Anti-hemagglutinin monomeric nanobody provides prophylactic immunity against H1 subtype influenza A viruses.

Influenza viruses constitute a major threat to human health globally. The viral surface glycoprotein hemagglutinin (HA) is the immunodominant antigen, contains the site for binding to the cellular receptor (RBS), and it is the major target of neutralizing antibody responses post-infection. We developed llama-derived single chain antibody fragments (VHHs) specific for type A influenza virus. Four VHHs were identified and further characterized. VHH D81 bound residues in the proximity of the C-terminal region of HA1 of H1 and H5 subtypes, and showed weak neutralizing activity, whereas VHH B33 bound residues in the proximity of the N-terminal region of the HA's stem domain (HA2) of H1, H5, and H9 subtypes, and showed no neutralizing activity. Of most relevance, VHHs E13 and G41 recognized highly conserved conformational epitopes on the H1 HA's globular domain (HA1) and showed high virus neutralizing activity (ranging between 0.94 to 0.01µM), when tested against several human H1N1 isolates. Additionally, E13 displayed abrogated virus replication of a panel of H1N1 strains spanning over 80 years of antigenic drift and isolated from human, avian, and swine origin. Interestingly, E13 conferred protection in vivo at a dose as low as 0.05 mg/kg. Mice treated with E13 intranasally resulted in undetectable virus challenge loads in the lungs at day 4 post-challenge. The transfer of sterilizing pan-H1 immunity, by a dose in the range of micrograms given intranasally, is of major significance for a monomeric VHH and supports the further development of E13 as an immunotherapeutic agent for the mitigation of influenza infections.

Risk factors for colonisation by Multidrug-Resistant bacteria in critical care units.

INTRODUCTION: Antimicrobial resistance is a major public health challenge recognised by the WHO as an urgent global healthcare concern. Patients in Intensive Care Units (ICUs) are particularly prone to colonisation and/or infection by multidrug-resistant organisms (MDROs). OBJECTIVES: Delineate the epidemiological characteristics and risk factors for MDROs colonisation in mixed ICUs and Resuscitation Units by focusing on initial and nosocomial colonisation. MATERIAL AND METHODS: A descriptive observational study with analytical elements. It uses the Zero-Resistance register from the Preventive Medicine Service of the Albacete General University Hospital (Spain) from April 2016 to December 2021. It identifies the risk factors for MDROs colonisation. RESULTS: Of 7,541 cases, 61.0 % with initial colonisation had risk factors for MDROs versus 34.0 % not colonised upon hospitalisation (p < 0.001). Significant risk factors for initial colonisation included hospitalisation for ≥ 5 days within the last 3 months, prior MDROs colonisation/infection and institutionalization. No significant risk factor differences were found for nosocomial colonisation. An association between longer ICU stays and nosocomial colonisation (p < 0.001) was noted. CONCLUSIONS: Significant risk factors for initial MDROs colonisation were hospitalisation for ≥ 5 days in the last 3 months, prior MDROs colonisation/infection and institutionalisation. Longer ICU stays increased the nosocomial colonisation risk. IMPLICATIONS FOR CLINICAL PRACTICE: This study underscores the importance to early identify and manage patients at risk for MDROs colonisation in ICUs. By recognising factors (i.e. previous hospitalisations, existing colonisation or infection, impact of prolonged ICU stay), healthcare providers can implement targeted strategies to mitigate the spread of MDROs; e.g. enhanced surveillance, stringent infection control measures and judicious antibiotics use. Our findings highlight the need for a comprehensive approach to manage antimicrobial resistance in critical care settings to ultimately improve patient outcomes and reduce MDROs burden in hospitals.

Enhanced Recombinant Protein Expression in Insect Cells by Natural and Recombinant Components of Lepidoptera Hemolymph.

Prior research has established the anti-apoptotic effects in insect cell cultures of Bombyx mori (B. mori) hemolymph, as well as the heightened production yields of recombinant proteins facilitated by baculovirus vectors in insect cells cultivated in media supplemented with this hemolymph. In this study, we investigated the hemolymph of another Lepidoptera species, Trichoplusia ni (T. ni), and observed similar beneficial effects in insect cells cultivated in media supplemented with this natural substance. We observed enhancements in both production yield (approximately 1.5 times higher) and late-stage cell viabilities post-infection (30-40% higher). Storage-protein 2 from B. mori (SP2Bm) has previously been identified as one of the abundant hemolymph proteins potentially responsible for the beneficial effects observed after the use of B. mori hemolymph-supplemented cell culture media. By employing a dual baculovirus vector that co-expresses the SP2Bm protein alongside the GFP protein, we achieved a threefold increase in reporter protein production compared to a baculovirus vector expressing GFP alone. This study underscores the potential of hemolymph proteins sourced from various Lepidoptera species as biotechnological tools to augment baculovirus vector productivities, whether utilized as natural supplements in cell culture media or as hemolymph-derived recombinant proteins co-expressed by baculovirus vectors.

Development of a Fully Protective Pandemic Avian Influenza Subunit Vaccine in Insect Pupae.

In this study, we pioneered an alternative technology for manufacturing subunit influenza hemagglutinin (HA)-based vaccines. This innovative method involves harnessing the pupae of the Lepidoptera Trichoplusia ni (T. ni) as natural biofactories in combination with baculovirus vectors (using CrisBio® technology). We engineered recombinant baculoviruses encoding two versions of the HA protein (trimeric or monomeric) derived from a pandemic avian H7N1 virus A strain (A/chicken/Italy/5093/99). These were then used to infect T. ni pupae, resulting in the production of the desired recombinant antigens. The obtained HA proteins were purified using affinity chromatography, consistently yielding approximately 75 mg/L of insect extract. The vaccine antigen effectively immunized poultry, which were subsequently challenged with a virulent H7N1 avian influenza virus. Following infection, all vaccinated animals survived without displaying any clinical symptoms, while none of the mock-vaccinated control animals survived. The CrisBio®-derived antigens induced high titers of HA-specific antibodies in the vaccinated poultry, demonstrating hemagglutination inhibition activity against avian H7N1 and human H7N9 viruses. These results suggest that the CrisBio® technology platform has the potential to address major industry challenges associated with producing recombinant influenza subunit vaccines, such as enhancing production yields, scalability, and the speed of development, facilitating the global deployment of highly effective influenza vaccines.

Using the AS04C-adjuvanted hepatitis B vaccine in patients classified as non-responders.

BACKGROUND: Chronic hepatitis B (HB) remains a significant global health concern, despite the widespread availability of the HB vaccine. While the standard vaccine demonstrates an impressive serological response rate exceeding 90%, a subset of individuals exhibit suboptimal immunity. This study aims to elucidate the efficacy of the AS04C-adjuvanted HB vaccine in addressing non-responsiveness. METHODS: Conducted at the Preventive Medicine Service of the University Albacete Hospital in Spain from 2017 to 2021, this single-center observational study enrolled 195 patients. Among them, 126 (65%) were classified as non-responders following one or two complete standard vaccination courses. RESULTS: After the administration of a complete four-dose regimen of the AS04C-adjuvanted vaccine, 73.81% of non-responder patients exhibited antibody titers indicative of robust immunity (anti-HBs >10). CONCLUSIONS: These findings underscore the pivotal role of the AS04C-adjuvanted HB vaccine in addressing non-responsiveness, emphasizing its potential as a crucial tool in augmenting immunization strategies for various populations. This includes non-responders to standard vaccination, individuals with chronic kidney disease, those requiring seroprotection due to factors like immunosuppression or occupational hazards, as well as patients for whom conventional revaccination strategies have proven futile. Additional research is needed to expand on the promising results obtained through our protocol.

[Multiple PCR ALLPLEX TM ENTERO-DR for multidrug-resistant Enterobacteriaceae management at Albacete University Hospital]. / Aplicación de la PCR múltiple ALLPLEX TM ENTERO-DR en un protocolo de aislamiento por enterobacterias multirresistentes en el Complejo Hospitalario Universitario de Albacete.

OBJECTIVE: Multi-resistant Enterobacteriaceae (MRE) are a public health threat, with screening and isolation strategies being important to stop its dissemination. Multiplex PCR is a novel method capable of rapid diagnosis with high sensitivity and specificity. In this study, our objective was to evaluate its application to multidrug-resistant Enterobacteriaceae management since its implementation in our hospital. METHODS: An observational retrospective descriptive study of multiplex PCR ALLPLEX TM ENTERO-DR results to screen inpatients colonized by MRE took place from November 2019 to May 2021. We calculated the percentage of positive, negative, non-identifiable or invalid results, identified microorganisms, reason for requesting it and subsequent actions. Median and I.R. from sampling time to partial and theoretical culture time, and since last colonization/infection depending on test results were calculated. RESULTS: Resistance mechanisms were detected in 31.47% of tests, being E. coli ESBL (68.99%) the most frequently isolated microorganism. Median time to partial result was 5.75 hours (I.R.: 2.67), having statistically significant differences with theoretical time. The most important reason to request the test was screening (80.12%) and the most frequent action taken was not to isolate (41.70 %). Whenever forty-nine months or more since last colonization/infection have passed, only 14.81% of the samples tested positive. CONCLUSIONS: Multiplex PCR is a useful test to manage colonized patients, capable of giving a rapid result and allowing for quicker decision-making, contributing to a good use of resources and patient comfort.

OBJECTIVE: Las enterobacterias multirresistentes (EBMR) suponen una amenaza para la Salud Pública, siendo el cribado y aislamiento de pacientes colonizados importante para evitar su diseminación. La PCR múltiple es una técnica novedosa, capaz de proporcionar un diagnóstico rápido con sensibilidad y especificidad altas. El objetivo de este trabajo fue evaluar la aplicación de PCR múltiple en el protocolo de aislamiento por EBMR desde su implantación en nuestro centro. METHODS: Se realizó un estudio observacional descriptivo y retrospectivo. Se analizaron los resultados del estudio de colonización por EBMR a pacientes hospitalizados, mediante PCR múltiple ALLPLEX TM ENTERO-DR, entre noviembre de 2019 y mayo de 2021. Se calcularon las frecuencias de resultado positivo, negativo, no interpretable o inválido, de microorganismos identificados, el motivo de petición y actuación posterior. Se calcularon la mediana y Rango Intercuartílico (R.I.) del tiempo desde el cribado hasta el resultado parcial y final. También se calcularon la mediana y R.I. desde el antecedente de colonización/infección según resultado de la prueba rápida. RESULTS: Se detectó mecanismo de resistencia en el 31,47% de las pruebas, siendo más frecuentemente aislado E. coli BLEE (68,99%). La mediana de tiempo hasta el resultado parcial fue de 5,75 horas (R.I.: 2,67), existiendo diferencias estadísticamente significativas con el tiempo de cultivo teórico. El motivo principal de petición fue cribado por antecedente (80,12%) y la actuación más frecuente fue no aislar (41,70%). El 14,81% de las pruebas fue positivo si el antecedente de infección/colonización era mayor a cuarenta y nueve meses. CONCLUSIONS: La PCR múltiple es una prueba útil para el control de la colonización por EBMR, que disminuye el tiempo hasta resultado y facilita la toma de decisiones rápidas, pudiendo contribuir a la adecuada gestión de recursos y comodidad de pacientes.

Aplicación de la PCR múltiple ALLPLEX TM ENTERO-DR en un protocolo de aislamiento por enterobacterias multirresistentes en el Complejo Hospitalario Universitario de Albacete / Multiple PCR ALLPLEX TM ENTERO-DR for multidrug- resistant Enterobacteriaceae management at Albacete University Hospita

Fundamentos: Las enterobacterias multirresistentes (EBMR) suponen una amenaza para la Salud Pública, siendo el cribado y aislamiento de pacientes colonizados importante para evitar su diseminación. La PCR múltiple es una técnica novedosa, capaz de proporcionar un diagnóstico rápido con sensibilidad y especificidad altas. El objetivo de este trabajo fue evaluar la aplicación de PCR múltiple en el protocolo de aislamiento por EBMR desde su implantación en nuestro centro. Métodos: Se realizó un estudio observacional descriptivo y retrospectivo. Se analizaron los resultados del estudio de colonización por EBMR a pacientes hospitalizados, mediante PCR múltiple ALLPLEX TM ENTERO-DR, entre noviembre de 2019 y mayo de2021. Se calcularon las frecuencias de resultado positivo, negativo, no interpretable o inválido, de microorganismos identificados, el motivo de petición y actuación posterior. Se calcularon la mediana y Rango Intercuartílico (R.I.) del tiempo desde el cribado hasta el resultado parcial y final. También se calcularon la mediana y R.I. desde el antecedente de colonización/infección según resultado de la prueba rápida. Resultados: Se detectó mecanismo de resistencia en el 31,47% de las pruebas, siendo más frecuentemente aislado E. coli BLEE (68,99%). La mediana de tiempo hasta el resultado parcial fue de 5,75 horas (R.I.: 2,67), existiendo diferencias estadísticamente significativas con el tiempo de cultivo teórico. El motivo principal de petición fue cribado por antecedente (80,12%) y la actuación más frecuente fue no aislar (41,70%). El 14,81% de las pruebas fue positivo si el antecedente de infección/colonización era mayor a cuarenta y nueve meses. Conclusiones: La PCR múltiple es una prueba útil para el control de la colonización por EBMR, que disminuye el tiempo hasta resultado y facilita la toma de decisiones rápidas, pudiendo contribuir a la adecuada gestión de recursos y comodidad de pacientes.(AU)

Background: Multi-resistant Enterobacteriaceae (MRE) are a public health threat, with screening and isolation strategies beingimportant to stop its dissemination. Multiplex PCR is a novel method capable of rapid diagnosis with high sensitivity and specificity. In this study, our objective was to evaluate its application to multidrug-resistant Enterobacteriaceae management since its implementation in our hospital. Methods: An observational retrospective descriptive study of multiplex PCR ALLPLEX TM ENTERO-DR results to screen inpatients colonized by MRE took place from November 2019 to May 2021. We calculated the percentage of positive, negative, non-identifiable or invalid results, identified microorganisms, reason for requesting it and subsequent actions. Median and I.R. from sampling time to partial and theoretical culture time, and since last colonization/infection depending on test results were calculated. Results: Resistance mechanisms were detected in 31.47% of tests, being E. coli ESBL (68.99%) the most frequently isolated microorganism. Median time to partial result was 5.75 hours (I.R.: 2.67), having statistically significant differences with theoretical time. The most important reason to request the test was screening (80.12%) and the most frequent action taken was not to isolate (41.70 %). Whenever forty-nine months or more since last colonization/infection have passed, only 14.81% of the samples tested positive. Conclusions: Multiplex PCR is a useful test to manage colonized patients, capable of giving a rapid result and allowing for quicker decision-making, contributing to a good use of resources and patient comfort.(AU)

First wave of the COVID-19 pandemic in Madrid: handling the unexpected in a tertiary hospital.

Introduction: The COVID-19 pandemic was declared on March 11th, 2020. By the end of January, the first imported cases were detected in Spain and, by March, the number of cases was growing exponentially, causing the implementation of a national lockdown. Madrid has been one of the most affected regions in terms of both cases and deaths. The aim of this study is to describe the epidemic curve and the epidemiological features and outcomes of COVID-19 patients hospitalized in La Paz University Hospital, a tertiary hospital located in Madrid. Methods: We included confirmed and probable COVID-19 cases admitted to our centre from February 26th to June 1st, 2020. We studied trends in hospitalization and ICU admissions using joinpoint regression analysis. Results: A sample of 2970 patients was obtained. Median age was 70 years old (IQR 55-82) and 54.8% of them were male. ICU admission rate was 8.7% with a mortality rate of 45.7%. Global CFR was 21.8%. Median time from symptom onset to death was 14 days (IQR 9-22). Conclusions: We detected an admissions peak on March 21st followed by a descending trend, matching national and regional data. Age and sex distribution were comparable to further series nationally and in western countries.

Recomendaciones sobre el uso de la telemedicina aplicada a la patología nutricional / Recommendations on the use of telemedicine as applied to nutritional pathology

Introducción: la telemedicina puede mejorar la calidad asistencial y el uso de recursos. La pandemia de COVID-19 ha hecho necesaria su implementación en la práctica habitual. Por ello, un grupo de endocrinólogos de la Comunidad Valenciana, Murcia y Baleares creó un comité para su desarrollo. Objetivos: establecer unas recomendaciones para mejorar la calidad de la consulta de patología nutricional y diseñar unos indicadores para su gestión. Metodología: se siguió la metodología Delphi con participación de 13 profesionales con el fin de alcanzar el mayor consenso. Para ello se circuló un cuestionario de 16 puntos en 3 rondas: en la primera se estableció el grado de consenso; en la segunda, los participantes tuvieron acceso a los resultados de la primera y respondieron a las cuestiones planteadas. Se consideró que había acuerdo si el consenso era ≥ 75 % de los participantes, y que existía acuerdo fuerte si este era ≥ 90 %. Además, se estableció la temática de los indicadores de calidad. En la tercera se desarrollaron dichos indicadores. Resultados: tras 3 rondas y una reunión de revisión se establecieron los sobre aspectos organizativos 5 recomendaciones con acuerdo fuerte; sobre los aspectos administrativos, 6 recomendaciones con acuerdo fuerte y 4 con acuerdo. Se seleccionaron 8 indicadores de calidad que se desarrollaron en formato de fichas. Conclusiones: este documento recopila una serie de recomendaciones sobre cuestiones, necesidades y requisitos a tener en cuenta para una consulta telemática de calidad al paciente con patología nutricional. Así mismo, se han desarrollado unos indicadores para mejorar la calidad asistencial (AU)

Introduction: telemedicine can improve the standards of clinical care and use of resources. The COVID-19 pandemic has required its implementation in routine practice. For this reason, a group of endocrinologists from Valencia, Murcia and the Balearic Islands created a committee for its development. Objectives: to establish recommendations in order to improve the quality of consultation in nutritional disorders, and to create indicators for its management. Methodology: the Delphi methodology was followed with the participation of 13 professionals in order to reach the widest consensus. A 16-item questionnaire was distributed within 3 rounds: in the first round, the degree of consensus was established; in the second round, the participants responded to the posed questions after having access to the first-round results. Agreement was considered if ≥ 75 % participants reached consensus, while strong agreement was considered if consensus was reached by ≥ 90 %. In addition, quality indicators were established. In a third round, these indicators were developed. Results: after 3 rounds and a revision 5 recommendations with strong agreement were established based on organizational aspects. Regarding administrative aspects, 6 recommendations with strong agreement were established while 4 recommendations reached the level of agreement. Eight quality indicators were selected and developed. Conclusions this document compiles a list of recommendations about needs and requirements to be taken into account for a quality telematic consultation in patients with nutritional disorders. In addition, health care quality indicators have been created and developed (AU)

Clinical efficacy of urea treatment in syndrome of inappropriate antidiuretic hormone secretion.

The aim of this work is to examine our experience in the use of urea in patients with SIADH. Observational retrospective analysis of 48 patients with SIADH that have been treated with urea in a third-level hospital. Pre-post analysis of serum sodium levels. The 48 patients with SIADH had a median age of 78.5 (range 26-97 years). The serum sodium nadir was 119.8 ± 5.0 mmoL/L and at the beginning of treatment 125.6 ± 4.1 mmoL/L. The patients continued the treatment for a mean time of 2.95 ± 6.29 months, being the treatment still active in 4 patients. In all patients there was an improvement in serum sodium, being the final serum sodium at the end of treatment 134.4 ± 4.9 mmoL/L (p < 0.01). This improvement was observed from the first week. Adverse events were only detected in 2 patients with mild digestive symptomatology and 2 patients refused the treatment due to the low palatability of the urea. There was an economic cost reduction of 87.9% in comparison with treatment with tolvaptan. Urea has shown to be a safe and cost-effective option for the treatment of hyponatremia caused by SIADH.

[Recommendations on the use of telemedicine as applied to nutritional pathology]. / Recomendaciones sobre el uso de la telemedicina aplicada a la patología nutricional.

Introduction: Introduction: telemedicine can improve the standards of clinical care and use of resources. The COVID-19 pandemic has required its implementation in routine practice. For this reason, a group of endocrinologists from Valencia, Murcia and the Balearic Islands created a committee for its development. Objectives: to establish recommendations in order to improve the quality of consultation in nutritional disorders, and to create indicators for its management. Methodology: the Delphi methodology was followed with the participation of 13 professionals in order to reach the widest consensus. A 16-item questionnaire was distributed within 3 rounds: in the first round, the degree of consensus was established; in the second round, the participants responded to the posed questions after having access to the first-round results. Agreement was considered if ≥ 75 % participants reached consensus, while strong agreement was considered if consensus was reached by ≥ 90 %. In addition, quality indicators were established. In a third round, these indicators were developed. Results: after 3 rounds and a revision 5 recommendations with strong agreement were established based on organizational aspects. Regarding administrative aspects, 6 recommendations with strong agreement were established while 4 recommendations reached the level of agreement. Eight quality indicators were selected and developed. Conclusions: this document compiles a list of recommendations about needs and requirements to be taken into account for a quality telematic consultation in patients with nutritional disorders. In addition, health care quality indicators have been created and developed.

Introducción: Introducción: la telemedicina puede mejorar la calidad asistencial y el uso de recursos. La pandemia de COVID-19 ha hecho necesaria su implementación en la práctica habitual. Por ello, un grupo de endocrinólogos de la Comunidad Valenciana, Murcia y Baleares creó un comité para su desarrollo. Objetivos: establecer unas recomendaciones para mejorar la calidad de la consulta de patología nutricional y diseñar unos indicadores para su gestión. Metodología: se siguió la metodología Delphi con participación de 13 profesionales con el fin de alcanzar el mayor consenso. Para ello se circuló un cuestionario de 16 puntos en 3 rondas: en la primera se estableció el grado de consenso; en la segunda, los participantes tuvieron acceso a los resultados de la primera y respondieron a las cuestiones planteadas. Se consideró que había acuerdo si el consenso era ≥ 75 % de los participantes, y que existía acuerdo fuerte si este era ≥ 90 %. Además, se estableció la temática de los indicadores de calidad. En la tercera se desarrollaron dichos indicadores. Resultados: tras 3 rondas y una reunión de revisión se establecieron los sobre aspectos organizativos 5 recomendaciones con acuerdo fuerte; sobre los aspectos administrativos, 6 recomendaciones con acuerdo fuerte y 4 con acuerdo. Se seleccionaron 8 indicadores de calidad que se desarrollaron en formato de fichas. Conclusiones: este documento recopila una serie de recomendaciones sobre cuestiones, necesidades y requisitos a tener en cuenta para una consulta telemática de calidad al paciente con patología nutricional. Así mismo, se han desarrollado unos indicadores para mejorar la calidad asistencial.

Major bleeding in patients with pulmonary embolism presenting with syncope.

INTRODUCTION: Syncope has been shown to be a risk factor of bleeding in patients receiving thrombolytic therapy for acute pulmonary embolism (PE). Whether syncope predicts bleeding in a broader population of patients with PE remains unknown. METHODS: We used the RIETE registry data to assess whether initial presentation with syncope could predict bleeding in PE patients receiving anticoagulant therapy, and to explore the association between presence of syncope and timing and site of major bleeding events. RESULTS: Among 45,765 patients with acute PE from March 2001 to January 2021, 6760 (14.8%) had syncope. Patients with syncope were older and more likely to have hypotension, tachycardia, hypoxaemia or elevated troponin levels than those without syncope. They also were more likely to receive thrombolytics. During the first 90 days, 1097 patients (2.4%) suffered major bleeding (gastrointestinal 335, hematoma 271 and intracranial 163) and 3611 died (158 had fatal bleeding). Patients with syncope had a higher rate of major bleeding (odds ratio [OR]: 1.63; 95% CI: 1.41-1.89) and a nonsignificantly higher rate of fatal bleeding (OR: 1.47; 95% CI: 0.99-2.17) than those without syncope. Multivariable analysis confirmed that patients with syncope were at increased risk for major bleeding (adjusted hazard ratio [aHR]: 1.34; 95% CI: 1.15-1.55). On sensitivity analysis, the increased risk for major bleeding was confirmed in patients initially receiving anticoagulant therapy without thrombolytics at 7 days (aHR: 1.47; 95% CI: 1.13-1.91) and 90 days (aHR: 1.33; 95%CI: 1.13-1.56). DISCUSSION: Syncope is a predictor of major bleeding events in patients with PE, even among those receiving anticoagulation monotherapy.

[Vaccination against hepatitis B in patients with inflammatory bowel disease: immune response and associated factors.] / Vacunación frente a hepatitis B en pacientes con enfermedad inflamatoria intestinal: respuesta inmunitaria y factores asociados.

OBJECTIVE: Patients with Inflammatory Bowel Disease (IBD) are at increased risk of hepatitis B virus (HBV) infection as well as a lower response to vaccination. This study aimed to analyze the immune response after vaccination against HBV in patients diagnosed with IBD and its associated factors. METHODS: A retrospective observational study was conducted on patients with IBD treated at the vaccination clinic for at-risk patients at the Complejo Hospitalario Universitario de Albacete during the period 2011-2018. Immune response after vaccination and associated factors were determined using logistic regression models. RESULTS: 231 patients were included. HBV Vaccination had an optimal immune response in 82.7% of the patients. The likelihood of response to vaccination increased in those diagnosed with ulcerative colitis (OR 2.90; 95% CI 1.11-7.61) and decreased with age (80% lower in those aged 40-55 years (OR 0.20; 95% CI 0.05-0.83) and 88% lower in those over 55 years of age (OR 0.12; 95% CI 0.03-0.53) compared to those under 40 years of age) and pharmacological immunosuppression (OR 0.20; 95% CI 0.58-0.71). CONCLUSIONS: The decrease in the immunogenicity of the vaccine against hepatitis B in patients with IBD after the beginning of immunosuppressive treatment, as well as with age, make early vaccination a priority in this kind of patients.

OBJETIVO: Los pacientes con Enfermedad Inflamatoria Intestinal (EII) tienen más riesgo de infección por el virus de la hepatitis B (VHB) así como menor respuesta frente a la vacunación. El objetivo de este estudio fue analizar la respuesta inmunitaria tras la vacunación frente al VHB en los pacientes diagnosticados de EII y sus factores asociados. METODOS: Se realizó un estudio observacional retrospectivo sobre los pacientes con EII atendidos en la consulta de vacunas de pacientes de riesgo en el Complejo Hospitalario Universitario de Albacete durante el período 2011-2018. Se determinó la respuesta serológica tras la vacunación y los factores asociados mediante modelos de regresión logística. RESULTADOS: Se incluyeron 231 pacientes. La vacunación frente al VHB tuvo una respuesta inmunitaria óptima en un 82,7% de los pacientes. La probabilidad de respuesta a la vacunación aumentó en aquellos diagnosticados de colitis ulcerosa (OR 2,90; IC95% 1,11-7,61) y se redujo con la edad (80% menor en los de 40-55 años (OR 0,20; IC95% 0,05-0,83) y 88% menor en mayores de 55 años (OR 0,12; IC95% 0,03-0,53) frente a los menores de 40 años) y con la inmunosupresión farmacológica (OR 0,20; IC95% 0,58-0,71). CONCLUSIONES: La disminución de la inmunogenicidad de la vacuna frente a la hepatitis B en los pacientes con EII tras el inicio del tratamiento inmunosupresor, así como con la edad, hacen prioritaria la vacunación temprana en este tipo de pacientes.

Semi-supervised incremental learning with few examples for discovering medical association rules.

BACKGROUND: Association Rules are one of the main ways to represent structural patterns underlying raw data. They represent dependencies between sets of observations contained in the data. The associations established by these rules are very useful in the medical domain, for example in the predictive health field. Classic algorithms for association rule mining give rise to huge amounts of possible rules that should be filtered in order to select those most likely to be true. Most of the proposed techniques for these tasks are unsupervised. However, the accuracy provided by unsupervised systems is limited. Conversely, resorting to annotated data for training supervised systems is expensive and time-consuming. The purpose of this research is to design a new semi-supervised algorithm that performs like supervised algorithms but uses an affordable amount of training data. METHODS: In this work we propose a new semi-supervised data mining model that combines unsupervised techniques (Fisher's exact test) with limited supervision. Starting with a small seed of annotated data, the model improves results (F-measure) obtained, using a fully supervised system (standard supervised ML algorithms). The idea is based on utilising the agreement between the predictions of the supervised system and those of the unsupervised techniques in a series of iterative steps. RESULTS: The new semi-supervised ML algorithm improves the results of supervised algorithms computed using the F-measure in the task of mining medical association rules, but training with an affordable amount of manually annotated data. CONCLUSIONS: Using a small amount of annotated data (which is easily achievable) leads to results similar to those of a supervised system. The proposal may be an important step for the practical development of techniques for mining association rules and generating new valuable scientific medical knowledge.

Vacunación frente a hepatitis B en pacientes con enfermedad inflamatoria intestinal: respuesta inmunitaria y factores asociados / Vaccination against hepatitis B in patients with inflammatory bowel disease: immune response and associated factors

Fundamentos: Los pacientes con Enfermedad Inflamatoria Intestinal (EII) tienen más riesgo de infección por el virus de la hepatitis B (VHB) así como menor respuesta frente a la vacunación. El objetivo de este estudio fue analizar la respuesta inmunitaria tras la vacunación frente al VHB en los pacientes diagnosticados de EII y sus factores asociados. Métodos: Se realizó un estudio observacional retrospectivo sobre los pacientes con EII atendidos en la consulta de vacunas de pacientes de riesgo en el Complejo Hospitalario Universitario de Albacete durante el período 2011-2018. Se determinó la respuesta serológica tras la vacunación y los factoresasociados mediante modelos de regresión logística. Resultados: Se incluyeron 231 pacientes. La vacunación frente al VHB tuvo una respuesta inmunitaria óptima en un 82,7% de los pacientes. La probabilidad de respuesta a la vacunación aumentó en aquellos diagnosticados de colitis ulcerosa (OR 2,90; IC95% 1,11-7,61) y se redujo con la edad (80% menor en los de 40-55 años (OR 0,20; IC95% 0,05-0,83) y 88% menor en mayores de 55 años (OR 0,12; IC95% 0,03-0,53) frente a los menores de 40 años) y con la inmunosupresión farmacológica (OR 0,20; IC95% 0,58-0,71). Conclusiones: La disminución de la inmunogenicidad de la vacuna frente a la hepatitis B en los pacientes con EII tras el inicio del tratamiento inmunosupresor, así como con la edad, hacen prioritaria la vacunación temprana en este tipo de pacientes.(AU)

Background: Patients with Inflammatory Bowel Disease (IBD) are at increased risk of hepatitis B virus (HBV) infection as well as a lower response to vaccination. This study aimed to analyze the immune response after vaccination against HBV in patients diagnosed with IBD and its associated factors. Methods: A retrospective observational study was conducted on patients with IBD treated at the vaccination clinic for at-risk patients at the Complejo Hospitalario Universitario de Albacete during the period 2011-2018. Immune response after vaccination and associated factors were determined using logistic regression models. Results: 231 patients were included. HBV Vaccination had an optimal immune response in 82.7% of the patients. The likelihood of response to vaccination increased in those diagnosed with ulcerative colitis (OR 2.90; 95% CI 1.11-7.61) and decreased with age (80% lower in those aged 40- 55 years (OR 0.20; 95% CI 0.05-0.83) and 88% lower in those over 55 years of age (OR 0.12; 95% CI 0.03-0.53) compared to those under 40 years of age) and pharmacological immunosuppression (OR 0.20; 95% CI 0.58-0.71). Conclusions: The decrease in the immunogenicity of the vaccine against hepatitis B in patients with IBD after the beginning of immunosuppressive treatment, as well as with age, make early vaccination a priority in this kind of patients.(AU)

CHIVA method for the treatment of chronic venous insufficiency.

BACKGROUND: Many surgical approaches are available to treat varicose veins secondary to chronic venous insufficiency. One of the least invasive techniques is the ambulatory conservative hemodynamic correction of venous insufficiency method (in French 'cure conservatrice et hémodynamique de l'insuffisance veineuse en ambulatoire' (CHIVA)), an approach based on venous hemodynamics with deliberate preservation of the superficial venous system. This is the second update of the review first published in 2013. OBJECTIVES: To compare the efficacy and safety of the CHIVA method with alternative therapeutic techniques to treat varicose veins. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, AMED, and the World Health Organisation International Clinical Trials Registry Platform and ClinicalTrials.gov trials registries to 19 October 2020. We also searched PUBMED to 19 October 2020 and checked the references of relevant articles to identify additional studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared CHIVA to other therapeutic techniques to treat varicose veins. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed and selected studies, extracted data, and performed quantitative analysis from the selected papers. A third author solved any disagreements. We assessed the risk of bias in included trials with the Cochrane risk of bias tool. We calculated the risk ratio (RR), mean difference (MD), number of people needed to treat for an additional beneficial outcome (NNTB), and the number of people needed to treat for an additional harmful outcome (NNTH), with 95% confidence intervals (CI). We evaluated the certainty of the evidence using GRADE. The main outcomes of interest were the recurrence of varicose veins and side effects. MAIN RESULTS: For this update, we identified two new additional studies. In total, we included six RCTs with 1160 participants (62% women) and collected from them eight comparisons. Three RCTs compared CHIVA with vein stripping. One RCT compared CHIVA with compression dressings in people with venous ulcers. The new studies included three comparisons, one compared CHIVA with vein stripping and radiofrequency ablation (RFA), and one compared CHIVA with vein stripping and endovenous laser therapy. We judged the certainty of the evidence for our outcomes as low to very low due to inconsistency, imprecision caused by the low number of events and risk of bias. The overall risk of bias across studies was high because neither participants nor personnel were blinded to the interventions. Two studies attempted to blind outcome assessors, but the characteristics of the surgery limited concealment. Five studies reported the outcome clinical recurrence of varicose veins with a follow-up of 18 months to 10 years. CHIVA may make little or no difference to the recurrence of varicose veins in the lower limb compared to stripping (RR 0.74, 95% CI 0.46 to 1.20; 5 studies, 966 participants; low-certainty evidence). We are uncertain whether CHIVA reduced recurrence compared to compression dressing (RR 0.23, 95% CI 0.06 to 0.96; 1 study, 47 participants; very low-certainty evidence). CHIVA may make little or no difference to clinical recurrence compared to RFA (RR 2.02, 95% CI 0.74 to 5.53; 1 study, 146 participants; low-certainty evidence) and endovenous laser (RR 0.20, 95% CI 0.01 to 4.06; 1 study, 100 participants; low-certainty evidence). We found no clear difference between CHIVA and stripping for the side effects of limb infection (RR 0.83, 95% CI 0.33 to 2.10; 3 studies, 746 participants; low-certainty evidence), and superficial vein thrombosis (RR 1.05, 95% CI 0.51 to 2.17; 4 studies, 846 participants; low-certainty evidence). CHIVA may reduce slightly nerve injury (RR 0.14, 95% CI 0.02 to 0.98; NNTH 9, 95% CI 5 to 100; 4 studies, 846 participants; low-certainty evidence) and hematoma compared to stripping (RR 0.59, 95% CI 0.37 to 0.97; NNTH 11, 95% CI 5 to 100; 2 studies, 245 participants; low-certainty evidence). For bruising, one study found no differences between groups while another study found reduced rates of bruising in the CHIVA group compared to the stripping group. Compared to RFA, CHIVA may make little or no difference to rates of limb infection, superficial vein thrombosis, nerve injury or hematoma, but may cause more bruising (RR 1.15, 95% CI 1.04 to 1.28; NNTH 8, CI 95% 5 to 25; 1 study, 144 participants; low-certainty evidence). Compared to endovenous laser, CHIVA may make little or no difference to rates of limb infection, superficial vein thrombosis, nerve injury or hematoma. The study comparing CHIVA versus compression did not report side effects. AUTHORS' CONCLUSIONS: There may be little or no difference in the recurrence of varicose veins when comparing CHIVA to stripping (low-certainty evidence), but CHIVA may slightly reduce nerve injury and hematoma in the lower limb (low-certainty evidence). Very limited evidence means we are uncertain of any differences in recurrence when comparing CHIVA with compression (very low-certainty evidence). CHIVA may make little or no difference to recurrence compared to RFA (low-certainty evidence), but may result in more bruising (low-certainty evidence). CHIVA may make little or no difference to recurrence and side effects compared to endovenous laser therapy (low-certainty evidence). However, we based these conclusions on a small number of trials with a high risk of bias as the effects of surgery could not be concealed, and the results were imprecise due to the low number of events. New RCTs are needed to confirm these results and to compare CHIVA with approaches other than open surgery.

Chimeric VLPs Bearing VP60 from Two Serotypes of Rabbit Haemorrhagic Disease Virus Are Protective against Both Viruses.

The VP60 capsid protein from rabbit haemorrhagic disease virus (RHDV), the causative agent of one of the most economically important disease in rabbits worldwide, forms virus-like particles (VLPs) when expressed using heterologous protein expression systems such as recombinant baculovirus, yeasts, plants or mammalian cell cultures. To prevent RHDV dissemination, it would be beneficial to develop a bivalent vaccine including both RHDV GI.1- and RHDV GI.2-derived VLPs to achieve robust immunisation against both serotypes. In the present work, we developed a strategy of production of a dual-serving RHDV vaccine co-expressing the VP60 proteins from the two RHDV predominant serotypes using CrisBio technology, which uses Tricholusia ni insect pupae as natural bioreactors, which are programmed by recombinant baculovirus vectors. Co-infecting the insect pupae with two baculovirus vectors expressing the RHDV GI.1- and RHDV GI.2-derived VP60 proteins, we obtained chimeric VLPs incorporating both proteins as determined by using serotype-specific monoclonal antibodies. The resulting VLPs showed the typical size and shape of this calicivirus as determined by electron microscopy. Rabbits immunised with the chimeric VLPs were fully protected against a lethal challenge infection with the two RHDV serotypes. This study demonstrates that it is possible to generate a dual cost-effective vaccine against this virus using a single production and purification process, greatly simplifying vaccine manufacturing.

Randomized Phase III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small-Cell Lung Cancer (PREMER): A GICOR-GOECP-SEOR Study.

PURPOSE: Radiation dose received by the neural stem cells of the hippocampus during whole-brain radiotherapy has been associated with neurocognitive decline. The key concern using hippocampal avoidance-prophylactic cranial irradiation (HA-PCI) in patients with small-cell lung cancer (SCLC) is the incidence of brain metastasis within the hippocampal avoidance zone. METHODS: This phase III trial enrolled 150 patients with SCLC (71.3% with limited disease) to standard prophylactic cranial irradiation (PCI; 25 Gy in 10 fractions) or HA-PCI. The primary objective was the delayed free recall (DFR) on the Free and Cued Selective Reminding Test (FCSRT) at 3 months; a decrease of 3 points or greater from baseline was considered a decline. Secondary end points included other FCSRT scores, quality of life (QoL), evaluation of the incidence and location of brain metastases, and overall survival (OS). Data were recorded at baseline, and 3, 6, 12, and 24 months after PCI. RESULTS: Participants' baseline characteristics were well balanced between the two groups. The median follow-up time for living patients was 40.4 months. Decline on DFR from baseline to 3 months was lower in the HA-PCI arm (5.8%) compared with the PCI arm (23.5%; odds ratio, 5; 95% CI, 1.57 to 15.86; P = .003). Analysis of all FCSRT scores showed a decline on the total recall (TR; 8.7% v 20.6%) at 3 months; DFR (11.1% v 33.3%), TR (20.3% v 38.9%), and total free recall (14.8% v 31.5%) at 6 months, and TR (14.2% v 47.6%) at 24 months. The incidence of brain metastases, OS, and QoL were not significantly different. CONCLUSION: Sparing the hippocampus during PCI better preserves cognitive function in patients with SCLC. No differences were observed with regard to brain failure, OS, and QoL compared with standard PCI.

Long-Term Reliability of the Two-Segment Fusion Technique in the Treatment of Thoracolumbar Fractures Using Screws in the Fractured Vertebra.

BACKGROUND: There is some controversy about which is the best approach, decompression technique and number of fixed levels in the surgical treatment for burst thoracolumbar fractures. Without a neurological injury, correcting thoracolumbar kyphosis and preventing mechanical failure should be the main concerns. The two-segment short fusion with screws at fractured vertebra by posterior approach was performed in 64 patients. Although a significant increase of postoperative kyphosis was observed, there were not clinical consequences, nor was there reintervention for mechanical failure. METHODS: Patients with unstable T11-L2 burst fractures and a two-level fusion including screws at the injured vertebra between 2000 and 2015 were included in the study. Demographic, clinical, and radiological variables were analyzed. Thoracolumbar, segmental, and vertebral kyphosis and anterior and posterior vertebral height were measured preoperatively, postoperatively, at one-year, and at the end of follow-up in the radiological study. The statistical analysis consisted of a descriptive analysis, and we used the t test to compare the preoperative, postoperative, one-year, and end-of-follow-up radiographs to observe a thoracolumbar T10-L2 kyphosis increase. Significance level was established at P < .05. RESULTS: Fifty-four patients were included. A statistically significant increase of vertebral, segmental, and thoracolumbar kyphosis (P < .05) was observed during follow-up, without clinical consequences. CONCLUSIONS: Two-segment fusion is an effective technique and allows initial deformity kyphotic correction after thoracolumbar burst fracture. The thoracolumbar kyphosis increased during the follow-up, without pain, disability, or mechanical failure. LEVEL OF EVIDENCE: 2a.