Case Report: Everolimus reduced bone turnover markers but showed no clinical benefit in a patient with severe progressive osseous heteroplasia.

Background: Progressive osseous heteroplasia (POH) is an ultrarare genetic disorder characterized by an inactivating mutation in the GNAS gene that causes heterotopic ossification. Inhibition of the mammalian target of the rapamycin (mTOR) signalling pathway has been proposed as a therapy for progressive bone fibrodysplasia and non-genetic forms of bone heteroplasia. Herein, we describe the impact of using Everolimus as a rescue therapy for an identical twin girl exhibiting an aggressive clinical phenotype of POH. Methods: Clinical evaluation of the progression of the disease during Everolimus treatment was performed periodically. Cytokine markers involved in bone metabolism and protein markers related to bone activity were analyzed to explore bone turnover activity. Results: The patient received Everolimus therapy for 36 weeks. During treatment, no clinical improvement of the disease was perceived. Analysis of biochemical parameters, namely, ß-CTX (r 2 = -0.576, P-value = 0.016) and PNIP (r 2 = -0.598, P-value = 0.011), indicated that bone turnover activity was significantly reduced. Additionally, bone metabolism-related biomarkers showed only a significant positive correlation with PTH levels. Conclusions: Everolimus treatment did not modify the clinical progression of the disease in an aggressive form of POH, although an impact on the protein markers studied was observed.

Sex-biased expression of the TLR7 gene in severe COVID-19 patients: Insights from transcriptomics and epigenomics.

There is abundant epidemiological data indicating that the incidence of severe cases of coronavirus disease (COVID-19) is significantly higher in males than females worldwide. Moreover, genetic variation at the X-chromosome linked TLR7 gene has been associated with COVID-19 severity. It has been suggested that the sex-biased incidence of COVID-19 might be related to the fact that TLR7 escapes X-chromosome inactivation during early embryogenesis in females, thus encoding a doble dose of its gene product compared to males. We analyzed TLR7 expression in two acute phase cohorts of COVID-19 patients that used two different technological platforms, one of them in a multi-tissue context including saliva, nasal, and blood samples, and a third cohort that included different post-infection timepoints of long-COVID-19 patients. We additionally explored methylation patterns of TLR7 using epigenomic data from an independent cohort of COVID-19 patients stratified by severity and sex. In line with genome-wide association studies, we provide supportive evidence indicating that TLR7 has altered CpG methylation patterns and it is consistently downregulated in males compared to females in the most severe cases of COVID-19.

[Expert opinion on strategies to improve vaccination coverage against seasonal influenza]. / Documento de opinión de expertos para la mejora de la cobertura vacunal frente a la gripe estacional.

Seasonal flu continues to be a major public health concern, and the influenza vaccine remains the most effective preventive measure. In Spain, vaccination coverage data from previous seasons show vaccination rates well below official targets; however, these figures improved significantly after the COVID-19 pandemic. Given the importance of achieving and maintaining high vaccination rates in order to avoid the clinical and economic impact of influenza, our multidisciplinary group of experts on vaccines analyzed the impact of low vaccination rates in Spain and drafted a series of measures to boost influenza vaccination coverage, particularly among priority groups.

[Vaccination against community acquired pneumonia in adults. Update 2021 of the position paper by Neumoexpertos en Prevención Group]. / Vacunación frente a la neumonía adquirida en la comunidad del adulto. Actualización 2021 del posicionamiento del Grupo de Neumoexpertos en Prevención.

Community-acquired pneumonia (CAP) continues to be an important cause of morbidity and mortality in adults. The aim of this study is to update the practical prevention guide for CAP through vaccination in Spain developed in 2016 and updated in 2018, based on available vaccines and evidence through bibliographic review and expert opinion. The arrival of COVID-19 as a new cause of CAP and the recent availability of safe and effective vaccines constitutes the most significant change. Vaccines against pneumococcus, influenza, pertussis and COVID-19 can help to reduce the burden of disease from CAP and its associated complications. The available evidence supports the priority indications established in this guide, and it would be advisable to try to achieve a widespread dissemination and implementation of these recommendations in routine clinical practice.

Rotavirus and autoimmunity.

Rotavirus, a major etiological agent of acute diarrhea in children worldwide, has historically been linked to autoimmunity. In the last few years, several physiopathological approaches have been proposed to explain the leading mechanism triggering autoimmunity, from the old concept of molecular mimicry to the emerging theory of bystander activation and break of tolerance. Epidemiological and immunological data indicate a strong link between rotavirus infection and two of the autoimmune pathologies with the highest incidence: celiac disease and diabetes. The role for current oral rotavirus vaccines is now being elucidated, with a so far positive protective association demonstrated.

Routine infant vaccination of pneumococcal conjugate vaccines has decreased pneumonia across all age groups in Northern Spain.

Since the early 2000s, pneumococcal conjugate vaccines (PCVs) have been shown to be effective in the prevention of pneumonia and invasive pneumococcal diseases. In 2011, the Galician region incorporated PCV in the routine infant immunization, the very first stable program in Spain. We aim to assess direct and indirect benefits of PCV vaccination on all-cause pneumonia in the region across different age groups using an ecological study design. For this, we calculated the annual hospitalization rates using a hospital-based disease registry. We identified all-cause pneumonia, pneumococcal pneumonia and pneumococcal invasive diseases within the registry. Hospitalization rates were computed and compared across three study periods: pre-vaccination (1998-2003), early-vaccination (2005-2009) and routine-vaccination (2011-2015). Across Northern Spain, we identified 114,873 all-cause pneumonia hospitalizations, of which 24,808 were further diagnosed with pneumococcal pneumonia. The majority were elderly > 64 years (67.3%). Hospitalizations from all-cause pneumonia had a net increase from 20.6 (pre-PCV) and 21.4/10,000 (early) to 28.4/10,000 (routine) (+32.7%, p < .0001), this is attributed to the huge number of cases in the elderly age group. In contrast, a net reduction of incidence of hospitalized pneumococcal pneumonia was observed from 6.3/10,000 (pre-PCV) and 5.7/10,000 (early) to 2.4/10,000 (routine) cases (-57.9%, p < .0001). Thus, routine infant vaccination may have resulted to an overall decline of pneumococcal pneumonia in infants, as well as in elderly age groups. However, a paradoxical increase on all-cause pneumonia was observed in Galicia, mostly attributed to the growing number of cases in the elderly population.

Differences between diabetic and non-diabetic patients with community-acquired pneumonia in primary care in Spain.

BACKGROUND: Diabetes is one of the underlying risk factors for developing community-acquired pneumonia (CAP). The high prevalence of diabetes among population and the rising incidence of this illness, converts it as an important disease to better control and manage, to prevent its secondary consequences as CAP. The objective of this research is to describe the characteristics of the patients with diabetes and the differences with the no diabetes who have had an episode of CAP in the context of the primary care field. METHODS: A retrospective, observational study in adult patients (> 18 years-old) who suffer from CAP and attended at primary care in Spain between 2009 and 2013 was developed using the Computerized Database for Pharmacoepidemiological Studies in Primary Care (BIFAP). We carried out a descriptive analysis of the first episodes of CAP, in patients with or without diabetes as comorbidity. Other morbidity (CVA, Anaemia, Arthritis, Asthma, Heart disease, Dementia, Depression, Dysphagia, Multiple sclerosis, Epilepsy, COPD, Liver disease, Arthrosis, Parkinson's disease, Kidney disease, HIV) and life-style factors were also included in the study. RESULTS: A total of 51,185 patients were included in the study as they suffer from the first episode of CAP. Of these, 8012 had diabetes as comorbidity. There were differences between sex and age in patients with diabetes. Patients without diabetes were younger, and had less comorbidities including those related to lifestyles such as smoking, alcoholism, social and dental problems than patients with diabetes. CONCLUSIONS: Patients who developed an episode of CAP with diabetes have more risk factors which could be reduced with an appropriate intervention, including vaccination to prevent successive CAP episodes and hospitalization. The burden of associated factors in these patients can produce an accumulation of risk. Health care professional should know this for treating and control these patients in order to avoid complications. Diabetes and those other risk factors associated could be reduced with an appropriate intervention, including vaccination to prevent the first and successive CAP episodes and the subsequent hospitalization in severe cases.

Impact of rotavirus vaccination on childhood hospitalizations for seizures: Heterologous or unforeseen direct vaccine effects?

There is a growing interest in the possible relationship between rotavirus (RV) vaccine and hospitalizations due to childhood seizures. We explored variation in hospitalization rates after 9 years of vaccination against pre-vaccination period for children <5 years of age from Galicia (Northwest Spain) before and after the introduction of the RV vaccines. Hospitalization rates for childhood seizures in Galician children were compared before and after RV vaccine introduction (in 2007) using different statistical approaches, including time series analyses. Our study cohort totaled 7,712 children <5 years of age admitted to hospital between 2002 and 2015 for "all kind of childhood seizures". Hospitalization rates decreases steadily with reductions ranging from 22.3% (95% CI: 15.0-29.1) in 2008, to 50.9% (95% CI: 45.5-55.7) in 2014, and significant results were also observed for <1, 1, and 2-year-old children in comparison with pre-vaccination period hospitalization rate. Regression models indicate a negative association between RV vaccination and hospitalizations for all kind of seizures. In addition, time series analyses are consistent with this finding and predict that vaccination coverage will affect hospitalization rates for "all kind of seizures" after 9 months. The results strongly support that RV vaccination has significantly reduced hospitalization rates due to childhood seizures.

Vacunación frente a la neumonía adquirida en la comunidad del adulto. Actualización 2018 del posicionamiento del Grupo de Neumoexpertos en Prevención / Adult community acquired pneumonia vaccination: 2018 Update of the positioning of the Pneumonia Prevention Expert Group

La neumonía adquirida en la comunidad (NAC) continúa siendo una causa importante de morbimortalidad en adultos. El objetivo de este documento es actualizar la guía práctica de prevención de la NAC mediante vacunación en España desarrollada en 2016 en función de las vacunas y evidencias disponibles mediante revisión bibliográfica y opinión de expertos. Las vacunas frente al neumococo y la gripe continúan siendo las principales herramientas preventivas disponibles frente a la NAC, y pueden contribuir a disminuir la carga de enfermedad por NAC y sus complicaciones asociadas. La evidencia disponible avala las indicaciones prioritarias establecidas en esta guía, y sería recomendable tratar de lograr una difusión e implementación amplia en la práctica clínica rutinaria de estas recomendaciones

Community-acquired pneumonia (CAP) continues to be an important cause of morbidity and mortality in adults. The aim of this study is to update the 2016 practical prevention guidelines for CAP through vaccination in Spain, based on the available vaccines, as well as the evidence using a literature review and expert opinion. Vaccines against pneumococcus and influenza continue to be the main prevention tools available against CAP, and can contribute to reduce the burden of disease due to CAP and its associated complications. The available evidence supports the priority indications established in these guidelines, and it would be advisable to try to achieve a widespread dissemination and implementation of these recommendations in routine clinical practice

[Adult community acquired pneumonia vaccination: 2018 Update of the positioning of the Pneumonia Prevention Expert Group]. / Vacunación frente a la neumonía adquirida en la comunidad del adulto. Actualización 2018 del posicionamiento del Grupo de Neumoexpertos en Prevención.

Community-acquired pneumonia (CAP) continues to be an important cause of morbidity and mortality in adults. The aim of this study is to update the 2016 practical prevention guidelines for CAP through vaccination in Spain, based on the available vaccines, as well as the evidence using a literature review and expert opinion. Vaccines against pneumococcus and influenza continue to be the main prevention tools available against CAP, and can contribute to reduce the burden of disease due to CAP and its associated complications. The available evidence supports the priority indications established in these guidelines, and it would be advisable to try to achieve a widespread dissemination and implementation of these recommendations in routine clinical practice.

Salivary epidermal growth factor correlates with hospitalization length in rotavirus infection.

BACKGROUND: The IFI27 interferon gene expression has been found to be largely increased in rotavirus (RV)-infected patients. IFI27 gene encodes for a protein of unknown function, very recently linked to epidermal proliferation and related to the epidermal growth factor (EGF) protein. The EGF is a low-molecular-weight polypeptide that is mainly produced by submandibular and parotid glands, and it plays an important physiological role in the maintenance of oro-esophageal and gastric tissue integrity. Our aim was to determine salivary EGF levels in RV-infected patients in order to establish its potential relationship with IFI27 increased expression and EGF-mediated mucosal protection in RV infection. METHODS: We conducted a prospective comparative study using saliva samples from 27 infants infected with RV (sampled at recruitment during hospital admission and at convalescence, i.e. at least 3 months after recovery) and from 36 healthy control children. RESULTS: Median (SD) EGF salivary concentration was 777 (529) pg/ml in RV-infected group at acute phase and 356 (242) pg/m at convalescence, while it was 337 (119) pg/ml in the healthy control group. A significant association was found between EGF levels and hospitalization length of stay (P-value = 0.022; r2 = -0.63). CONCLUSIONS: The salivary levels of EGF are significantly increased during the acute phase of natural RV infection, and relate to length of hospitalization. Further assessment of this non-invasive biomarker in RV disease is warranted.

Incidence and risk factor prevalence of community-acquired pneumonia in adults in primary care in Spain (NEUMO-ES-RISK project).

BACKGROUND: Community-acquired pneumonia (CAP) is a major cause of morbidity and mortality in adults even in developed countries. Several lifestyle factors and comorbidities have been linked to an increased risk, although their prevalence has not been well documented in the primary care setting. The aim of this study is to assess the incidence, risk factor and comorbid conditions distribution of CAP in adults in primary care in Spain. METHODS: Retrospective observational study in adults (>18 years-old) with CAP diagnosed and attended at primary care in Spain between 2009 and 2013, using the Computerized Database for Pharmacoepidemiological Studies in Primary Care (BIFAP). RESULTS: Twenty-eight thousand four hundred thirteen patient records were retrieved and analyzed. Mean age (standard deviation): 60.5 (20.3) years, 51.7 % males. Global incidence of CAP in adults was estimated at 4.63 per 1000 persons/year. CAP incidence increased progressively with age, ranging from a 1.98 at 18-20 years of age to 23.74 in patients over 90 years of age. According to sex, global CAP incidence was slightly higher in males (5.04) than females (4.26); CAP incidence from 18 to 65 year-olds up was comparable between males (range: 2.18-5.75) and females (range: 1.47-5.21), whereas from 65 years of age, CAP incidence was noticeable higher in males (range: 7.06-36.93) than in females (range: 5.43-19.62). Average prevalence of risk factors was 71.3 %, which increased with age, doubling the risk in males by the age of 75 (females 20 % vs males 40 %). From 55 years of age, at least one risk factor was identified in 85.7 % of cases: one risk factor (23.8 %), two risk factors (23.4 %), three or more risk factors (38.5 %). Major risk factors were: metabolic disease (27.4 %), cardiovascular disease (17.8 %) and diabetes (15.5 %). CONCLUSIONS: The annual incidence of CAP in primary care adults in Spain is high, comparable between males and females up to 65 years of age, but clearly increasing in males from that age. CAP risk increases with age and doubles in males older than 75 years. The majority of CAP cases in patients over 55 years of age is associated to at least one risk factor. The main risk factors associated were metabolic disease, cardiovascular disease, and diabetes.

Faringoamigdalitis no estreptocócicas ¿hay "algo" más allá de las guías clínicas? / No disponible

No disponible

Una causa inusual de hematomas / An unusual cause of bruising

No disponible

El hipotiroidismo primario autoinmune: causa de tos crónica en pediatría / Primary autoimmune hypothyroidism, a cause of chronic cough in pediatrics

La tos crónica (la que persiste más de 4 semanas) es un motivo de consulta frecuente en atención primaria. La evaluación de un niño con tos crónica debe incluir una historia clínica detallada, una radiografía de tórax y una espirometría en el niño colaborador; además se suele recomendar un estudio de alergia en los niños mayores de 3-4 años. Presentamos el caso de una niña de 10 años de edad con tos crónica, y describimos el proceso diagnóstico desarrollado, así como la presencia de bocio hipotiroideo autoinmune, que relacionamos con sus síntomas y la evolución posterior. El bocio puede ser causa de tos crónica. En los pacientes con tos crónica, además de realizar una historia general y dirigida, las exploraciones complementarias según los datos obtenidos y un seguimiento clínico, se recomienda valorar la vía respiratoria superior y el cuello(AU)

Chronic cough (a cough lasting longer than 4 weeks) is a common symptom presented to primary care. The evaluation of a child with chronic cough should include a detailed medical history, physical examination, chest radiograph, spirometry (if the child is able), and allergy evaluation-skin test- is often recommended (elder than 3-4 years old). We describe evaluation, diagnosis, treatment, and evolution in a 10 years old girl with chronic cough and the relationship between goiter, autoimmune hypothyroidism and her symptoms. A goiter can cause chronic cough. In patients with chronic cough, besides detailed medical history, physical examination, further investigation in accordance with the previous results and follow-up, it is recommended not to forget to evaluate the upper airway and neck(AU)

Displasia evolutiva de cadera: controversia sobre el cribado ecográfico universal / Developmental hip dysplasia: controversy on universal echographic screening

Pese a la elevada incidencia de displasia de cadera clínicamente importante (3-5 casos por cada 1000 recién nacidos vivos) y a los ampliamente estudiados factores de riesgo principales (parto de presentación podálica, sexo femenino y antecedentes familiares de displasia evolutiva de cadera), no se ha conseguido encontrar una estrategia efectiva que reduzca la incidencia de casos tardíos. Reabrimos, a propósito de un caso, la controversia existente acerca del cribado ecográfico universal en la patología osteomuscular más frecuente de la infancia (AU)

Despite the elevated incidence of clinically relevant hip dysplasia (3-5 per 1000 live births) and the broadly studied main risk factors (breech position, female sex and family cases), we have not achieved an effective prevention strategy, and so the detection of late cases has not decreased. We reopen, following a case, the existent controversy upon universal ultrasound screening on the most frequent musculo-skeletal disorder in the infancy (AU)