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We describe the case of a 32-year-old man from Cape Verde having headache and increasing visual loss. Clinical and radiological investigations disclosed a massive destructive lesion involving the anterior and central skull base, orbit and nasoethmoid region initially interpreted as a malignant small round cell tumour. Surgical biopsies were negative for neoplasm, showing an intense inflammatory infiltrate together with fungus, later characterised as Aspergillus flavus spp. The patient was immunocompetent with no evidence of congenital or acquired immunodeficiencies. Invasive fungal infections in immunocompetent patients are rare and can be a diagnostic challenge. The best diagnostic clues include the patient’s origin from tropical climates, imaging features and the identification of fungal hyphae on pathology specimens. Although a devastating disease in immunocompromised patients, craniocerebral aspergillosis in immunocompetent patients carries a better prognosis. Available literature supports the combined used of ‘conservative’ surgical resection and antifungal therapy as the best treatment option.

Resumen El dolor neuropatico es un problema clinico importante e incapacitante, su manejo constituye un reto para los profesionales sanitarios. Vortioxetina es un nuevo farmaco antidepresivo con accion multimodal, lo que le confiere un perfil unico. Los antidepresivos triciclicos, en particular amitriptilina, y los inhibidores de la recaptacion de serotonina y noradrenalina venlafaxina y duloxetina constituyen farmacos de primera linea en el tratamiento del dolor neuropatico. La interaccion entre el binomio dolor y depresion es muy frecuente, siendo la complicacion psicologica mas frecuente en los pacientes con dolor cronico. Esta revision exhaustiva y descriptiva resume los datos farmacologicos mas relevantes de vortioxetina, asi como la bibliografia especifica de vortioxetina en dolor neuropatico y dolor cronico.

Introduction The type of body composition modulates the severity of some musculoskeletal conditions, in fibromyalgia syndrome (FMS), this type of association remains relatively unexplored. Objective To analyze the association between the type of body composition and FMS using Principal Component Analysis (PCA). The FMS clinical outcome measures were: Symptom Severity Scale (SSS), Widespread Pain Index (WPI; and Fibromyalgia Impact Questionnaire (FIQ). Methods Forty-three women with FMS (ACR 2010 criteria) were clinically and anthropometrically evaluated. The anthropometric data were integrated into two indicators using a PCA methodology (PCA-Fat and PCA-muscle). Additionally, the patients were classified into high and low categories for each clinical indicator, which were used as dependent variables in binomial logistic regression (BLR) models. Results We found a positive correlation between PCA-Fat with WPI (r = 0.326, P = .043) and FIQ (r = 0.325, P = .044), and negative correlation (r = −0.384, P = .013) between PCA-muscle and SSS. In the BLR analysis, PCA-Fat was a significant predictor for high WPI (OR = 2.477, P = .038); while for high SSS, PCA-muscle (OR = 0.303, P = .009) was an inversely significant predictor. Conclusions The results suggest that the volume of fat mass can negatively modulate the severity of FMS. We propose that the evaluation of body composition should be a basic element for the clinical approach of patients with FMS.

Objectives Maxillary impactions are seen as an orthognathic surgical movement that increases the number of complications. The aim of this paper is to research literature on this topic, with special attention to avoiding of complications. Methods A systematic review was carried out according to the PRISMA guidelines. The PROSPERO registration has been performed. A risk of bias assessment was carried out with RevMan and graphics were created. A total of 20 articles were included in this systematic review. Results Some interesting and conclusive facts about maxillary impactions. Relapses are not common due to the higher bone contact. Bleeding is a common complication due to the location of palatal artery. Aesthetic and functional complications can arise, especially in the nasal region. Bimaxillary orthognathic surgeries has a higher incidence of complications. Conclusions Today it is not possible to confirm that maxillary impactions alone are responsible for a higher incidence of complications due to the complexity of the three-dimensional movements. Some surgical steps could be safer and cause fewer complications.

International audience; Maintaining up-to-date KVM hypervisors requires regular upgrades to the host kernel, hence rebooting the physical host with the consequent termination of running Virtual Machines (VMs). Cloud platforms capable of massive large-scale live migrations evacuate VMs from the hosts before rebooting, minimizing the impact over VM up-time. However, scenarios exist where resource constraints make live migration undesirable, or the presence of fault-tolerant instances (e.g., replicated services) favors the adoption of VM termination, a simpler but more disruptive strategy. In this article, we present Hy-FiX, a fast in-place upgrade solution for KVM hypervisors. Hy-FiX preserves VM memory across host reboots, protecting the execution state of running guests while hypervisor upgrades are applied. Hy-FiX memory preservation across reboot, combined with a mixed suspend-to-disk/suspend-to-RAM technique, achieves a 2.31-second checkpoint/restore time for a 256 GB VM, and Hy-FiX lazy memory initialization reboots an enterprise-class host in constant time (7.6 seconds) regardless of its equipped memory. Hy-FiX is, therefore, a better alternative to classical VM termination and restart.

Resumen Introduccion La relacion entre eventos adversos y aplicacion de medicamentos biologicos en pacientes con diagnostico de artritis reumatoide ha sido documentada a escala mundial, pero con escasa evidencia en Colombia. Si se asume que los eventos adversos o reacciones medicamentosas con hallazgos clinicos relevantes en la salud, como consecuencia de este tratamiento terapeutico, recaen sobre la calidad de vida del paciente e influyen en los indicadores de salud a escala nacional y en los recursos del sistema, se hace importante evaluar su impacto. Objetivos Determinar la frecuencia de eventos adversos o reacciones adversas relacionados con el uso de medicamentos biologicos en una cohorte de pacientes con diagnostico de artritis reumatoide de una aseguradora nacional, en el periodo comprendido entre los anos 2000 y 2019. Metodologia Se realizo un estudio descriptivo, transversal y retrospectivo, con alcance analitico, en pacientes diagnosticados de artritis reumatoide, con terapia biologica, en una aseguradora a escala nacional, con registros en historias clinicas del ano 2000 al 2019. Resultados Se analizaron 252 registros clinicos de usuarios con diagnostico de artritis reumatoide y terapia biologica. El 62,7% presento al menos una reaccion adversa y se evaluaron 9 farmacos: tocilizumab, etanercept, adalimumab, abatacept, certolizumab, golimumab, infliximab, rituximab y tofacitinib. Este ultimo es un farmaco incluido en este estudio por solicitud de la aseguradora fuente de la informacion. Conclusiones En la terapia biologica de pacientes con artritis reumatoide las reacciones adversas son frecuentes, y en un 27,3% resultan severas, lo cual describe una situacion previamente desconocida en Colombia.

Background: Addressing the high prevalence of disease-related malnutrition (DRM) requires political will. The aim of this study is to define DRM as a health public policy issue from the point of view of the stakeholders. Methods: We conducted a qualitative phenomenological study consisting of grey data search and individual semi-structured in-depth interviews with stakeholders (policy-makers, academics, and civil society organization representatives) from 17 Latin American countries. The analyzed themes reflected ideas repeatedly found across the interviews. Results: 26 respondents were interviewed (5 policy-makers, 18 academics, 3 civil society organizations representatives). The grey data research and interviews showed that Brazil and Costa Rica were the only countries in the Region that had developed a specific public health policy addressing DRM and nutrition care issues. The rest of the Latin American countries had a nutrition policy which neither addressed DRM specifically nor included nutrition care, with important heterogeneity existing in terms of national regulation of selected nutritional care categories. Stakeholder opinions allowed to identify heterogeneity in the understanding of the nature and causes of DRM, confusing DRM with malnutrition caused by food insecurity and lack of food availability. Policy in the field of clinical nutrition can be addresses from two approaches: interdisciplinarity and a human rights-based approach. Conclusion: DRM is an unaddressed problem by health policy. Due to internal and external factor related to the health systems DRM has not been able to become a public policy issue. The study highlights the need for the development of public policy in clinical nutrition aimed at improving access to nutrition care. © 2021 European Society for Clinical Nutrition and Metabolism Background: Addressing the high prevalence of disease-related malnutrition (DRM) requires political will. The aim of this study is to define DRM as a health public policy issue from the point of view of the stakeholders. Methods: We conducted a qualitative phenomenological study consisting of grey data search and individual semi-structured in-depth interviews with stakeholders (policy-makers, academics, and civil society organization representatives) from 17 Latin American countries. The analyzed themes reflected ideas repeatedly found across the interviews. Results: 26 respondents were interviewed (5 policy-makers, 18 academics, 3 civil society organizations representatives). The grey data research and interviews showed that Brazil and Costa Rica were the only countries in the Region that had developed a specific public health policy addressing DRM and nutrition care issues. The rest of the Latin American countries had a nutrition policy which neither addressed DRM specifically nor included nutrition care, with important heterogeneity existing in terms of national regulation of selected nutritional care categories. Stakeholder opinions allowed to identify heterogeneity in the understanding of the nature and causes of DRM, confusing DRM with malnutrition caused by food insecurity and lack of food availability. Policy in the field of clinical nutrition can be addresses from two approaches: interdisciplinarity and a human rights-based approach. Conclusion: DRM is an unaddressed problem by health policy. Due to internal and external factor related to the health systems DRM has not been able to become a public policy issue. The study highlights the need for the development of public policy in clinical nutrition aimed at improving access to nutrition care. © 2021 European Society for Clinical Nutrition and Metabolism

INTRODUCTION AND AIM Helicobacter pylori (H. pylori) is known to be capable of causing chronic inflammation of the gastric mucosa that slowly progresses through the premalignant stages, reaching localized gastric adenocarcinoma (GAC). Its outcome is closely related to the stage at which diagnosis is made. The aim of the present study was to determine cost-benefit by comparing esophagogastroduodenoscopy, serum pepsinogen detection, and no screening at all. MATERIAL AND METHODS Utilizing Markov chains and Monte Carlo simulation, the costs and effects of various detection modalities were simulated to analyze the cost-benefit of each strategy. For our population, we used the published data of patients with gastric cancer, applicable to the Mexican population. RESULTS The results were reported as incremental cost-effectiveness ratios. The best strategy was serum pepsinogen determination, followed by the strategy of endoscopic examination with continued monitoring every 3 years. CONCLUSIONS The performance of serum pepsinogen serology and directed endoscopic examination (and continued monitoring, if necessary) for GAC screening could be a cost-effective intervention in Mexico, despite the low-to-moderate general prevalence of the disease.

Objectives (a) to evaluate and compare the psychological treatment needs of patients with cancer and non-cancer, who are going to undergo scheduled thoracic surgery, and (b) evaluate and compare the diagnostic accuracy of the screening tests of psychological treatment needs for cancer and non-cancer patients. Method The need for psychological treatment was evaluated in a total of 169 patients prior to thoracic surgery, through a clinical interview. The screening tests used were: the physician's judgment (yes/no), the Hospital Anxiety and Depression Scale (HADS) and, the single-item interview to assess depression “Do you feel depressed?” (DEPQ). Results The number of patients who needed psychological treatment in the total sample was 47 (27.81%), in non-cancer-patients: 22 (30.99%) and in cancer patients: 25 (25.51%). The participants with treatment needs were more often young women with primary education levels, with more fears and concerns regarding their disease. With respect to the screening tests, the HADS-T (cut-off point ≥13) obtained a sensitivity (SE) of 0.75 and Specificity (SP) of 0.81 in the total sample. In patients with cancer, the HADS total score (cut-off point ≥10) obtained an SE = 0.84 and SP = 0.80, and, in non-cancer patients, the HADS total score (cut-off point ≥13) showed an SE = 0.59 and SP = 0.84. The DEPQ and the physician's judgment did not achieve adequate levels of precision. Conclusions A high percentage of patients have psychological treatment needs before performing thoracic surgery, which are similar for cancer and non-cancer patients. Preoperative detection of patients who need psychological intervention is feasible with a simple screening test: HADS, which achieves greater precision in cancer patients.

Introduction Influenza epidemics are of higher risk at the extremes of life and in people with comorbidities. Effective vaccination prevents the occurrence of serious cases and decreases mortality. Objective To describe deaths from influenza with a history of timely vaccination, from the 2010 to the 2018 season in Mexico. Method Cross-sectional, descriptive study where the Influenza Epidemiological Surveillance System database was used. Results From 2010 to 2018, 65 vaccinated individuals died from influenza, from which 55% of cases (n = 36) were due to type A (H1N1), 51% (n = 33) were females, median age was 57 years, 21 % (n = 14) did not meet the operational definition of influenza-like illness or severe acute respiratory infection, 83% (n = 54) had at least one comorbidity, with the most common being diabetes mellitus and hypertension (32% each); 55% (n = 36) of deaths received antiviral treatment and only 8% (n = 5) had no comorbidities and received treatment with oseltamivir. Conclusions Deaths from influenza with timely vaccination represent a very low percentage of the totality. Vaccination against influenza has been a specific prevention strategy that decreases disease burden.

BACKGROUND The long-term outcomes of diabetic patients presenting with ST-segment elevation myocardial infarction (STEMI) in contemporary practice have received limited study. METHODS We evaluated the clinical characteristics and outcomes of STEMI patients with and without diabetes in a large regional STEMI program designed to facilitate timely primary percutaneous coronary intervention (PCI) (Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis, MN). The primary and secondary outcome measures were in-hospital mortality, 1-year major adverse cardiovascular events (MACE) (stroke, myocardial infarction, unplanned PCI or coronary artery bypass graft [CABG] surgery, and all-cause mortality), and 5-year mortality. RESULTS Of the 6292 patients included, 1158 (18.4%) had Diabetes Mellitus (DM) (95.3% Type II, 4.7% Type I). Patients with DM were older (mean age 66 vs. 62.8 years, p < 0.01), had more co-morbidities and were more likely to receive medical therapy without reperfusion (13% vs. 10%, p = 0.003). Patients with DM had higher in-hospital (8% vs. 5%, p = 0.001), 1-year (8% vs. 4%, p < 0.001) and 5-year mortality (16% vs. 9%, p < 0.001) compared to non-diabetics. On Cox proportional hazards analysis, DM was independently associated with worse mortality (hazard ratio: 1.70, 95% confidence interval (CI): 1.32-2.19, p < 0.001) and MACE [HR: 1.63 (95% (CI)): 1.28-2.08, p < 0.001]. CONCLUSIONS Despite advancements in medical therapy and revascularization strategies for STEMI, DM remains independently associated with higher short- and long-term morbidity and mortality in contemporary practice.

RESEARCH QUESTION: Does magnetic-activated cell sorting (MACS) for sperm selection increase cumulative live birth rates (CLBR) or improve clinical parameters of reproductive success in couples undergoing intracytoplasmic sperm injection (ICSI) with donor oocytes? DESIGN: Retrospective multicentre observational study including data compiled from unselected couples who underwent ICSI cycles with donated oocytes in 15 Spanish IVIRMA fertility clinics (January 2008 to February 2020). Patients were divided into reference (standard semen processing, n = 40,157) and MACS (additional sperm selection step by MACS, n = 1,240) groups. CLBR were plotted on Kaplan-Meier curves and compared using the Mantel-Cox test. Proportions were compared with a generalized estimating equation model, and results were adjusted to clinically relevant variables. RESULTS: The MACS group showed a 27.1% CLBR after one embryo was transferred and 81.6% after four; the reference group had CLBR of 19.6% and 78.5%, respectively. CLBR in the MACS group was 4.2% after five oocytes were used and 75.5% after 15; for the reference group, CLBR were 7.8% and 78.3%, respectively. Kaplan-Meier curves showed statistically significant differences in CLBR per number of embryos transferred and per number of donated metaphase II oocytes between the two groups (both P

Postmortem normothermic regional perfusion (NRP) is a rising preservation strategy in controlled donation after circulatory determination of death (cDCD). Herein, we present results for cDCD liver transplants performed in Spain 2012-2019, with outcomes evaluated through December 31, 2020. Results were analyzed retrospectively and according to recovery technique (abdominal NRP [A-NRP] or standard rapid recovery [SRR]). During the study period, 545 cDCD liver transplants were performed with A-NRP and 258 with SRR. Median donor age was 59 years (interquartile range 49-67 years). Adjusted risk estimates were improved with A-NRP for overall biliary complications (OR 0.300, 95% CI 0.197-0.459, p

This Atlas chapter summarizes sex- and some gender-associated, and unique aspects and manifestations of cardiovascular disease (CVD) in women. CVD is the primary cause of premature death in women in Canada and numerous sex-specific differences related to symptoms and pathophysiology exist. A review of the literature was done to identify sex-specific differences in symptoms, pathophysiology, and unique manifestations of CVD in women. Although women with ischemic heart disease might present with chest pain, the description of symptoms, delay between symptom onset and seeking medical attention, and prodromal symptoms are often different in women, compared with men. Nonatherosclerotic causes of angina and myocardial infarction, such as spontaneous coronary artery dissection are predominantly identified in women. Obstructive and nonobstructive coronary artery disease, aortic aneurysmal disease, and peripheral artery disease have worse outcomes in women compared with men. Sex differences exist in valvular heart disease and cardiomyopathies. Heart failure with preserved ejection fraction is more often diagnosed in women, who experience better survival after a heart failure diagnosis. Stroke might occur across the lifespan in women, who are at higher risk of stroke-related disability and age-specific mortality. Sex- and gender-unique differences exist in symptoms and pathophysiology of CVD in women. These differences must be considered when evaluating CVD manifestations, because they affect management and prognosis of cardiovascular conditions in women.Dans le présent chapitre d’Atlas sont récapitulés les aspects et les manifestations uniques, associés au sexe et certains associés au genre, des maladies cardiovasculaires (MCV) chez les femmes. Les MCV sont la cause principale de décès prématurés chez les femmes au Canada. De nombreuses différences quant aux symptômes et à la physiopathologie existent entre les sexes. Nous avons réalisé une revue de la littérature pour déterminer les différences entre les sexes dans les symptômes et la physiopathologie, et les manifestations uniques des MCV chez les femmes. Bien que les femmes atteintes d’une cardiopathie ischémique puissent éprouver des douleurs thoraciques, la description des symptômes, le délai entre l’apparition des symptômes et l’obtention de soins médicaux, et les symptômes prodromiques sont souvent différents de ceux des hommes. Les causes de l’angine et de l’infarctus du myocarde non liées à l’athérosclérose telles que la dissection spontanée de l’artère coronaire sont principalement observées chez les femmes. La coronaropathie obstructive et non obstructive, l’anévrisme aortique et la maladie artérielle périphérique montrent de plus mauvaises issues chez les femmes que chez les hommes. Des différences entre les sexes sont observées dans la cardiopathie valvulaire et les cardiomyopathies. Le diagnostic d’insuffisance cardiaque avec fraction d’éjection préservée est plus souvent posé chez les femmes qui présentent un meilleur taux de survie après un diagnostic d’insuffisance cardiaque. L’accident vasculaire cérébral (AVC) pourrait survenir tout au long de la vie des femmes, qui sont exposées à un risque plus élevé d’incapacités liées à l’AVC et de mortalité par âge. Il existe des différences uniques entre les sexes et les genres pour ce qui est des symptômes et de la physiopathologie des MCV chez les femmes. Lors de l’évaluation des manifestations des MCV, il faut tenir compte de ces différences puisqu’elles influencent la prise en charge et le pronostic des maladies cardiovasculaires chez les femmes.

Resumen Introduccion y objetivo Aunque los comites multidisciplinares (CMD) estan recomendados en el manejo del cancer de prostata avanzado (CPA), su funcionamiento en practica real se ha evaluado escasamente. Desarrollamos un estudio multicentrico con el objetivo de evaluar el funcionamiento de los CMD urooncologicos en seis hospitales. Materiales y metodos Realizamos un estudio transversal descriptivo. El nivel de cumplimiento de los requisitos de calidad fundamentales (CRCF) de los CMD, se evaluo aplicando un cuestionario a los coordinadores de los CMD de cada hospital. La perspectiva de los miembros de los CMD se evaluo aplicando una encuesta anonima telematica. Resultados Evidenciamos un alto nivel de CRCF en los CMD (75%), mostrando deficiencias en la actualizacion de protocolos, agendas, auditorias y produccion cientifica. La encuesta fue respondida por un 62,32% de los 69 medicos encuestados (urologos, oncologos, radioterapeutas, radiologos y anatomopatologos). El 88,4% considera adecuado el tiempo de las reuniones. Existen opiniones dispares sobre la proteccion del tiempo de las reuniones y la actualizacion de protocolos. El 62,8% de los pacientes presentados requieren la intervencion de dos especialidades. La mitad de los encuestados cree que se discuten todos los casos de CPRC y que existe una agenda previa. Las decisiones del CMD quedan reflejadas en la historia clinica en un 65,1% y son vinculantes en un 60,5%. La mitad de los encuestados niegan capacitacion en CMD. La mayoria de los participantes (90,7%) avalan los beneficios de los CMD. Conclusiones Las evaluaciones de los CMD identifican deficiencias subsanables modificando la inercia hospitalaria y la planificacion asistencial.

Night work is one of the most recognized responsibilities of security personnel. Feeling vital is a necessary condition for assuring proper development of this function. Thus, the analysis of its effects on physical and mental conditions is a relevant resource for achieving adequate results at individual and organizational levels. Based on a questionnaire applied to 184 private security guards in Colombia, this study examines the subjective vitality of the personnel working during night shifts and its association with self-perceptions regarding their physical and mental health. Additionally, it analyzes the interference that various demographic variables exert on these relationships. By using partial least squares structural equation modeling, the study found that subjective vitality significantly affects night workers’ mental health more than their physical health. That is, subjective vitality among respondents explains 51% of the variability of mental health and 36% of the variability of physical health. A further significant effect of physical health on mental health was also evidenced, in which the former explains the 25% of the latter variability. When comparing results between genders, the study shows that the variability of mental health explained by subjective vitality among women is larger than among men (75% vs. 28%). These results are discussed in light of the theoretical aspects of organizational behavior and are grounded around their potential to address the phenomenon of human resource management in practice. Practical implications include the need for organizational schemes that balance physical and mental health among night workers. AcknowledgmentsThe authors want to acknowledge the 184 Colombian security guards who provided their time to complete the questionnaire for this study.

Objective To estimate the annual cost associated with obstetric events in women of reproductive age with immune-mediated inflammatory diseases, from the perspective of the National Healthcare System. Methods A cost-analysis was developed to estimate the impact associated with obstetric events in women of reproductive age with psoriasis (PSO), psoriatic arthritis (PsA), rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA). The analysis considered complications during fertility and conception, in pregnancy and in the postpartum. All parameters were validated and agreed by a multidisciplinary expert panel. Unitary costs (€, 2019) were obtained from national, local databases. Results During fertility and conception, an annual cost per patient of €229 was estimated for a preconception consultation in a patient with PSO, of €3,642 for a preconception consultation in patients with PsA, RA and axSpA and €4,339 for assisted reproduction. Women with complications in pregnancy had an annual cost per patient of €1,214 for a miscarriage in the first trimester, €4,419 for a late miscarriage in the second trimester, €11,260 for preeclampsia €3,188 for restricted intrauterine growth and €12,131 for threat of premature delivery. In the postpartum, an annual cost per patient of €120,364, €44,709, and €5,507 were estimated associated with admissions to neonatology of premature infants of Conclusions This analysis provides insight on the economic burden of complications associated with women of reproductive age for immune-mediated diseases (PSO, PsA, RA, axSpA). Individualization of treatment, additional and close monitoring may reduce the risk and burden of these complications.

Taking advantage of the superflat surface of ultrananocrystalline diamond (UNCD), highly precise UNCD nanowire (NW) arrays were fabricated to develop high-performance UV photodetectors. The large surface-to-volume ratio of a nanowire significantly increases the number of surface trap states, and the reduced dimensionality effectively confines the active area of the charge carrier and shortens the transit time, which results in an enhanced photoconductivity and response speed. In this paper, the zero-biased UV photodetectors based on nitrogen-incorporated ultrananocrystalline diamond nanowire arrays have been demonstrated and characterized. The estimated responsivity was 2.0 A/W for 350 nm incident light when the device operated at room temperature. The UVA and UVB photocurrent signals from this visible blind photodetector were well defined with a rise and decay time of less than 1 s.

Background Human epidermal growth factor receptor 2 (HER2)-targeted therapies have not been approved for patients with non-small-cell lung cancer (NSCLC). The efficacy and safety of trastuzumab deruxtecan (formerly DS-8201), a HER2 antibody-drug conjugate, in patients with HER2-mutant NSCLC have not been investigated extensively. Methods We conducted a multicenter, international, phase 2 study in which trastuzumab deruxtecan (6.4 mg per kilogram of body weight) was administered to patients who had metastatic HER2-mutant NSCLC that was refractory to standard treatment. The primary outcome was objective response as assessed by independent central review. Secondary outcomes included the duration of response, progression-free survival, overall survival, and safety. Biomarkers of HER2 alterations were assessed. Results A total of 91 patients were enrolled. The median duration of follow-up was 13.1 months (range, 0.7 to 29.1). Centrally confirmed objective response occurred in 55% of the patients (95% confidence interval [CI], 44 to 65). The median duration of response was 9.3 months (95% CI, 5.7 to 14.7). Median progression-free survival was 8.2 months (95% CI, 6.0 to 11.9), and median overall survival was 17.8 months (95% CI, 13.8 to 22.1). The safety profile was generally consistent with those from previous studies; grade 3 or higher drug-related adverse events occurred in 46% of patients, the most common event being neutropenia (in 19%). Adjudicated drug-related interstitial lung disease occurred in 26% of patients and resulted in death in 2 patients. Responses were observed across different HER2 mutation subtypes, as well as in patients with no detectable HER2 expression or HER2 amplification. Conclusions Trastuzumab deruxtecan showed durable anticancer activity in patients with previously treated HER2-mutant NSCLC. The safety profile included interstitial lung disease that was fatal in two cases. Observed toxic effects were generally consistent with those in previously reported studies. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Lung01 ClinicalTrials.gov number, NCT03505710.).

La educación en Arequipa se enfrenta a contingencias especiales, ocasionadas por la COVID-19, lo que implica procesos condicionados a una educación superior virtual, generando escenarios que hacen necesario replantear las estrategias de compromiso entre sus protagonistas, estudiando la interactividad de los estudiantes y la retroalimentación de los docentes en la asignatura de investigación científica en la Escuela de Ciencias de la Comunicación de la Universidad Nacional de San Agustín. El objetivo de la investigación es el estudio de la implementación del aprendizaje colaborativo en una cultura interactiva del proceso enseñanza–aprendizaje desde un enfoque complejo, identificando los condicionamientos socioeconómicos actuales. La metodología de investigación aplicada es mixta, cualicuantitativa transversal no experimental, que nos permite reconocer a la colaboración como parte fundamental de la evaluación, que, además incentiva una mayor interactividad generando un clima constructivo en el proceso educativo. Se concluye que los métodos colaboracionistas además de coadyuvar a crear nuevo conocimiento, fortalecen el sentido del trabajo en equipo desde diferentes disciplinas, aun dentro de condicionamientos socioeconómicos.

Objective To report our experience with r obot- a ssisted (RA) autologous cryopreserved ovarian tissue transplantation (ACOTT) with the use of a neovascularizing extracellular matrix scaffold. Design Case series with meta-analytic update. Setting Academic. Patient(s) Seven recipients of RA-ACOTT. Intervention(s) Before or shortly after initiating chemotherapy, ovarian tissue was cryopreserved from 7 women, who then underwent RA-ACOTT 9.9 ± 1.8 years (range, 7–12 years) later. Perioperatively, they received transdermal estrogen and low-dose aspirin to enhance graft vascularization. Ovarian cortical pieces were thawed and sutured on an extracellular matrix scaffold, which was then robotically anastomosed to the bivalved remaining ovary in 6 cases and retroperitoneally (heterotopic) to the lower abdomen in 1 case. Main Outcome Measure(s) Ovarian function return, the number of oocytes/embryos, aneuploidy %, live births, and neonatal outcomes were recorded. Graft longevity was compared with the mean from the meta-analytic data. Result(s) Ovarian function returned 13.9 ± 2.7 weeks (11–16.2 weeks) after ACOTT, and oocytes were retrieved in all cases with 12.3 ± 6.9 embryos generated. In contrast to orthotopic, the heterotopic ACOTT demonstrated low embryo quality and an 80% aneuploidy rate. A recipient did not attempt to conceive and 2 needed a surrogate, whereas 4 of 4 delivered 6 healthy children, compared with 115 of 460 (25% pregnancy rate) from the meta-analytic data (n = 79). The mean graft longevity (43.2 ± 23.6/47.4 ± 22.8 months with/without sensitivity analysis) trended longer than the meta-analytic mean (29.4 ± 22.7), even after matching age at cryopreservation. Conclusion(s) In this series, RA-ACOTT resulted in extended graft longevity, with ovarian functions restored in all cases, even when the tissues were cryopreserved after chemotherapy exposure.

Background We aimed to describe the effectiveness and safety of inhaled antibiotics in chronic obstructive pulmonary disease (COPD) patients, as well as the patient profile in which they are usually prescribed and the patient groups that can most benefit from this treatment. Methods Multicentre retrospective observational cohort study in COPD patients who had received ≥1 dose of inhaled antibiotics in the last 5 years. Clinical data from the two years prior to and subsequent to the start of the treatment were compared. Primary outcome: COPD exacerbations. Secondary outcomes: side effects, symptomatology (sputum purulence, dyspnoea), microbiological profile and pathogen eradication. Results Of 693 COPD patients analyzed (aged 74.1; 86.3% men; mean FEV1 = 43.7%), 71.7% had bronchiectasis and 46.6% presented chronic bronchial infection (CBI) by Pseudomonas aeruginosa (PA). After 1 year of treatment with inhaled antibiotics, there was a significant decrease in the number of exacerbations (−33.3%; P Conclusions In COPD patients with multiple exacerbations and/or CBI by any PPM (especially PA), inhaled antibiotics appear to be an effective and safe treatment, regardless of the presence of bronchiectasis.

Key Points Stem cell transplant improves long-term survival in T/NK CAEBV, though mortality remains high.Development of T/NK lymphoma showed a trend with increased mortality., Visual Abstract, Chronic active Epstein-Barr virus (EBV) disease (CAEBV) is characterized by high levels of EBV predominantly in T and/or natural killer cells with lymphoproliferation, organ failure due to infiltration of tissues with virus-infected cells, hemophagocytic lymphohistiocytosis, and/or lymphoma. The disease is more common in Asia than in the United States and Europe. Although allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only curative therapy for CAEBV, its efficacy and the best treatment modality to reduce disease severity prior to HSCT is unknown. Here, we retrospectively assessed an international cohort of 57 patients outside of Asia. Treatment of the disease varied widely, although most patients ultimately proceeded to HSCT. Though patients undergoing HSCT had better survival than those who did not (55% vs 25%, P < .01), there was still a high rate of death in both groups. Mortality was largely not affected by age, ethnicity, cell-type involvement, or disease complications, but development of lymphoma showed a trend with increased mortality (56% vs 35%, P = .1). The overwhelming majority (75%) of patients who died after HSCT succumbed to relapsed disease. CAEBV remains challenging to treat when advanced disease is present. Outcomes would likely improve with better disease control strategies, earlier referral for HSCT, and close follow-up after HSCT including aggressive management of rising EBV DNA levels in the blood.

Context Patients with chronic pelvic pain syndrome (CPPS) may have pain refractory to conventional management strategies. Botulinum toxin A (BTX-A) is a potential therapeutic option. Objective To evaluate the benefits and harms of BTX-A injections in the treatment of CPPS. Evidence acquisition A systematic review of the use of BTX-A in the treatment of CPPS was conducted (PROSPERO-ID: 162416). Comprehensive searches of EMBASE, PUBMED, Medline, and SCOPUS were performed for publications between January 1996 and May 2020. Identified studies were screened and selected studies assessed for quality prior to data extraction. The primary outcomes were improvement in pain and adverse events following treatment. Secondary outcomes included quality of life, global response assessment, sexual function, bowel function, and bladder function. Evidence synthesis After screening 1001 abstracts, 16 studies including 11 randomised controlled trials were identified, enrolling 858 patients and covering a range of CPPS subtypes. Most studies showed high risks of bias and confounding across all domains. A narrative synthesis was performed as heterogeneity of included studies precluded a meta-analysis and calculation of pooled effect estimates of measured outcomes. BTX-A reduced pain significantly in patients with bladder pain syndrome in two studies and in patients with prostate pain syndrome in one study, but no included studies showed benefit for patients with gynaecological pelvic pain. Adverse event reporting was variable and generally poor, but no serious adverse events were described. Conclusions Beneficial effects of BTX-A on pain, quality of life, and functional symptoms were seen in patients with certain CPPS subtypes, but the current evidence level is too weak to allow recommendations about BTX-A use for treating CPPS. Patient summary Botulinum toxin A is used to treat different pain disorders, but current studies are of insufficient quality to determine whether it reduces pain and improves quality of life in patients with chronic pelvic pain. Further research is needed.

Transcranial direct current stimulation (tDCS) has been widely used to modulate cognition and behavior. However, only a few studies have been probing the brain mechanism underlying the effects of tDCS on cognitive processing, especially throughout electrophysiological markers, such as the P3. This meta-analysis assessed the effects of tDCS in P3 amplitude and latency during an oddball, n-back, and Go/No-Go tasks, as well as during emotional processing. A total of 36 studies were identified, but only 23 were included in the quantitative analysis. The results show that the parietal P3 amplitude increased during oddball and n-back tasks, mostly after anodal stimulation over the left dorsolateral prefrontal cortex (p = 0.018, SMD = 0.4) and right inferior frontal gyrus (p

High operation and maintenance costs, and ‘last-mile’ issues for populations not connected to municipal water infrastructure, have limited the utility of centralized reverse osmosis (RO) systems to alleviate water availability issues for rural communities. To address these challenges, a decentralized RO module which employs tubular RO membranes was designed and investigated. The system represents an appropriate technology because it requires minimal pretreatment and it fits in self-contained, low-profile suitcase. This compact desgin also incorporated innovative 3D printed static mixers to minimize salt concentration polarization and to improve performance. Since grid electricity may also be discontinuous in the target use cases, the system was tested with two direct current (DC) power solutions: a photovoltaics-battery configuration and an alternator-battery. The final prototype weighs less than 15 kg and was found to have a production capacity of ∼8 L/h, consuming ∼100 W of pumping power. Experiments of the prototype module revealed a 96% rejection rate of salt from a 1000–2000 ppm synthetic groundwater solution and a >99% rejection coefficient for bovine serum albumin protein and humic acid. From these performance metrics, it was estimated that 36 sets of this decentralized system (with a total CapEx of US$23,400) could provide drinking water for ∼600 rural households at a unit cost of water of 1 LKR/L (0.005 USD/L) in Sri Lanka. Overall, this study demonstrates how computational modeling and 3D printing can be leveraged to develop a compact and cost-effective decentralized RO package that could be rapidly deployed to water-stressed rural areas and in disaster relief applications.

Background W1282X-CFTR variant (c.3846G>A) is the second most common nonsense cystic fibrosis (CF)-causing mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene. Even though remarkable breakthroughs have been done towards CF treatment with the approval of four CFTR protein modulators, none of these are approved for patients with nonsense mutations. CRISPR gene editing tools can be of great value to permanently correct the genetic defects caused by these mutations. Methods We compared the capacity of homology-directed repair (HDR) mediated by Cas9 or Cas12a to correct W1282X CFTR mutation in the CFF-16HBEge W1282X CFTR cell line (obtained from CFF), using Cas9/gRNA and Cas12a/gRNA ribonucleoproteins (RNPs) and single strand DNA (ssODN) oligonucleotide donors. Results Cas9 shows higher levels of correction than Cas12a as, by electroporating cells with Cas9 RNPs and ssODN donor, nearly 18% of precise editing was achieved compared to just 8% for Cas12a. Such levels of correction increase the abundance of CFTR mRNA and protein, and partially restore CFTR function in the pool of edited cells to 18% of WT CFTR function. Moreover, homozygous corrected clones produced levels of mRNA, protein, and function comparable to those of cells expressing WT CFTR. Conclusion Altogether, this work demonstrates the potential of gene editing as a therapeutic strategy for CF directly correcting the root cause of the disease.

The case is presented of a girl diagnosed with obstructive hydrocephalus due to pilomyxoid astrocytoma, which required a ventriculoperitoneal shunt (VPS) at the age of 5 years and 10 months. Two months later, magnetic resonance imaging of the brain did not show ventriculomegaly or other signs of increased intracranial pressure. At the age of 6 years and 2 months, a rapid onset of bilateral visual acuity loss developed and she was diagnosed with slit ventricle syndrome. Despite valve revisions of the VPS, she developed an abrupt decline of visual acuity to hand motion at 10cm. Fundus examination revealed bilateral optic atrophy. She did not report any other systemic symptoms suggesting increased intracranial pressure, such as headache, nausea, vomiting, lethargy, irritability, or altered levels of consciousness.

Summary Background Patients with COVID-19 pneumonia can have increased inflammation and elevated cytokines, including interleukin (IL)-6, which might be deleterious. Thus, sarilumab, a high-affinity anti-IL-6 receptor antibody, might improve the outcome of patients with moderate-to-severe COVID-19 pneumonia. Methods We did a multicentric, open-label, Bayesian randomised, adaptive, phase 2/3 clinical trial, nested within the CORIMUNO-19 cohort, to test a superiority hypothesis. Patients 18 years or older hospitalised with COVID-19 in six French centres, requiring at least 3L/min of oxygen but without ventilation assistance and a WHO Clinical Progression Scale [CPS] score of 5 were enrolled. Patients were randomly assigned (1:1) via a web-based system, according to a randomisation list stratified on centre and with blocks randomly selected among 2 and 4, to receive usual care plus 400 mg of sarilumab intravenously on day 1 and on day 3 if clinically indicated (sarilumab group) or usual care alone (usual care group). Primary outcomes were the proportion of patients with WHO-CPS scores greater than 5 on the 10-point scale on day 4 and survival without invasive or non-invasive ventilation at day 14. This completed trial is closed to new participants and is registered with ClinicalTrials.gov , NCT04324073 . Findings 165 patients were recruited from March 27 to April 6, 2020, and 148 patients were randomised (68 patients to the sarilumab group and 80 to the usual care group) and followed up for 90 days. Median age was 61·7 years [IQR 53·0–71·1] in the sarilumab group and 62·8 years [56·0–71·7] in the usual care group. In the sarilumab group 49 (72%) of 68 were men and in the usual care group 59 (78%) of 76 were men. Four patients in the usual care group withdrew consent and were not analysed. 18 (26%) of 68 patients in the sarilumab group had a WHO-CPS score greater than 5 at day 4 versus 20 (26%) of 76 in the usual care group (median posterior absolute risk difference 0·2%; 90% credible interval [CrI] −11·7 to 12·2), with a posterior probability of absolute risk difference greater than 0 of 48·9%. At day 14, 25 (37%) patients in the sarilumab and 26 (34%) patients in the usual care group needed ventilation or died, (median posterior hazard ratio [HR] 1·10; 90% CrI 0·69–1·74) with a posterior probability HR greater than 1 of 37·4%. Serious adverse events occurred in 27 (40%) patients in the sarilumab group and 28 (37%) patients in the usual care group (p=0·73). Interpretation Sarilumab treatment did not improve early outcomes in patients with moderate-to-severe COVID-19 pneumonia. Further studies are warranted to evaluate the effect of sarilumab on long-term survival. Funding Assistance publique—Hopitaux de Paris

Introduction and aims: Oropharyngeal dysphagia (OD) occurs in children with cerebral palsy. It is important to investigate its relationship with some variables, and the objective of this study was to identify factors associated with OD. Materials and methods: Case-control study in patients with cerebral palsy from 8 months to 15 years of age, from November 2018 to November 2019, approved by the Ethics Committee. The diagnosis of OD was made by videofluoroscopy when there was nasopharyngeal reflux, stagnation in the vallecular sinuses, in the piriformis sinuses, penetration, and aspiration. The independent variables were type of cerebral palsy, gross motor impairment classified into five levels, nutritional status and comorbidities. One case with OD was included and the next one without alterations in videofluoroscopy was control. The variables were compared with Chi square and Student's t. The association was measured with odds ratio. The confidence interval was 95%. Results: Thirty patients with OD and 30 without OD were studied. Sex, age, birth weight, and gestational age had a similar distribution in the two groups. From the data perceived by the mothers at the time of feeding, the greater frequency of the difficulty in the transfer of the food bolus in the group with OD showed a statistically significant difference (P

Islands have the potential to be precursors in the transition to clean energy, by adopting new technologies and applying innovative solutions that can serve as showcases at an international level. This paper is a contribution towards understating the importance of community engagement on energy transition processes. It covers multiple aspects of a green transition process, including technical, environmental, social, and economic issues. Starting by a participatory diagnosis process, the community of a small island located in Portugal (Culatra Island, Algarve), was challenged to lead the transition process and define different pillars of energy transition. The process brought together local authorities, academia, citizens and companies. Using practical examples, it is shown how the community is succeeding in tailoring new technological solutions for a green transition, according with the specific needs of the island, as expressed by the islanders themselves, including batteries, electric vehicles, retrofitting of homes, or heat pumps, which, when combined, could lay the foundations for the creation of a Renewable Energy Community and leverage socioeconomic benefits. info:eu-repo/semantics/acceptedVersion