Tablet-based Augmented reality and 3D printed templates in fully guided Microtia Reconstruction: a clinical workflow.

BACKGROUND: Microtia is a congenital malformation of the auricle that affects approximately 4 of every 10,000 live newborns. Radiographic film paper is traditionally employed to bidimensionally trace the structures of the contralateral healthy ear in a quasi-artistic manner. Anatomical points provide linear and angular measurements. However, this technique proves time-consuming, subjectivity-rich, and greatly dependent on surgeon expertise. Hence, it's susceptible to shape errors and misplacement. METHODS: We present an innovative clinical workflow that combines 3D printing and augmented reality (AR) to increase objectivity and reproducibility of these procedures. Specifically, we introduce patient-specific 3D cutting templates and remodeling molds to carve and construct the cartilaginous framework that will conform the new ear. Moreover, we developed an in-house AR application compatible with any commercial Android tablet. It precisely guides the positioning of the new ear during surgery, ensuring symmetrical alignment with the healthy one and avoiding time-consuming intraoperative linear or angular measurements. Our solution was evaluated in one case, first with controlled experiments in a simulation scenario and finally during surgery. RESULTS: Overall, the ears placed in the simulation scenario had a mean absolute deviation of 2.2 ± 1.7 mm with respect to the reference plan. During the surgical intervention, the reconstructed ear was 3.1 mm longer and 1.3 mm wider with respect to the ideal plan and had a positioning error of 2.7 ± 2.4 mm relative to the contralateral side. Note that in this case, additional morphometric variations were induced from inflammation and other issues intended to be addressed in a subsequent stage of surgery, which are independent of our proposed solution. CONCLUSIONS: In this work we propose an innovative workflow that combines 3D printing and AR to improve ear reconstruction and positioning in microtia correction procedures. Our implementation in the surgical workflow showed good accuracy, empowering surgeons to attain consistent and objective outcomes.

Immune response to co-administration of measles, mumps, and rubella (MMR), and yellow fever vaccines: a randomized non-inferiority trial among one-year-old children in Argentina.

BACKGROUND: In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration. METHODS: We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR1YF1), MMR followed by YF vaccine four weeks later (MMR1YF2), or YF followed by MMR vaccine four weeks later (YF1MMR2). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests. RESULTS: Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR1YF1 group versus 96.3% in the MMR1YF2 group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR1YF1 versus 94.7% MMR1YF2, a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR1YF1 versus 97.9% MMR1YF2, a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR1YF1 versus 97.5% YF1MMR2, a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted. CONCLUSION: Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration. TRIAL REGISTRATION: The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017.

Reflections on the Biology of Cell Culture Models: Living on the Edge of Oxidative Metabolism in Cancer Cells.

Nowadays, the study of cell metabolism is a hot topic in cancer research. Many studies have used 2D conventional cell cultures for their simplicity and the facility to infer mechanisms. However, the limitations of bidimensional cell cultures to recreate architecture, mechanics, and cell communication between tumor cells and their environment, have forced the development of other more realistic in vitro methodologies. Therefore, the explosion of 3D culture techniques and the necessity to reduce animal experimentation to a minimum has attracted the attention of researchers in the field of cancer metabolism. Here, we revise the limitations of actual culture models and discuss the utility of several 3D culture techniques to resolve those limitations.

Stakeholder Perspectives on the Current and Future of Additive Manufacturing in Healthcare.

Additive manufacturing (AM) technologies have disrupted many supply chains by making new designs and functionalities possible. The opportunity to realize complex customized structures has led to significant interest within healthcare; however, full utilization critically requires the alignment of the whole supply chain. To offer insights into this process, a survey was conducted to understand the views of different medical AM stakeholders. The results highlighted an agreement between academics, designers, manufacturers, and medical experts, that personalization and design control are the main benefits of AM. Interestingly, surface finish was consistently identified as an obstacle. Nevertheless, there was a degree of acceptance that post-processing was necessary to achieve appropriate quality control. Recommendations were made for extending the use of in situ process monitoring systems to support improved reproducibility. Variations in the future vision of AM were highlighted between stakeholder groups and areas of interest for development noted for each stakeholder. Collectively, this survey indicates that medical stakeholders agree on the capabilities of AM but have different priorities for its implementation and progression. This highlights a degree of disconnection among the supply chain at a ground level; thus, collaboration on AM specific standards and enhancement of communication between stakeholders from project inception is recommended.

Endometriosis umbilical primaria: reporte de dos casos / Primary umbilical endometriosis: two case reports

INTRODUCCIÓN: La endometriosis es una patología benigna, dependiente de estrógenos, en la que el tejido que normalmente crece dentro del útero aparece fuera de este. Su localización habitual es en la pelvis, pero en ocasiones puede aparecer en otras áreas, como es el caso de la endometriosis umbilical. OBJETIVO: Familiarizar al ginecólogo con esta patología y entregar una serie de herramientas para diagnosticar, tratar y seguir a las pacientes que la presentan. CASOS CLÍNICOS: Se presentan dos casos clínicos de endometriosis umbilical primaria diagnosticados en el Hospital La Paz, en Madrid (España), entre los años 2018 y 2019. Las pacientes, de 30 y 34 años, consultaron por dolor o sangrado umbilical durante la menstruación. Ninguna tenía antecedentes de patología ginecológica ni cirugía abdominal previa. Tras una exhaustiva exploración física y una ecografía de alta resolución, se decidió extirpar la lesión con la colaboración del servicio de cirugía plástica. En ambos casos, el estudio anatomopatológico confirmó que se trataba de tejido endometriósico. Las dos pacientes presentaron una buena evolución posquirúrgica, sin recidivas hasta la fecha. CONCLUSIONES: La endometriosis umbilical primaria es una patología infrecuente, pero es necesario incluirla en el diagnóstico diferencial de una mujer con un nódulo umbilical. Siempre deben realizarse una exploración física exhaustiva y una ecografía ginecológica, para descartar posibles patologías concomitantes. El tratamiento de elección es la extirpación quirúrgica de la lesión y el diagnóstico final se establece con el estudio anatomopatológico.

INTRODUCTION: Endometriosis is an estrogen-dependent benign pathology in which endometrial tissue develops outside the uterus. Its most frequent location is the pelvis, although it can appear in other areas such as the umbilicum. OBJECTIVE: To familiarize the gynecologist with this pathology and provide a series of tools to diagnose, treat and provide continued care to these patients. CASE REPORTS: Retrospective study of two clinical cases of primary umbilical endometriosis diagnosed at La Paz University Hospital, in Madrid (Spain), between 2018 and 2019. Both patients (30 and 34 years old respectively) presented with pain and/or bleeding around the umbilical area during menstruation. Neither of them had any previous gynecologic conditions or abdominal surgeries. After exhaustive physical examination and a high-resolution ultrasound, lesions were surgically removed in collaboration with the plastic surgery department. In both cases, histology confirmed the presence of endometrial tissue. Both patients made a full recovery after surgery and havent had a recurrence of said lesions. CONCLUSIONS: Primary umbilical endometriosis is an infrequent disease. However, it must be included in the differential diagnosis of umbilical nodes in women. Exhaustive physical examination and gynecologic ultrasound should always be performed to rule out any other pathologies. Surgical removal of the nodes is the preferred treatment, and the final diagnosis is reached through histology.

Seasonal influenza vaccination policies in the 194 WHO Member States: The evolution of global influenza pandemic preparedness and the challenge of sustaining equitable vaccine access.

INTRODUCTION: As of 2018, 118 of 194 WHO Member States reported the presence of an influenza vaccination policy. Although influenza vaccination policies do not guarantee equitable access or ensure vaccination coverage, they are critical to establishing a coordinated influenza vaccination program, which can reduce morbidity and mortality associated with yearly influenza, especially in high-risk groups. Established programs can also provide a good foundation for pandemic preparedness and response. METHODS: We utilized EXCEL and STATA to evaluate changes to national seasonal influenza vaccination policies reported on the WHO/UNICEF Joint Reporting Forms on Immunization (JRF) in 2014 and 2018. To characterize countries with or without policies, we incorporated external data on World Bank income groupings, WHO regions, and immunization system strength (using 3 proxy indicators). RESULTS: From 2014 to 2018 there was a small net increase in national seasonal influenza vaccination policies from 114 (59%) to 118 (61%). There was an increase in policies targeting high-risk groups from 34 in 2014 (34 /114 policies, 29%) to 56 (56/118 policies, 47%) in 2018. Policies were consistently more frequent in high-income countries, in WHO Regions of the Americas (89% of countries) and Europe (89%), and in countries satisfying all three immunization system strength indicators. Low and low-middle income countries, representing 40% of the worlds' population, accounted for 52/61 (85%) of countries with no evidence of a policy in either year. CONCLUSION: Our results demonstrate that national influenza vaccination policies vary significantly by region, income, and immunization system strength, and are less common in lower-income countries. Barriers to establishing and maintaining policies should be further examined as part of international efforts to expand influenza vaccination policies globally. Next generation influenza vaccine development should work to address barriers to influenza vaccination policy adoption, such as cost, logistics for adult vaccination, country priorities, need for yearly vaccination, and variations in seasonality.

Adverse events associated with the use of recommended vaccines during pregnancy: An overview of systematic reviews.

INTRODUCTION: Maternal immunization is aimed at reducing morbidity and mortality in pregnant women and their newborns. Updated evidence synthesis of maternal-fetal outcomes is constantly needed to ensure that the risk-benefit of vaccination during pregnancy remains positive. METHODS: An overview of systematic reviews (OoSRs) was performed. We searched The Cochrane Library, MEDLINE and EMBASE for SRs including recommended vaccines for maternal immunization reporting the following: abortion, stillbirth, chorioamnionitis, congenital anomalies, microcephaly, neonatal death, neonatal infection, preterm birth (PTB), low birth weight (LBW), maternal death and small for gestational age (SGA) from 2010 to April 2019. Quality and overlap of SRs was assessed. RESULTS: Seventeen SRs were identified, eight of them included meta-analysis; quality was high in three SRs, moderate in six SRs, low in two SRs, and critically low in six SRs. Stillbirth and PTB were the most frequently reported outcomes by 15 and 13 SRs, respectively, followed by abortion (9 SRs), congenital anomalies (9 SRs), SGA (8 SRs), neonatal death (8 SRs), LBW (4 SRs), chorioamnionitis (3 SRs), maternal death (1 SR). SRs included mainly observational evidence for influenza and Tdap vaccines (11 SRs and 4 SRs, respectively); limited evidence was found for hepatitis (1 SR), yellow fever (1 SR), and meningococcal (1 SR) vaccines. Most of the SRs found no effect. Eight SRs found benefit/protection of influenza vaccine (for stillbirth, neonatal death, preterm birth, LBW), or Tdap vaccine (for preterm birth and SGA); one found a probable risk (chorioamnionitis/Tdap). The SRs for Hepatitis B, meningococcal and yellow fever vaccines were inconclusive. CONCLUSIONS: Definite risks were not identified for any vaccine and outcome; however better evidence is needed for all outcomes and vaccines. The available evidence in the SRs to support vaccine safety was based mainly on observational data. More RCTs with adequate reporting of maternal-fetal outcomes and larger high-quality observational studies are needed.

Enablers and barriers of maternal and neonatal immunization programs in Latin America.

BACKGROUND: The Region of the Americas has a long history of implementing maternal and neonatal immunization (MNI) programs. Our study aimed to understand the state of MNI policies, strategies and implementation practices in Latin America (LA). METHODS: Study conducted in 5 middle-income countries: Argentina, Brazil, Honduras, Mexico and Peru. The methods included a desk review, interviews with national stakeholders and health care providers, focus groups with pregnant women and observations in health facilities. Enablers and barriers were identified and categorized as individual, societal or related to the health system. RESULTS: All 5 participating countries had similar MNI policies and high access to antenatal care. Key enablers were the high acceptability of vaccination during pregnancy, high-level of political will and a national legal framework ensuring free access to vaccines. At the health system level, implementation was facilitated by the existence of immunization advisory committees, a pooled vaccine procurement mechanism, complementary vaccine delivery strategies, conditional cash transfer to users and performance incentives to health facilities. The main programmatic barriers were the lack of adequate MNI information; limited coordination between antenatal and immunization services; inadequate supply, resources and infrastructure; high staff turnover; insufficient training for health care providers; and weak monitoring and reporting systems. CONCLUSION: Middle-income countries in LA have successfully implemented MNI programs and several enablers were identified. To overcome remaining barriers, there is a need to focus on improving the "immunization journey" for pregnant women through providing more clear and timely information to users and providers; removing barriers to access; ensuring adequate supply, human resources and infrastructure; making the health service experience positive; and establishing integrated information systems that allow for monitoring the progress toward achieving MNI goals. Strengthening the MNI programs can also improve equitable access to health services and prepare for the introduction of future vaccines for pregnant women.

Seroprevalence of Varicella in Pregnant Women and Newborns in a Region of Colombia.

We estimate the seroprevalence of IgG antibodies to varicella zoster virus (VZV) based on the first serological study in a cohort of pregnant women and newborns from the Aburrá Valley (Antioquia-Colombia) who attended delivery in eight randomly chosen hospitals. An indirect enzyme immunoassay was used to determine anti-VZV IgG antibodies. Generalized linear models were constructed to identify variables that modify seropositivity. In pregnant women, seropositivity was 85.8% (95% CI: 83.4-85.9), seronegativity was 12.6% (95% CI: 10.8-14.6), and concordance with umbilical cord titers was 90.0% (95% CI: 89-91). The seropositivity of pregnant women was lower in those who lived in rural areas (IRR: 0.4, 95% CI: 0.2-0.7), belonged to the high socioeconomic status (IRR: 0.4, 95% CI: 0.2-0.7), and had studied 11 years or more (IRR: 0.6, 95% CI: 0.4-0.8). Among newborns, seropositivity was lower in those who weighed less than 3000 g (IRR: 0.8, 95% CI: 0.6-1.0). The high seropositivity and seronegativity pattern indicates the urgent need to design preconception consultation and vaccination reinforcement for women of childbearing age according to their sociodemographic conditions, to prevent infection and complications in the mother and newborn.

Computer-Assisted Dental Implant Placement Following Free Flap Reconstruction: Virtual Planning, CAD/CAM Templates, Dynamic Navigation and Augmented Reality.

Image-guided surgery, prosthetic-based virtual planning, 3D printing, and CAD/CAM technology are changing head and neck ablative and reconstructive surgical oncology. Due to quality-of-life improvement, dental implant rehabilitation could be considered in every patient treated with curative intent. Accurate implant placement is mandatory for prosthesis long-term stability and success in oncologic patients. We present a prospective study, with a novel workflow, comprising 11 patients reconstructed with free flaps and 56 osseointegrated implants placed in bone flaps or remnant jaws (iliac crest, fibula, radial forearm, anterolateral thigh). Starting from CT data and jaw plaster model scanning, virtual dental prosthesis was designed. Then prosthetically driven dental implacement was also virtually planned and transferred to the patient by means of intraoperative infrared optical navigation (first four patients), and a combination of conventional static teeth supported 3D-printed acrylic guide stent, intraoperative dynamic navigation, and augmented reality for final intraoperative verification (last 7 patients). Coronal, apical, and angular deviation between virtual surgical planning and final guided intraoperative position was measured on each implant. There is a clear learning curve for surgeons when applying guided methods. Initial only-navigated cases achieved low accuracy but were comparable to non-guided freehand positioning due to jig registration instability. Subsequent dynamic navigation cases combining highly stable acrylic static guides as reference and registration markers result in the highest accuracy with a 1-1.5-mm deviation at the insertion point. Smartphone-based augmented reality visualization is a valuable tool for intraoperative visualization and final verification, although it is still a difficult technique for guiding surgery. A fixed screw-retained ideal dental prosthesis was achieved in every case as virtually planned. Implant placement, the final step in free flap oncological reconstruction, could be accurately planned and placed with image-guided surgery, 3D printing, and CAD/CAM technology. The learning curve could be overcome with preclinical laboratory training, but virtually designed and 3D-printed tracer registration stability is crucial for accurate and predictable results. Applying these concepts to our difficult oncologic patient subgroup with deep anatomic alterations ended in comparable results as those reported in non-oncologic patients.

PIPDeploy: Development and implementation of a gamified table top simulation exercise to strengthen national pandemic vaccine preparedness and readiness.

Successful emergency vaccination campaigns rely on effective deployment and vaccination plans. This applies to localised outbreaks as well as for pandemics. In the wake of the 2009 H1N1 influenza pandemic, analysis of the global Vaccine Deployment Initiative, through which the World Health Organization (WHO) donated pandemic influenza vaccines to countries in need, revealed that an absence of vaccine deployment plans in many countries significantly hindered vaccine deployment. Through the Pandemic Influenza Preparedness Framework adopted by the World Health Assembly in 2011, WHO is engaging in several capacity building activities to improve pandemic influenza preparedness and response and make provisions for access to vaccines and sharing of other benefits. The Framework calls for the development and exercise of operational plans for deployment of influenza vaccines to enhance pandemic preparedness. To this end, WHO has supported the development of PIPDeploy, an interactive, in-person table top simulation exercise to facilitate learning for emergency preparedness. It employs various game design elements including a game board, time pressure, leaderboards and teams to enhance participants' motivation. PIPDeploy formed part of five WHO Pandemic Influenza Vaccine Deployment Workshops attended by national-level managers responsible for pandemic influenza vaccine response predominantly in non-producing countries. The purpose of this study was to describe the features and application of PIPDeploy, and present findings of the evaluation of participants' experiences during the simulation involving a "hot wash" discussion and collection of quantitative data. The simulation's instructional approach was widely accepted by participants, who reported that the format was novel and engaging. They reflected on its utility for identifying gaps in their own vaccine deployment plans and regulatory frameworks for importation of vaccine products. All participants found the simulation relevant to their professional objectives. A range of other potential applications were suggested, including PIPDeploy's adaptation to sub-national contexts and to other epidemic diseases.

Development and surgical application of a custom implant that enables a vertical vector of mandibular distraction.

Hemifacial microsomia is a congenital malformation that involves the underdevelopment of the mandible and the ear leading to facial asymmetry. Distraction osteogenesis is the gold standard surgical procedure for severe cases of hemifacial microsomia in which two sectioned bone parts are lengthened gradually to promote bony infill. The final shape of the bone depends on the position of the distractor and the vector of distraction. This article presents a complex clinical case of a 7-year-old patient with severe hemifacial microsomia that required distraction to correct mandibular asymmetry. Digital technology was applied to virtually plan the surgery pre-operatively. Optimal symmetrisation required a vertical vector of distraction that none of the 'off-the-shelf' distractors could provide. Consequently, a three-dimensional printed titanium implant was designed as a spacer to be attached to the inferior plate of a standard distractor, allowing the achievement of a vertical vector. By adding the spacer, the inferior footplate of the distractor was not directly fixed to bone and the vector of distraction was not dictated by the anatomical contour of the patient but by the shape of the spacer. Surgical guides were created to translate the virtual plan to the operating room. The guides prevented potential damage to tooth buds and the inferior alveolar nerve. This article describes the three-dimensional computer-aided design and additive manufacture of the custom devices that delivered the following: (1) symmetrisation of the mandible after distraction surgery without manipulation of the healthy side of the mandible; (2) a feasible and safer surgical solution; and (3) an innovative method that enables a wider range of vectors of distraction, bringing new prospects to the treatment of distraction osteogenesis in the future.

Dr. Daniel Inclán López: paradigma del servicio médico

Daniel Inclán López nació el 21 de julio de 1937, en Los Palacios, Pinar del Río. Cursó estudios primarios y de bachillerato en esa provincia hasta 1954. Ingresó en la Universidad de La Habana para estudiar Medicina. Se graduó en 1965. Participó en la lucha contra Batista. Perteneció al Movimiento Revolucionario 26 de Julio. Al triunfo de la Revolución, cumplió diversas tareas en las Fuerzas Armadas Revolucionarias: fue segundo Jefe de Servicios Médicos del Ejército de Oriente, desde 1966 a 1970, Jefe de la Sección de Prevención y Asistencia Médica de la Dirección de Servicios Médicos de las FAR. Cumplió misiones internacionalistas. Es fundador de la Asociación de Jóvenes Rebeldes (AJR) en La Universidad y del PCC. En 2000, le fue otorgado por el Ministro de Salud Pública el "Premio Anual de la Salud". Desde 2012 es profesor del Departamento de Preparación para la Defensa en la FCM "General Calixto García". De abril de 2014 a septiembre de 2017 dirigió ese Departamento. Por su labor docente, política y revolucionaria recibió diferentes reconocimientos.

Daniel Inclán López was born in July,1937 in a place called Los Palacios, Pinar del Río. He studied Elementary School and High School in that province until 1954. He began his medical studies in the University of Havana and completed them in 1965. Dr. Daniel Inclán participated in the fight against Batista. He was member of the Movimiento Revolucionario 26 de julio (MR26-7). After the triumph of the Revolution, he performed a variety of tasks within the Revolutionary Armed Forces: he was the second in command of the medical services of the arm forces in the Eastern region of the country (from 1966 to 1970) and the Head of the Sección de Prevención y Asistencia Médica de la Dirección de Servicios Médicos de las FAR. He participated in several internationalist missions. In the university, Dr. Inclán was the founder of the Asociación de Jóvenes Rebeldes (AJR) and the Partido Comunista de Cuba (PCC). In 2000, he received the "Premio Annual de Salud" award, which was given by the Ministry of Public Health. Since 2012, he has worked as professor of the Departamento de Preparación para la Defensa in "General Calixto Gracía" Medical Faculty. He was the head of this department from April 2014 to September 2017. He received many recognitions for his teaching, political, and revolutionary work.

Autotransplantation of a surgically removed canine using a customised 3D-printed surgical template.

Autotransplantation is a treatment option with high reported survival rates to replace failing teeth in the anterior maxilla. This treatment requires a multidisciplinary approach from orthodontists, paediatric dentists, restorative dentists, and oral and maxillofacial surgeons to achieve successful outcomes. Success is dependent on many factors including stage of root development, handling of the periodontal ligament, extra-alveolar time and splinting. This case report presents the novel use of digitally designed and three-dimensional (3D) printed surgical templates to aid intraoperatively and reduce the extra-alveolar time. A preoperative cone-beam computed tomography scan allowed digital planning and construction of surgical templates that replicated the exact root dimensions of impacted maxillary canines. These templates were subsequently 3D printed in resin, sterilised and utilised intraoperatively to aid socket preparation before the surgical autotransplantation.

Influenza vaccine effectiveness against hospitalizations in children and older adults-Data from South America, 2013-2017. A test negative design.

BACKGROUND: In 2013, the Pan American Health Organization established a multi-site, multi-country network to evaluate influenza vaccine effectiveness (VE). We pooled data from five consecutive seasons in five countries to conduct an analysis of southern hemisphere VE against laboratory-confirmed influenza hospitalizations in young children and older adults. METHODS: We used a test-negative design to estimate VE against laboratory-confirmed influenza in hospitalized young children (aged 6─24 months) and older adults (aged ≥60 years) in Argentina, Brazil, Chile, Colombia, and Paraguay. Following country-specific influenza surveillance protocol, hospitalized persons with severe acute respiratory infections (SARI) at 48 sentinel hospitals (March 2013-December 2017) were tested for influenza virus infection by rRT-PCR. VE was estimated for young children and older adults using logistic random effects models accounting for cluster (country), adjusting for sex, age (months for children, and age-in-year categories for adults), calendar year, country, preexisting conditions, month of illness onset and prior vaccination as an effect modifier for the analysis in adults. RESULTS: We included 8426 SARI cases (2389 children and 6037 adults) in the VE analyses. Among young children, VE against SARI hospitalization associated with any influenza virus was 43% (95%CI: 33%, 51%) for children who received two doses, but was 20% (95%CI: -16%, 45%) and not statistically significant for those who received one dose in a given season. Among older adults, overall VE against SARI hospitalization associated with any influenza virus was 41% (95%CI: 28%, 52%), 45% (95%CI: 34%, 53%) against A(H3N2), 40% (95%CI: 18%, 56%) against A(H1N1)pdm09, and 20% (95%CI: -40%, 54%) against influenza B viruses. CONCLUSIONS: Our results suggest that over the five-year study period, influenza vaccination programs in five South American countries prevented more than one-third of laboratory confirmed influenza-associated hospitalizations in young children receiving the recommended two doses and vaccinated older adults.

Fibromatosis mamaria. Reporte de dos casos clínicos y revisión bibliogáfica / Mammary fibromatosis. Two case report and review of literatura

RESUMEN Introducción y objetivos: La fibromatosis produce tumores benignos pero localmente agresivos, que afectan a los tejidos blandos. A nivel mamario, representa tan sólo el 0.2% de las neoplasias de la mama. Nuestro objetivo con el presente artículo es profundizar en el conocimiento de la fibromatosis mamaria, a través del estudio de dos casos clínicos, mostrando sus características clínico-radiológicas e histológicas, e intentar establecer un protocolo de actuación adecuado. Métodos: Estudio retrospectivo de dos casos clínicos de fibromatosis mamaria diagnosticados en el Hospital Universitario La Paz entre los años 2018 y 2019. Resultados: Presentaremos dos pacientes con diagnóstico de fibromatosis mamaria, ambas debutaron con la autopalpación de un nódulo mamario. Al realizarles una ecografía, se visualizó un nódulo sólido, mal definido y axila ecográficamente negativa, que precisó de biopsia-aspiración con aguja gruesa. En los dos casos, se decidió resección quirúrgica de la lesión. Seguimiento mediante exploración mamaria y pruebas de imagen periódicas. Conclusiones: Aunque se trata de una entidad benigna, la fibromatosis mamaria puede simular un proceso maligno, tanto clínica como radiológicamente, por lo que precisa de un estudio histológico. A pesar de que la diseminación metastásica es muy poco frecuente, no se debe olvidar el carácter agresivo a nivel local de esta patología, y sus altas tasas de recurrencia. Como tratamiento, se debe realizar una resección quirúrgica, aunque recientemente se ha contemplado la opción de vigilancia estrecha sin tratamiento. No existe evidencia científica que justifique la utilización de otros tratamientos como la radioterapia o el tratamiento hormonal.

ABSTRACT Introduction and objectives: Fibromatosis produces benign but locally aggressive tumours that affect soft tissues. At breast level, it represents only 0.2% of breast neoplasms. Our goal with this article is to increase knowledge on breast fibromatosis, through the study of two clinical cases; explaining their clinical-radiologic and histological characteristics. Additionally, try to establish an adequate protocol, for the management of the disease and for its subsequent monitoring. Methods: A retrospective study about two clinical cases of breast fibromatosis diagnosed in La Paz Hospital between 2018-2019. Results: both patients presented with clinical manifestations, autopalpation of a breast nodule. A breast ultrasound was performed and a solid nodule was visualized, with poorly defined edges and ecographically negative armpit. A core needle biopsy was performed to confirm the histological diagnosis. In both clinical cases, the treatment was surgical resection of the lesion. Periodic revisions are being performed in order to exclude recurrence. Conclusions: Although it is a benign disease, breast fibromatosis can simulate a malignancy, both in a clinical and radiological way, so histological study is mandatory in order to achieve an accurate diagnosis. Even metastatic dissemination is extremely rare, the local aggressive nature and high rates of recurrence for fibromatosis makes surgical excision, with wide free margins, the most important tool in treatment, although the possibility of close surveillance without treatment is recently being contemplated. There is no scientific evidence to justify the use of other treatments such as radiotherapy or hormonal treatment.

Introduction of new vaccines for immunization in pregnancy - Programmatic, regulatory, safety and ethical considerations.

Immunizing pregnant women is a promising strategy to reduce infectious disease-related morbidity and mortality in pregnant women and their infants. Important pre-requisites for the successful introduction of new vaccines for immunization in pregnancy include political commitment and adequate financial resources: trained, committed and sufficient numbers of healthcare workers to deliver the vaccines; close integration of immunization programs with antenatal care and Maternal and Child Health services; adequate access to antenatal care by pregnant women in the country (especially in low and middle-income countries (LMIC)); and a high proportion of births occurring in health facilities (to ensure maternal and neonatal follow-up can be done). The framework needed to advance a vaccine program from product licensure to successful country-level implementation includes establishing and organizing evidence for anticipated vaccine program impact, developing supportive policies, and translating policies into local action. International and national coordination efforts, proactive planning from conception to implementation of the programs (including country-level policy making, planning, and implementation, regulatory guidance, pharmacovigilance) and country-specific and cultural factors must be taken into account during the vaccines introduction.

The pluripotency factor NANOG controls primitive hematopoiesis and directly regulates Tal1.

Progenitors of the first hematopoietic cells in the mouse arise in the early embryo from Brachyury-positive multipotent cells in the posterior-proximal region of the epiblast, but the mechanisms that specify primitive blood cells are still largely unknown. Pluripotency factors maintain uncommitted cells of the blastocyst and embryonic stem cells in the pluripotent state. However, little is known about the role played by these factors during later development, despite being expressed in the postimplantation epiblast. Using a dual transgene system for controlled expression at postimplantation stages, we found that Nanog blocks primitive hematopoiesis in the gastrulating embryo, resulting in a loss of red blood cells and downregulation of erythropoietic genes. Accordingly, Nanog-deficient embryonic stem cells are prone to erythropoietic differentiation. Moreover, Nanog expression in adults prevents the maturation of erythroid cells. By analysis of previous data for NANOG binding during stem cell differentiation and CRISPR/Cas9 genome editing, we found that Tal1 is a direct NANOG target. Our results show that Nanog regulates primitive hematopoiesis by directly repressing critical erythroid lineage specifiers.

Design and material evaluation for a novel lumbar disc replacement implanted via unilateral transforaminal approach.

The degeneration of the intervertebral disc is one of the principal causes of low back pain. Total disc replacement is a surgical treatment that aims to replace the degenerated disc with a dynamic implant to restore spine biomechanics. This paper proposes the first design of an elastomeric lumbar disc replacement that is implanted as a pair of devices via unilateral transforaminal surgical approach. Furthermore, several biomaterials (Polyurethanes (PU) and Polycarbonate Urethanes (PCU)) are evaluated for the purpose of the implant to mimic the axial compliance of the spine. Bionate II 80A (a pure PCU), Elast Eon 82A E5-325 (a PU with polydimethylsiloxane and polyhexamethylene oxide), Chronosil (a PCU based silicone elastomer) 80A with 5% and 10% of silicone were obtained and injection moulded according to the shape of the implant core, which was defined after a stress distribution analysis with the finite element method. The dimensions for each specimen were: 14.6 × 5.6 × 6.1 mm (length, width and height). Quasistatic compression tests were performed at a displacement rate of 0.02 mm/s. The obtained stiffness for each material at 1 mm displacement was: Bionate II 80A, 448.48 N/mm; Elast Eon 82A E5-325, 216.55 N/mm; Chronosil 80A 5%, 127.73 N/mm; and Chronosil 80A 10%, 126.48 N/mm. Dimensional changes were quantified after two quasi-static compression tests. Plastic deformation was perceived in all cases with a total percentage of height loss of: 4.1 ±â€¯0.5% for Elast Eon 82A E5-325; 3.2 ±â€¯0.5% for Chronosil 80A 10%; 2.7 ±â€¯0.3% for Chronosil 80A 5% and 1.1 ±â€¯0.2% for Bionate II 80A. The mechanical behaviour of these biomaterials is discussed to assess their suitability for the novel disc replacement device proposed.