of 24.2% and an 30 days mortality of 40%. Overall survival decreased with complications appearance [HR 3.1 (1.2-8.05)] and age over 65 years [HR 3.1 (1.4-6.6)]. The adjusted analysis showed correlation between a higher mortality at 14 and 30 days with age over 65 years [OR 6.3 (1.7-23.1)], sepsis presence [OR 19.3 (5.4-68.7)] and number of positive (+) blood cultures ≥3 [OR 5.4 (0.8-34.1)]. Mortality at 14 days was associated with sepsis presence [OR 58.2 (5.7-592.9)], number of positive (+) blood cultures ≥3 [OR 14.1 (1.1-173.7)] and an older age [OR 1.1 (1.03-1.1)]. Analyzing time to positive blood cultures ≤12 hours and number of positive blood cultures ≥ 3 at the same time, frequency of sepsis increased [30 patients (66.6%) vs 15 patients (33.3%); OR 3.4 (IC95% 1.5-8)]. Conclusions. High 14- and 30-days mortality were found, as well as a worse evolution in older age patients, with sepsis presence, and with greater number of positive blood cultures and times to positive blood cultures ≤12 h. (AU)

Understanding Primary Care Physician Vaccination Behaviour: A Systematic Review.

BACKGROUND: Vaccine hesitancy decreases adult vaccination coverage and has been recognized by WHO as a major health threat. Primary care physicians (PCP) play a key role in vaccination by giving vaccine counselling to their patients. The aim of this systematic review is to identify the knowledge, beliefs, attitudes and barriers (KBAB) associated with own vaccination and patient recommendation in primary care physicians. METHODS: MEDLINE/PubMed, EMBASE and Cochrane Library databases were used to search and identify relevant studies based on their title and abstract. In the next step, the full text of each previously selected article was read for eligibility. Articles were selected by two independent reviewers and data extraction was performed using tables. The following information was extracted: methodological characteristics, demographic factors, professional characteristics, and intrinsic or extrinsic factors influencing vaccination or recommendation. RESULTS: Our search yielded 41 eligible papers, data-sources, previous practices, belief in the effectiveness or safety of the vaccine, perceived risk, and trust in health authorities were all shown to be related to own vaccination and patient recommendation. CONCLUSION: Internet is the main source of information for PCP related to vaccine hesitancy. It is therefore essential to increase the presence and access to pro-vaccination content in this area. In addition, involving PCP in the establishment of vaccination recommendations could improve their credibility in the institutions. On the other hand, training in communication skills and establishing reminder systems could reflect higher vaccination coverage among their patients.

Impacto de la bacteriemia por Staphylococcus aureus en pacientes con COVID-19 / Impact of Staphylococcus aureus bacteremia in COVID-19 patients

Introducción. La enfermedad causada por SARS-CoV-2 (COVID-19) ha supuesto un desafío para los profesionales sanitarios desde su aparición. Staphylococcus aureus es uno de los principales patógenos causantes de infecciones bacterianas en pandemias virales. Sin embargo, se debe estudiar bien la co-infección por S. aureus causante de bacteriemia en pacientes con COVID-19. Métodos. Se analizaron los casos de bacteriemia por S. aureus (BSA) atendidos en el Hospital Miguel Servet (Zaragoza) desde marzo de 2020 hasta febrero de 2021. Se compararon las características clínicas, los factores de riesgo y mortalidad de los pacientes con BSA asociada a COVID-19 respecto los pacientes no-COVID-19. Resultados. Se identificaron 95 pacientes con BSA. El 27,3% fueron COVID-19 positivos. La BSA representó el 9,9% de las bacteriemias, siendo el segundo microorganismo en frecuencia tras E. coli. La bacteriemia nosocomial fue más frecuente en el grupo de pacientes con COVID-19. La fuente de BSA fue desconocida en el 46,2% de los pacientes con COVID-19. La fuente de BSA más frecuente en estos pacientes fue la respiratoria (26,9% vs 0%; P<0,001) seguida de la cutánea (15,5% vs 15,9%; P=1). El desarrollo de sepsis fue más frecuente en los pacientes con COVID-19 (61,5% vs 7,8%; P=0,336) y de ellos, los que recibieron dosis de dexametasona >6 mg/día (62,5% vs 37,5%; P< 0,05). Conclusiones. Nuestros datos sugieren que la BSA influye negativamente en la evolución de los pacientes con COVID-19. Sin embargo, se requieren más estudios y preferiblemente prospectivos para obtener datos sólidos sobre el impacto de la BSA en los pacientes con coronavirus. (AU)

Introduction. The disease caused by SARS-CoV-2 (COVID-19) has been a challenge for healthcare professionals since its appearance. Staphylococcus aureus has been described as one of the main pathogens causing bacterial infections in viral pandemics. However, co- infection with S. aureus causing bacteremia in patients with COVID-19 has yet to be well studied. Methods. We performed a e study of S. aureus bacteremia (SAB) at Hospital Miguel Servet (Zaragoza) from March 2020 to February 2021. The clinical characteristics, mortality and risk factors of adults hospitalized patients with BSA associated COVID-19 compared to patients without COVID-19. Results. A total of 95 patients with SAB were identified. 27.3% were positive for SARS-CoV-2. SAB represented 9.9% of bacteremia, being the second agent in frequency after E. coli. Nosocomial bacteremia was more frequent in the group of COVID-19 patients. The most frequent source of BSA in these patients was the respiratory source (26.9% vs 0%; P<0.001) followed by the skin (15.5% vs 15.9%; P=1). The development of sepsis was more frequent in COVID-19 patients (61,5% vs 7,8%; P=0,336) and among them, who received dexamethasone at doses > 6 mg/day (62.5% vs. 37.5%, P<0.05). Conclusions. Our data suggest that BSA has a negative impact on the evolution of patients with COVID-19. However, further and preferably prospective studies are required to obtain solid data on the impact of BSA on coronavirus patients. (AU)

Biochemical changes in the cytoplasm of bovine oocytes during the in vitro maturation process: a Raman microscopy study.

The sequence and chronology of the main biochemical changes occurring in the cytoplasm of bovine oocytes during the in vitro maturation process were tracked by Raman microscopy applied to cells previously subjected to enzymatic digestion of the zona pellucida. Specific spectral markers for proteins, lipids and carbohydrates were used to evaluate the developmental status of the ooplasm at four different times. Spectral changes revealed that lipid accumulation was dominant during the first six hours of culture while protein content reached the average levels characteristic of mature oocytes within the last four hours of the maturation process. A time-dependent decrease in carbohydrates was also observed. Finally, the carbohydrate-to-protein (P1037/P1002) ratio proved to be sensitive enough to determine the cytoplasmic maturation state of bovine oocytes and promises to be useful in future research aimed at optimizing culture conditions through the promotion of protein accumulation in the ooplasm.

Sistema web para la gestión de los enlaces de conectividad en el nodo Infomed de Villa Clara, Cuba / Connectivity Links Management Web System in the Infomed Node of Villa Clara, Cuba

La red Infomed se creó en Cuba para proporcionar el acceso a la información y el conocimiento a las personas e instituciones de la Salud Pública. La red posee un grupo de productos y servicios desplegados en las redes de nodos territoriales a lo largo del país. El Nodo provincial de Infomed de Villa Clara tiene dentro de sus funciones la gestión de los enlaces de conectividad para todas las instituciones de la provincia. En este proceso se identificaron problemáticas que evidencian que el mecanismo utilizado para la solicitud y procesamiento de los enlaces de conectividad no es eficiente, lo cual genera errores en los datos, duplicidad de información, así como una gestión lenta sujeta a vulnerabilidades. La presente investigación propone la solución a la problemática planteada a partir del desarrollo de una aplicación web para la gestión de los enlaces de conectividad que proporcione la optimización de la gestión de la información. Para la implementación de la aplicación se utilizó la metodología de desarrollo de software OpenUP. Se seleccionó el framework de desarrollo de software Django para la realización de la aplicación web con Python en la lógica de servidor. Como motor de la base de datos se empleó Mariadb, sobre un sistema operativo Linux en un entorno de virtualización utilizando Proxmox. Para la validación de la investigación se realizaron pruebas de funcionalidad(AU)

To provide access to information and knowledge for people and Public Health institutions, the Infomed network was created in Cuba. The network has a group of products and services deployed in the territorial node networks throughout the country. Within its functions, the Infomed Provincial Node of Villa Clara manages the connectivity links for all the institutions of the province, problems were identified in this area showing that the mechanism used for the request and processing of the connectivity links is not efficient, generating errors in the data, duplication of information, as well as a slow management and vulnerabilities. This research proposes the solution to the problem providing the development of a web application that makes optimal information management of connectivity. For the implementation of the application, the OpenUP software development methodology was used. The Django software development framework was selected for the realization of the web application with Python in the server logic. Mariadb was used as the database engine, on a Linux operating system in a virtualization environment using Proxmox. For the validation of the research, functionality tests were carried out(AU)

Development and Pilot Implementation of the Genomic Risk Assessment for Cancer Implementation and Sustainment (GRACIAS) Intervention in Mexico.

PURPOSE: Genomic cancer risk assessment (GCRA) is standard-of-care practice that uses genomic tools to identify individuals with increased cancer risk, enabling screening for early detection and cancer prevention interventions. GCRA is not available in most of Mexico, where breast cancer (BC) is the leading cause of cancer death and ovarian cancer has a high mortality rate. METHODS: Guided by an implementation science framework, we piloted the Genomic Risk Assessment for Cancer Implementation and Sustainment (GRACIAS) intervention, combining GCRA training, practice support, and low-cost BRCA1/2 (BRCA) gene testing at four centers in Mexico. The RE-AIM model was adapted to evaluate GRACIAS intervention outcomes, including reach, the proportion of new patients meeting adapted National Comprehensive Cancer Network criteria who participated in GCRA. Barriers to GCRA were identified through roundtable sessions and semistructured interviews. RESULTS: Eleven clinicians were trained across four sites. Mean pre-post knowledge score increased from 60% to 67.2% (range 53%-86%). GCRA self-efficacy scores increased by 31% (95% CI, 6.47 to 55.54; P = .02). Participant feedback recommended Spanish content to improve learning. GRACIAS promoted reach at all sites: 77% in Universidad de Guadalajara, 86% in Instituto Nacional de Cancerología, 90% in Tecnológico de Monterrey, and 77% in Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán. Overall, a pathogenic BRCA variant was identified in 15.6% (195 of 1,253) of patients. All trainees continue to provide GCRA and address barriers to care. CONCLUSION: We describe the first project to use implementation science methods to develop and deliver an innovative multicomponent implementation intervention, combining low-cost BRCA testing, comprehensive GCRA training, and practice support in Mexico. Scale-up of the GRACIAS intervention will promote risk-appropriate care, cancer prevention, and reduction in related mortality.

Experimental and theoretical vibrational study of the fungicide pyraclostrobin.

The vibrational study of the pyraclostrobin (methyl N-(2-{[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxymethyl}phenyl) N-methoxycarbamate) molecule, a synthetic fungicide for agricultural uses, was performed. Pyraclostrobin belongs to the strobilurin family and acts by inhibiting the fungus respiratory chain at the level of Complex III, becoming an excellent agent for preventive, curative and eradicative activities against a wide range of fungal plant pathogens. However, its presence needs to be monitored to avoid the excessive and/or improper use that may compromise human or environmental health. The FTIR and Raman spectra of pyraclostrobin in pure solid state were recorded and compared with those obtained from both the substance in CH2Cl2 solution and in an agricultural commercial product (Comet® BASF). The spectral analysis was complemented with quantum-chemical calculations at the DFT level (B3LYP/6-311G*) for the predictions of the molecular geometry and its vibrational behavior. The high flexibility of the molecule was explored by performing potential energy scans on several dihedral angles and the results suggested that the main conformer of pyraclostrobin is that possessing the ortho-substituted benzene ring in perpendicular orientation regarding the plane that contains the ether group and the pyrazole ring, although the presence of a second preferred conformation in the experimental vibrational spectra was not ruled out. Among the many vibrational bands of pyraclostrobin that were well identified in the spectrum of the composite product for agricultural use, the one located at 936 cm-1 stood out. This signal was assigned to a vibration of the pyrazole ring and promised to be a good candidate as marker of the presence of the fungicide in complex matrixes.

Subspecialty training in Europe: a report by the European Network of Young Gynaecological Oncologists.

BACKGROUND: ESGO (European Society of Gynaecological Oncology) and partners are continually improving the developmental opportunities for gynaecological oncology fellows. The objectives of this survey were to evaluate the progress in the infrastructure of the training systems in Europe over the past decade. We also evaluated training and assessment techniques, the perceived relevance of ENYGO (European Network of Young Gynaecological Oncologists) initiatives, and unmet needs of trainees. METHODOLOGY: National representatives of ENYGO from 39 countries were contacted with an electronic survey. A graduation in well/moderately/loosely-structured training systems was performed. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher's exact test, were used. RESULTS: National representatives from 33 countries answered our survey questionnaire, yielding a response rate of 85%. A national fellowship is offered in 22 countries (66.7%). A logbook to document progress during training is mandatory in 24 (72.7%) countries. A logbook of experience is only utilized in a minority of nations (18%) for assessment purposes. In 42.4% of countries, objective assessments are recognized. Trainees in most countries (22 (66.7%)) requested additional training in advanced laparoscopic surgery. 13 (39.4%) countries have a loosely-structured training system, 11 (33.3%) a moderately-structured training system, and 9 (27.3%) a well-structured training system. CONCLUSION: Since the last publication in 2011, ENYGO was able to implement new activities, workshops, and online education to support training of gynaecological oncology fellows, which were all rated by the respondents as highly useful. This survey also reveals the limitations in establishing more accredited centers, centralized cancer care, and the lack of laparoscopic training.

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-ß and PD-L1, in Second-Line Treatment of Patients With NSCLC: Results From an Expansion Cohort of a Phase 1 Trial.

INTRODUCTION: The safety and efficacy of bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of the transforming growth factor ß (TGF-ß) receptor II (a TGF-ß "trap") fused to a human immunoglobulin G1 antibody blocking programmed death-ligand 1 (PD-L1), was evaluated in patients with advanced NSCLC. METHODS: This expansion cohort of NCT02517398, an ongoing, phase 1, open-label trial, includes 80 patients with advanced NSCLC that progressed after platinum doublet therapy or after platinum-based adjuvant or neoadjuvant treatment and those who also have not received previous immunotherapy. Patients were randomized at a one-to-one ratio to receive either bintrafusp alfa 500 mg or the recommended phase 2 dosage of 1200 mg every 2 weeks. The primary end point was the best overall response (by Response Evaluation Criteria in Solid Tumors 1.1 as adjudicated by independent review committee) and was assessed by the objective response rate (ORR). RESULTS: A total of 80 patients were randomized to receive bintrafusp alfa 500 or 1200 mg (n = 40 each). Median follow-up was 51.9 weeks (IQR, 19.6-74.0). The ORR in all patients was 21.3% (17 of 80). The ORR was 17.5% (seven of 40) and 25.0% (10 of 40) for the 500 mg dose and the 1200 mg dose (recommended phase 2 dose), respectively. At the 1200 mg dose, patients with PD-L1-positive and PD-L1-high (≥80% expression on tumor cells) had ORRs of 36.0% (10 of 27) and 85.7% (six of seven), respectively. Treatment-related adverse events occurred in 55 of the 80 patients (69%) and were graded as greater than or equal to 3 in 23 of the 80 patients (29%). Of the 80 patients, eight (10%) had a treatment-related adverse event that led to treatment discontinuation; no treatment-related deaths occurred. CONCLUSIONS: Bintrafusp alfa had encouraging efficacy and manageable tolerability in patients with NSCLC previously treated with platinum.

Fabrication and Characterization of Hollow Microcapsules from Polyelectrolytes Bearing Thymine Pendant Groups for Ultraviolet-B (UVB)-Induced Crosslinking.

DNA - bioinspired polyelectrolytes poly[vinylbenzylthymine (VBT)-4-vinylbenzyltriethylammonium chloride (VBA)] and poly[vinylbenzylthymine (VBT)-4-vinylphenylsufonate (VPS)] were used for the preparation of hollow microcapsules (HMC) using the layer-by-layer method and CaCO3 microspheres as removable molds. Stable aqueous suspensions of spherical-shaped HMCs with a shell composed of six layers of VBA-based polyelectrolytes were obtained, of approximately (7.0±1.5) µm diameter and a shell thickness of 1 µm. Ultraviolet-B irradiation of the HMC suspensions induces an efficient crosslinking between adjacent polyelectrolyte chains through the formation of thymine photodimers, such as the cyclobutane pyrimidine dimer (CPD) and the (6-4) pyrimidine-pyrimidone photoproduct (6-4PP). This process resulted in a reduction of the average interstitial mesh size of the HMC shells, modulating their permeability properties and increasing the mechanical stability of the HMC without a noticeable modification of size and shape. Thus, the DNA-bioinspired polyelectrolytes are promising materials for the preparation of UVB-responsive HMCs.

Prevalencia de patología endometrial detectada por histeroscopia en un centro de tercer nivel / Prevalence of endometrial pathology by hysteroscopy among infertile patients in a tertiary referral hospital

Resumen OBJETIVO: Describir la prevalencia de patología endometrial diagnosticada mediante histeroscopia en pacientes infértiles atendidas en un centro de tercer nivel. MATERIALES Y MÉTODOS: Estudio descriptivo, retrospectivo y observacional efectuado en pacientes con diagnóstico de infertilidad atendidas en el Departamento de Biología de la Reproducción Humana del Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Ciudad de México. Criterios de inclusión: pacientes infértiles entre 18 y 43 años a quienes se realizó histeroscopia. Criterios de exclusión: pacientes del servicio de Reproducción Humana a quienes no se les realizó histeroscopia o ésta fue fallida. Se utilizó el paquete estadístico para las ciencias sociales (SPSS Statistics) versión 20.0. El análisis estadístico fue descriptivo, con media, desviación estándar o porcentaje. RESULTADOS: Se analizaron los expedientes físicos de 440 pacientes infértiles a quienes se efectuó histeroscopia. Las características demográficas incluyeron edad, IMC, tipo y años de infertilidad. Los hallazgos histeroscópicos fueron: cavidad uterina normal 38.4% y anormal 61.6%, pólipo o endometrio polipoide en 34.3%, malformación mülleriana 13.4%, sinequias 10.7%, leiomioma 7.3%, hiperplasia endometrial 1.4%, adenomiosis 0.9%, cuerpo extraño 0.9%. El 7.5% consiguió el embarazo espontáneo y a 21.8% se les practicaron distintas técnicas de reproducción asistida y se logró el embarazo en 34.3%. CONCLUSIONES: La evaluación de la cavidad uterina es un requisito indispensable del estudio de las pacientes infértiles; en esta búsqueda más de la mitad tuvieron hallazgos histeroscópicos anormales.

Abstract OBJECTIVE: To describe the prevalence of endometrial pathology by hysteroscopy among infertile patients in a tertiary referral hospital, from January 2015 to December 2016. MATERIALS AND METHODS: This is a descriptive, retrospective and observational study. The inclusion criteria were patients between 18 and 43 years of age, who had a hysteroscopy due to infertility. The exclusion criteria were patients from Reproductive Science Department who did not undergo hysteroscopy or for whom it failed. We used the software Statistical Package for the Social Sciences (SPSS) version 20.0 Data in this study were analyzed using mean ± standard deviation or expressed as percentages. RESULTS: Four hundred forty infertile women underwent hysteroscopy. Data from physical patient records were retrieved. Demographic characteristics included age, BMI, type of infertility, years of infertility. Hysteroscopic findings were: normal uterine cavity 38.4%, abnormal 61.6%. Some patients had 2 or more findings: polyp or endometrial polypoid 34.3%, müllerian malformation 13.4%, synechia 10.7%, leiomyoma 7.3%, endometrial hyperplasia 1.4%, adenomyosis 0.9%, foreign body 0.9%. In 7.5%, spontaneous pregnancy occurred, 21.8% underwent assisted reproduction technique, achieving pregnancy in 34.3%. CONCLUSIONS: Assessing of uterine cavity should be an indispensable requirement of infertile patients, since in this study more than half of them had abnormal hysteroscopic findings.

Limitación del esfuerzo terapéutico en pacientes con bacteriemia / Limitation of therapeutic effort in patients with bacteremia

Introducción: La limitación del esfuerzo terapéutico (LET) depende de factores médicos, éticos e individuales. Describimos las características de los pacientes con bacteriemia en los que se decidió limitar el esfuerzo terapéutico. Métodos: Estudio prospectivo de las bacteriemias en un hospital comunitario durante el año 2011. Se recogieron variables de los pacientes (edad, sexo, índice de Barthel, comorbilidades, índice de Charlson y factores exógenos) y del episodio infeccioso (etiología, foco, lugar de adquisición, expresividad clínica, LET y mortalidad hospitalaria). Se comparó el grupo en el que se realizó LET con el que no. Resultados: Se recogieron 233 episodios de bacteriemia en 227 pacientes. Se realizó LET en 19 pacientes (8,2%). Los pacientes en los que se realizó LET eran de mayor edad (80,7 vs. 72,6 años, p= 0,014), tenían más comorbilidad (índice de Charlson 4,6 vs. 2,1, p<0,001) y con más frecuencia sufrían discapacidad grave (57,9% vs. 18,8%, p<0,001). No se encontró asociación con el sexo, el lugar de adquisición ni con la expresividad clínica de la infección. El foco clínico más frecuente en los casos de LET fue el urinario (42,1%) y predominaron los grampositivos (63,2%). El tratamiento empírico fue precoz en un 73,7%. Todos los pacientes excepto uno fallecieron. Conclusión: La LET se planteó en un número importante de los pacientes con bacteriemia, especialmente en aquellos con más edad, más comorbilidad y mayor dependencia funcional. El conocimiento de sus características diferenciales nos ayuda a comprender la toma de dicha decisión

Introduction: The limitation of therapeutic effort (LTE) depends on medical, ethical and individual factors. We describe the characteristics of patients with bacteremia in which it was decided to limit the therapeutic effort Method: Prospective study of bacteremia in a community hospital in 2011. We collected information regarding patient variable (age, sex, Barthel index, comorbidities, Charlson Index and exogenous factors) as well as regarding the infectious episode (etiology, focus, place of adquisition, clinical expressivity, LTE and hospital mortality). The group in which LTE was performed was compared to the one that was not. Results: We collected 233 episodes of bacteremia in 227 patients. We performed LTE in 19 patients (8.2%). Patients with LTE were older (80.7 vs. 72.6 years, p=.014), had more comorbidity (Charlson index 4.6 vs. 2.1, p<.001 and most frequently were severe dependents (57.9% vs. 18.8%, p<.001). We found no association with sex, place of adquisition or clinical expressivity. The commonest clinical focus in patients with LTE was the urinary (42.1%) and there was a predominance of gram positive bacteria (63.2%). The empirical treatment was started early in 73.7% of cases. All patients except one died. Conclusion: LTE is considered in an important number of patients with bacteremia. They usually are older, with more comorbidity and functional dependence, bad functional basal status and important comorbidity. Knowing their differential characteristics allow us to understand this decision

[Limitation of therapeutic effort in patients with bacteremia]. / Limitación del esfuerzo terapéutico en pacientes con bacteriemia.

INTRODUCTION: The limitation of therapeutic effort (LTE) depends on medical, ethical and individual factors. We describe the characteristics of patients with bacteremia in which it was decided to limit the therapeutic effort. METHOD: Prospective study of bacteremia in a community hospital in 2011. We collected information regarding patient variable (age, sex, Barthel index, comorbidities, Charlson Index and exogenous factors) as well as regarding the infectious episode (etiology, focus, place of adquisition, clinical expressivity, LTE and hospital mortality). The group in which LTE was performed was compared to the one that was not. RESULTS: We collected 233 episodes of bacteremia in 227 patients. We performed LTE in 19 patients (8.2%). Patients with LTE were older (80.7 vs. 72.6 years, p=.014), had more comorbidity (Charlson index 4.6 vs. 2.1, p<.001 and most frequently were severe dependents (57.9% vs. 18.8%, p<.001). We found no association with sex, place of adquisition or clinical expressivity. The commonest clinical focus in patients with LTE was the urinary (42.1%) and there was a predominance of gram positive bacteria (63.2%). The empirical treatment was started early in 73.7% of cases. All patients except one died. CONCLUSION: LTE is considered in an important number of patients with bacteremia. They usually are older, with more comorbidity and functional dependence, bad functional basal status and important comorbidity. Knowing their differential characteristics allow us to understand this decision.

Tasa acumulada de embarazo clínico y en curso en ciclos de inseminación intrauterina y análisis de los ciclos según la edad, conteo de folículos maduros y estimulación con antagonista de GnRH / Clinical and ongoing cumulative pregnancy rates in cycles of intrauterine insemination and analysis of the cycles according to age, follicular count and GnRH antagonist use

Resumen Objetivo: Determinar la tasa acumulada de embarazo clínico en ciclos de inseminación intrauterina en pacientes estimuladas con gonadotropinas según el número de folículos maduros desarrollados y edad, así como la influencia de los antagonistas de GnRH en su desarrollo y en la tasa de embarazo. Materiales y métodos: Estudio analítico, retrospectivo, en el que se evaluaron ciclos de inseminación intrauterina de pacientes con diferentes protocolos de gonadotropinas en un periodo de dos años. La muestra se dividió en grupos: menores de 35 y más o menos mayores de 35 años y uso o no de antagonista de GnRH. Resultados: Se evaluaron 229 ciclos de inseminación intrauterina en 172 pacientes; de éstas 64% eran menores de 34 años (grupo 1) y 36% mayores de 35 años. El 50% de las pacientes desarrolló de 2 a 3 folículos maduros y 10% de 4 a 6, con una tendencia en aumento de la tasa de embarazo con el desarrollo de hasta 4 folí culos maduros. El antagonista de GnRH no parece relacionarse con mejores tasas de embarazo clínico o en curso en ciclos con más de un folículo maduro. La tasa acumulada de embarazo clínico en tres ciclos fue de 40.6%, mientras que la tasa acumulada de embarazo en curso fue 26.1%. Conclusiones: Hubo relación proporcional entre el número de folículos maduros desarrollados y la tasa de embarazo clínico y en curso. La edad no parece haber tenido influencia en las tasas de em barazo y no pudo demostrarse la eficacia del antagonista en ciclos con desarrollo multifolicular.

Abstract Objective: To determine the cumulative clinical pregnancy rate in cycles of intrauterine insemination with gonadotropin stimulation in relation to number of mature follicles and age and the use of GnRH antagonist on its development. Materials and methods: Analytical, retrospective study in which intrauterine insemination cycles of patients with different gonadotropin protocols were evaluated over a period of two years. The patients were divided in two groups: <35 and ≥35 years old and the use of GnRH antagonist. Results: We evaluated 229 cycles of intrauterine insemination in 172 patients; Of these 64% were under 34 years old (group 1) and 36% over 35 years. The use of antGnRH did not appear to have relation with better clinical and ongoing pregnancy rates in cycles with more than one mature follicle. The cumulative pregnancy rate in three cycles was 40.6%, and cumulative ongoing pregnancy rates was 26.1%. Conclusions: The more mature follicle developed the higher clinical and ongoing pregnancy rates. The age did not appear to have influence in the pregnancy rates, there is no better pregnancy rates with use of antGnRH in cycles with multifolicular developed.

Identification of novel PI3K inhibitors through a scaffold hopping strategy.

A scaffold hopping strategy, including intellectual property availability assessment, was successfully applied for the discovery of novel PI3K inhibitors. Compounds were designed based on the chemical structure of the lead compound ETP-46321, a potent PI3K inhibitor, previously reported by our group. The new generated compounds showed good in vitro potency and selectivity, proved to inhibit potently the phosphorylation of AKTSer473 in cells and demonstrated to be orally bioavailable, thus becoming potential back-up candidates for ETP-46321.