[Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention]. / Comentario del CEIPV a las nuevas Guías Europeas de Prevención Cardiovascular 2021.

Statement of the Spanish Interdisciplinary Vascular Prevention Committee on the updated European Guidelines on Cardiovascular Disease Prevention. We present the Spanish adaptation of the 2021 European Guidelines on Cardiovascular Disease (CVD) prevention in clinical practice. The current guidelines besides the individual approach greatly emphasize on the importance of population level approaches to the prevention of cardiovascular diseases. Systematic global CVD risk assessment is recommended in individuals with any major vascular risk factor. Regarding LDL-Cholesterol, blood pressure, and glycemic control in patients with diabetes mellitus, goals and targets remain as recommended in previous guidelines. However, it is proposed a new, stepwise approach (Step 1 and 2) to treatment intensification as a tool to help physicians and patients pursue these targets in a way that fits patient profile. After Step 1, considering proceeding to the intensified goals of Step 2 is mandatory, and this intensification will be based on 10-year CVD risk, lifetime CVD risk and treatment benefit, comorbidities and patient preferences. The updated SCORE algorithm-SCORE2, SCORE-OP- is recommended in these guidelines, which estimates an individual's 10-year risk of fatal and non-fatal CVD events (myocardial infarction, stroke) in healthy men and women aged 40-89 years. Another new and important recommendation is the use of different categories of risk according different age groups (< 50, 50-69 ≥ 70 years). Different flow charts of CVD risk and risk factor treatment in apparently healthy persons, in patients with established atherosclerotic CVD, and in diabetic patients are recommended. Patients with chronic kidney disease are considered high risk or very high-risk patients according to the levels of glomerular filtration rate and albumin-to-creatinine ratio. New lifestyle recommendations adapted to the ones published by the Spanish Ministry of Health as well as recommendations focused on the management of lipids, blood pressure, diabetes and chronic renal failure are included.

A WIDESPREAD NOVEL GAMMAHERPESVIRUS IN APPARENTLY HEALTHY WILD QUOKKAS (SETONIX BRACHYURUS): A THREATENED AND ENDEMIC WALLABY OF WESTERN AUSTRALIA.

Five genetically distinct macropodid marsupial herpesviruses have been reported [Macropodid alphaherpesviruses 1 and 2 (MaHV-1 and -2); Macropodid herpesviruses 3 to 5 (MaHV-3 to -5)]. MaHV-2 was originally isolated from an outbreak of fatal disease in captive quokkas (Setonix brachyurus) that were in contact with other macropodid species. This warranted a survey of the presence of herpesviruses in this threatened and endemic Western Australian (WA) wallaby. Blood samples from 142 apparently healthy quokkas were tested for exposure to MaHV-1 and -2 by serology. Of these 142, 121 [Rottnest Island (RI), n = 93; mainland WA, n = 28] were tested for herpesvirus infection by polymerase chain reaction (PCR). Antibodies to MaHV-1 and -2 were detected in one individual [prevalence, 0.7%; 95% confidence interval (CI), 0.1%-3.2%] from the mainland and none from RI. However, a novel gammaherpesvirus [designated Macropodid herpesvirus 6 (MaHV-6)] was detected by PCR in the blood of 13 of 121 individuals (11%; 95% CI, 6.2-17.2). Infection with MaHV-6 was significantly more prevalent on the mainland (7/28; i.e., 25%) compared with RI (6/93; i.e., 6.45%; difference in sample proportions, 95% CI, 6%-32%; P = 0.015). There was no association (P > 0.05) between infection with MaHV-6 and differences in hematology, blood chemistry, peripheral blood cell morphologies, or on clinical status. There was a significant association between infection with MaHV-6 and the presence of Theileria spp. in blood [odds ratio (OR) = 11.0; 95% CI, 2.31-52.3; P = 0.001] and yeast in the nasal lining (OR = 7.0; 95% CI, 1.54-31.8; P = 0.021), suggesting that quokkas may be more susceptible to infection with these microorganisms if also infected with MaHV-6. MaHV-6 infection may be a catalyst for vulnerability to disease with other infectious agents and may pose a significant threat to other macropods. These findings have implications for in situ and ex situ management programs of quokkas.

A meta-analysis on the comparison between pediatric inguinal herniotomies performed with and without incising the external oblique aponeurosis in terms of recurrence and complications

RATIONALE@#There is a diversity of methods in performing pediatric inguinal herniotomy, but no consensus on which is the gold standard. The two most common are the Ferguson technique and the MitchellBanks technique. The objective of this meta-analysis was to compare the two techniques in terms of hernia recurrence and post-operative complications: namely hematoma, hydrocele, testicular ascent, and testicular atrophy.@*METHODS@#Three randomized controlled trials and one multi-center retrospective study were included in this meta-analysis. Using the Cochrane Collaboration tool and Newcastle-Ottawa quality assessment scale, all studies included were deemed to be of good quality and have low risk of bias. Revman 5.3 was used for all statistical analyses.@*RESULTS@#There was no significant difference in terms of hernia recurrence between the two techniques (OR = 0.85, 95% CI = 0.31- 2.36). For post-operative complications, hematoma (OR = 0.64, 95% CI = 0.37-1.13), testicular ascent (OR = 0.28, 95% CI = 0.05- 1.50), and testicular atrophy (OR = 2.02, 95% CI = 0.54-7.52) did not differ between the two techniques. Only the incidence of postoperative hydrocele significantly differed between the two techniques, being higher when the external oblique aponeurosis was opened (OR = 0.44, 95% CI = 0.27-0.70). @*CONCLUSION@# Performing pediatric inguinal herniotomy without opening the external oblique aponeurosis is a safe procedure and may be recommended as an optimal choice of method for uncomplicated cases.

Management of Wilms’ tumor in a horseshoe kidney at the time of COVID-19 pandemic: A case report

@#Wilms’ tumor is one of the most frequent tumors in childhood. The incidence of Wilms’ tumor in a horseshoe kidney is estimated at 0.4 to 0.9%. It is highly treatable but a fast growing tumor. Management of cancer patients has become a dilemma for surgeons, due to the impact of the COVID-19 pandemic on the health care sector globally. Reported here is a rare case of a 2 year old boy, diagnosed with Wilms’ tumor in a horseshoe kidney. This report aimed to highlight the multimodality treatment of Wilms' tumor and the modifications to cancer diagnostic and treatment protocols to adapt to the current health care crisis brought about by the pandemic.

Identification and characterization of high-yielding, short-duration rice genotypes for tropical Asia.

Previous efforts to increase the yield of tropical rice (Oryza sativa L.) have focused on medium-duration varieties. However, there is increasing demand for high-yielding short-duration varieties that can adapt to intensified cropping systems and climate change. Our goal was to identify physiological traits associated with high yield in elite short-duration genotypes suitable for tropical Asia. We conducted field experiments in five consecutive growing seasons at the International Rice Research Institute, the Philippines. We selected genotypes in the first two seasons, then performed a detailed characterization of the most promising genotypes in the following three seasons. Of the 50 advanced-generation genotypes, three had consistently high yield and early maturity, with yields 11 to 38% higher than that of 'IRRI104' ('IR50404-57-2-2-3'), a short-duration variety that is widely grown in Southeast Asia. These genotypes were 20 to 32 cm taller than IRRI104. We found that for grain growth, low source capacity, defined as stem nonstructural carbohydrates at heading plus biomass accumulation after heading, was the major factor for the low yield of IRRI104. Although sink capacity (spikelets m-2 × grain weight) in the promising genotypes was comparable to that of IRRI104, they had a 25 to 53% higher source-sink ratio (source capacity/sink capacity) than IRRI104, which was attributed to larger leaf area and greater biomass accumulation during the grain-filling stage. This result suggests that slight changes in plant development to promote height combined with increased leaf area around heading would improve the yield of short-duration rice varieties in tropical Asia.

Mapping B lymphocytes as major reservoirs of naturally occurring latent equine herpesvirus 5 infection.

Equine herpesvirus 5 (EHV5) is a commonly detected gammaherpesvirus, which, along with the closely related EHV2, constitute the only two known percaviruses that infect horses. Apart from detection in horse populations worldwide and the recent publication of the whole genome, there is little known about the biology and pathogenesis of this virus, with many assumptions made by parallels with EHV2. The long-term survival of gammaherpesviruses within infected hosts involves the establishment and maintenance of latency in selected cell and tissues types, particularly lymphocytes. A latent gammaherpesvirus infection is characterized by a limited number of genes expressing in a particular cell or tissue type. In this study, we have used in vitro co-culturing to detect EHV5 in equine PBMCs and characterize the predominant cellular site for the establishment and maintenance of a latent infection. These experiments were conducted by isolating PBMCs from 10 horses and sorting subpopulations into two T lymphocyte (CD4 and CD8), B lymphocyte and macrophage enriched or depleted fractions. These lymphocyte and macrophage fractions were examined for the presence of latent EHV5 by in vitro co-culturing with equine foetal kidney cells. The lymphocyte fraction enriched with B lymphocytes had a significantly increased (P=0.005) number of plaques formed during co-culturing, whereas the B lymphocyte depleted fraction had a significant reduction in the number of plaques formed after co-culturing. Taken together, these results demonstrate that equine gammaherpesviruses establish latency in the equine PBMCs, with the predominant site for maintenance of latent virus being B lymphocytes.

Detection and identification of a gammaherpesvirus in Antechinus spp. in Australia.

We detected herpesvirus infection in a male yellow-footed antechinus (Antechinus flavipes) and male agile antechinus (Antechinus agilis) during the period of postmating male antechinus immunosuppression and mortality. Histopathologic examination of tissues revealed lesions consistent with herpesvirus infection in the prostate of both animals. Herpesvirus virions were observed by transmission electron microscopy in the prostate tissue collected from the male yellow-footed antechinus. Herpesvirus DNA was detected in prostate, liver, lung, kidney, spleen, and ocular/nasal tissues using a pan-herpesvirus PCR targeting the viral DNA polymerase. Nucleotide sequencing identified a novel herpesvirus from the Gammaherpesvirinae subfamily that we have tentatively designated dasyurid herpesvirus 1 (DaHV-1).

Comparing the genetic diversity of ORF30 of Australian isolates of 3 equid alphaherpesviruses.

A single nucleotide polymorphism (SNP) has been previously associated with EHV-1 neurological disease in several countries around the world. This disease is very uncommon in Australia and little information is available about the presence of this SNP in Australian EHV-1 isolates. The ORF30 sequence of 66 Australian EHV-1 isolates was determined and the genotype was compared to the disease manifestation of the case from which the virus was isolated. Of the 66 isolates, 61 were from cases of abortion and 5 were cases associated with equine herpesvirus myeloencephalopathy (EHM). There was no association between pathotype and genotype in these isolates. In total, 64 of the 66 isolates encoded N752, including 4 isolates from EHM cases. The ORF30 sequence was also determined for 14 EHV-4 isolates, including 2 isolates from confirmed EHV-4 abortion cases. All 14 EHV-4 isolates had aspartic acid at the position equivalent to EHV-1 AA752. Aspartic acid was also confirmed in this position for the single isolate of AHV-3 sequenced in this study. The nucleotide sequence of ORF68 was also determined and showed considerable genetic heterogeneity in the EHV-1 isolates, however, this ORF was highly conserved among the 14 EHV-4 isolates sequenced, with only one SNP identified among 7 isolates. These results confirm that the EHV1 ORF30 N752 is unique and that the D752 sequence is most likely to be the true parent strain of this virus. We suggest that the abortigenic form of EHV-1 should be considered to be the more recently emerged mutant.

Phylogenetic and molecular epidemiological studies reveal evidence of multiple past recombination events between infectious laryngotracheitis viruses.

In contrast to the RNA viruses, the genome of large DNA viruses such as herpesviruses have been considered to be relatively stable. Intra-specific recombination has been proposed as an important, but underestimated, driving force in herpesvirus evolution. Recently, two distinct field strains of infectious laryngotracheitis virus (ILTV) have been shown to have arisen from independent recombination events between different commercial ILTV vaccines. In this study we sequenced the genomes of additional ILTV strains and also utilized other recently updated complete genome sequences of ILTV to confirm the existence of a number of ILTV recombinants in nature. Multiple recombination events were detected in the unique long and repeat regions of the genome, but not in the unique short region. Most recombinants contained a pair of crossover points between two distinct lineages of ILTV, corresponding to the European origin and the Australian origin vaccine strains of ILTV. These results suggest that there are two distinct genotypic lineages of ILTV and that these commonly recombine in the field.

Comparative analysis of the complete genome sequences of two Australian origin live attenuated vaccines of infectious laryngotracheitis virus.

Infectious laryngotracheitis virus (ILTV) is an alphaherpesvirus that causes acute respiratory disease in poultry. Live attenuated ILTV vaccines have been used extensively to help control outbreaks of disease. Two Australian-origin attenuated vaccine strains, SA2 and A20 ILTV, are commercially available and are in frequent use in Australia. Both these vaccines are of chicken embryo origin (CEO). The A20 ILTV strain was developed from the SA2 ILTV strain by sequential passage of SA2 ILTV in tissue culture in order to reduce its residual virulence. Previous studies in our laboratories have demonstrated the greater attenuation of A20 ILTV under controlled experimental conditions, but the genetic basis of the in vivo phenotypes of A20 and SA2 ILTV has not been elucidated. In this study, the genetic differences between A20 and SA2 ILTV were examined by performing complete genome sequencing and comparative analysis. The genome sequences were also compared to a reference sequence from another CEO ILTV vaccine (Serva ILTV: GenBank accession number HQ_630064) of European-origin. Additional in ovo studies to assess cell to cell spread were performed in order to allow further comparisons of the pathogenicity of SA2 and A20 ILTV. The sequencing results showed that the genome sizes of SA2 and A20 ILTV were 152,975 and 152,978bp, respectively, while Serva ILTV had a genome size of 152,630bp. The genomes of SA2 and A20 ILTV shared 99.9% nucleotide sequence identity with each other, but only 99.2% identity with Serva ILTV. In complete genome alignments between SA2 and A20 ILTV, a total of 24 single nucleotide polymorphisms (SNPs) were identified, but only two of these were non-synonymous. These were located in the ORF B and UL15 genes. Four indels were detected in non-coding regions. The findings from this study demonstrate the general genetic stability of ILTV, but also show that non-synonymous changes in the ORF B and UL15 genes have arisen following tissue culture passage of SA2 ILTV to produce the A20 vaccine. It is likely that these non-synonymous changes are related to the greater attenuation of A20 ILTV compared to SA2 ILTV, and to the reduced ability of A20 ILTV to spread from cell to cell, as observed in this study. The results from this study also demonstrate the divergence between the genomes of the Australian-origin ILTV vaccine strains and the Serva vaccine strain.

First complete genome sequence of infectious laryngotracheitis virus.

BACKGROUND: Infectious laryngotracheitis virus (ILTV) is an alphaherpesvirus that causes acute respiratory disease in chickens worldwide. To date, only one complete genomic sequence of ILTV has been reported. This sequence was generated by concatenating partial sequences from six different ILTV strains. Thus, the full genomic sequence of a single (individual) strain of ILTV has not been determined previously. This study aimed to use high throughput sequencing technology to determine the complete genomic sequence of a live attenuated vaccine strain of ILTV. RESULTS: The complete genomic sequence of the Serva vaccine strain of ILTV was determined, annotated and compared to the concatenated ILTV reference sequence. The genome size of the Serva strain was 152,628 bp, with a G + C content of 48%. A total of 80 predicted open reading frames were identified. The Serva strain had 96.5% DNA sequence identity with the concatenated ILTV sequence. Notably, the concatenated ILTV sequence was found to lack four large regions of sequence, including 528 bp and 594 bp of sequence in the UL29 and UL36 genes, respectively, and two copies of a 1,563 bp sequence in the repeat regions. Considerable differences in the size of the predicted translation products of 4 other genes (UL54, UL30, UL37 and UL38) were also identified. More than 530 single-nucleotide polymorphisms (SNPs) were identified. Most SNPs were located within three genomic regions, corresponding to sequence from the SA-2 ILTV vaccine strain in the concatenated ILTV sequence. CONCLUSIONS: This is the first complete genomic sequence of an individual ILTV strain. This sequence will facilitate future comparative genomic studies of ILTV by providing an appropriate reference sequence for the sequence analysis of other ILTV strains.

Virion associated proteins of equine rhinitis B virus 1 (ERBV1): the non-structural protein 3C(pro) co-purifies with virions.

Equine rhinitis B virus (ERBV), genus Erbovirus, is most closely related to the Cardiovirus genus in the family Picornaviridae. The structural proteins (VP1-4) of erboviruses are not well described, but are predicted by sequence to be 35, 29, 26 and 7 kDa. Methods for the purification of cardioviruses (polyethylene glycol, trypsin treatment) were used to characterise the structural proteins of ERBV1. Only one of the virus proteins detected was an expected molecular mass, and this 26 kDa protein was identified as VP3 by N-terminal amino acid sequencing. N-terminal sequencing of the 56 and a 29 kDa protein identified sequences consistent with VP2 and VP1 respectively, despite these being 27 kDa larger and 6 kDa smaller than predicted. Virus purified without trypsin showed proteins more consistent with masses predicted for VP1, VP2 and VP3 at 35, 29 and 26 kDa respectively. These proteins were further identified with antibodies affinity purified to recombinant VP1, VP2, VP3 produced in E. coli. Interestingly, antibodies affinity purified to the non-structural protein 3C(pro), produced in insect cells, strongly detected a 27 kDa protein in western blots of virus purified with and without trypsin treatment, suggesting the non-structural 27 kDa 3C(pro) co-purifies with ERBV1 virions.

Comparative effectiveness of azathioprine in Crohn's disease and ulcerative colitis: prospective, long-term, follow-up study of 394 patients.

BACKGROUND: The long-term efficiacy for thiopurinic drugs in Crohn's disease (CD), and particularly in ulcerative colitis (UC), has been insufficiently studied. AIM: To evaluate prospectively and compare the long-term effectiveness of azathioprine (AZA) in CD and UC. METHODS: Three hundred and ninety-four AZA treated patients were included consecutively included. Truelove-modified index and CDAI were used to assess effectiveness. Hospitalizations and surgical procedures were recorded. RESULTS: Two hundred and thirty-eight patients with CD and 156 with UC received AZA for a median of 38 months. EFFECTIVENESS: Partial response/remission was achieved in 34%/49% of CD patients and in 47%/42% of UC (nonstatistically significant differences). STEROID TREATMENT: Prior to AZA, 49% of CD patients were receiving steroids, whereas only 8% needed steroids after therapy (P < 0.001). Corresponding figures in UC patients were 39% vs. 9% (P < 0.001). HOSPITALIZATIONS: Prior to AZA, the rate of hospitalizations in CD was 0.190 per-patient-year, while after treatment, it decreased to 0.099 (P < 0.001). Corresponding hospitalization rates in UC were 0.108 vs. 0.038 (P < 0.001). SURGERY: The rate of surgery in CD prior/after AZA was 0.038/0.011 per-patient-year (P < 0.001). The number of surgical interventions in UC prior/after AZA treatment was 26/0 (the rate per-patient-year was 0.018/0) (P < 0.001). CONCLUSIONS: Our results confirm the effectiveness of AZA in inflammatory bowel disease, not only in the short term but also in the long term, resulting in a steroid sparing effect and in both a reduction in the number of hospitalizations and surgical procedures. AZA is similarly effective for both CD and UC patients.

[CARD15 mutations are poorly related to Crohn's disease phenotypes in Asturias]. / Las mutaciones del gen CARD15 presentan escasa relación con los fenotipos de la enfermedad de Crohn en Asturias.

BACKGROUND: the association between the three common CARD15 gene mutations (R702W, G908R, L1007fs) and the genetic susceptibility to Crohn s disease (CD) have been confirmed by several studies, with some differences found, in relation to geographic areas and ethnic groups. OBJECTIVES: To analyze the prevalence of CARD15 gen and its polymorphisms in patients with CD in Asturias and its possible correlation with the different genotypes of the disease. METHODS: a total of 216 CD patients recruited from Asturias (North of Spain) and 86 ethnically matched healthy controls, were typed using Hybprobes on a LightCycler instrument for CARD15 mutations. Patients were subdivided according to Vienna classification. We have studied the frequency of these mutations in the different subgroups of CD patients and analyzed its contribution to the disease clinical characteristics and progression. RESULTS: carrier frequencies for CARD15 mutations in our CD patients were similar to controls (17.8 vs. 17.4%) respectively (NS). CD patients exhibited frequencies of 8.8, 3.0 and 6.0% for the R702, G908R and L1007fs polymorphisms respectively, whereas our control population had allele frequencies of 11.6, 2.3 and 3.5% for the three mutations respectively (NS). We did not find any relationship between CARD15 mutations and the different phenotypes of Crohn s disease, according to Vienna classification. CONCLUSIONS: in our CD population, other factors (i.e. environmental), in addition to genetics, must be mainly involved in the development of the disease.

Las mutaciones del gen CARD15 presentan escasa relación con los fenotipos de la enfermedad de Crohn en Asturias / CARD15 mutations are poorly related to Crohn´s disease phenotypes in Asturias

Introducción: la asociación entre las mutaciones del genCARD15 y la susceptibilidad genética para la enfermedad deCrohn (EC) se ha confirmado en diversos estudios, con ampliasvariaciones observadas a nivel mundial, tanto geográficas comoétnicas.Objetivos: analizar la prevalencia de gen CARD 15 y sus polimorfismosen pacientes con EC en Asturias y su posible correlacióncon los diversos fenotipos de la enfermedad.Métodos: estudiamos la frecuencia de las tres mutaciones delgen CARD15 (R702W, G908R, L1007fs) usando cebadores específicos,en un total de 216 pacientes con EC y 86 controlesprocedentes del área de Oviedo. Los pacientes fueron clasificadosde acuerdo con la edad al diagnóstico, localización la enfermedady su comportamiento clínico (clasificación de Viena).Resultados: la frecuencia global de portadores de las mutacionesdel gen CARD15 en los pacientes con EC fue del 17,3%frente a un 17,6% en controles (NS). Al analizar separadamentelos polimorfismos R702, G908R y L1007fs los pacientes mostrabanfrecuencias del 8,8, 3 y 6% respectivamente, mientras quelos controles las presentaban en el 11,6, 2,3 y 3,5%, sin encontrardiferencias significativas para ninguna de ellas (NS). Las frecuenciasobservadas en controles, fueron similares a las encontradasen otras regiones españolas.Conclusiones: la prevalencia de mutaciones en CARD15 enpacientes con EC en Asturias es menor a la reportada en otrostrabajos publicados en población española. Otros factores ambientales,además de los genéticos, parecen tener mayor importanciaen el desarrollo de EC en nuestra área

Background: the association between the three commonCARD15 gene mutations (R702W, G908R, L1007fs) and the geneticsusceptibility to Crohn’s disease (CD) have been confirmedby several studies, with some differences found, in relation to geographicareas and ethnic groups.Objectives: To analyze the prevalence of CARD15 gen andits polymorphisms in patients with CD in Asturias and its possiblecorrelation with the different genotypes of the disease.Methods: a total of 216 CD patients recruited from Asturias(North of Spain) and 86 ethnically matched healthy controls, weretyped using Hybprobes on a LightCycler instrument for CARD15mutations. Patients were subdivided according to Vienna classification.We have studied the frequency of these mutations in thedifferent subgroups of CD patients and analyzed its contributionto the disease clinical characteristics and progression.Results: carrier frequencies for CARD15 mutations in ourCD patients were similar to controls (17.8 vs. 17.4%) respectively(NS). CD patients exhibited frequencies of 8.8, 3.0 and 6.0% forthe R702, G908R and L1007fs polymorphisms respectively,whereas our control population had allele frequencies of 11.6,2.3 and 3.5% for the three mutations respectively (NS).We did not find any relationship between CARD15 mutationsand the different phenotypes of Crohn’s disease, according to Viennaclassification.Conclusions: in our CD population, other factors (i.e. environmental),in addition to genetics, must be mainly involved in thedevelopment of the disease

[Increased prevalence of celiac disease in first and second-grade relatives. A report of a family with 19 studied members]. / Prevalencia aumentada de enfermedad celiaca en familiares de primer y segundo grado: descripción de una familia con 19 miembros estudiados.

INTRODUCTION: celiac disease (CD) is an autoimmune condition that is triggered by the ingestion of gluten, a substance present in most cereals, and that affects genetically predisposed individuals. As a result, this condition is clearly familial, and mainly associated with HLA class II markers. OBJECTIVES: in this work we set out to analyze the prevalence of CD in an extensive family based on an index subject who had already died from this disease a few years ago, where CD had been complicated by the development of a small-bowel malignancy, namely an adenocarcinoma. METHODS: nineteen members were studied. They all were subjected to a diagnostic protocol including a detailed medical history, hemogram, coagulation tests, and blood biochemistry (including liver function tests, serum iron metabolism, circulating folic acid and vitamin B12 levels, thyroid function tests, tissue transglutaminase measurement, and genetic markers (DQ2 and DQ8). Suspect cases underwent gastroscopy plus multiple duodenal biopsy for confirmation. RESULTS: overall we encountered CD in 9/19 studied members, which represents 47.4% with the following distribution according to degree of kinship -four of seven siblings (57%); one of three children (33.3%); three of eight nephews and nieces (37.5%), and the only grandnephew, who was 9 years old. CONCLUSIONS: from all this it may be seen that family studies are needed every time a patient is diagnosed with celiac disease; these studies should include both first- and second-degree relatives, given the high prevalence encountered and the fact that these tests are relatively straighforward to perform.

Prevalencia aumentada de enfermedad celiaca en familiares de primer y segundo grado: descripción de una familia con 19 miembros estudiados / Increased prevalence of celiac disease in first-grade relatives. A report of a family with 19 studied members

Introducción: la enfermedad celiaca (EC) es un proceso autoinmune, desencadenado por la ingesta del gluten contenido en la mayor parte de los cereales, que afecta a individuos genéticamente predispuestos. Por todo ello, muestra una clara tendencia familiar, centrada fundamentalmente en marcadores del sistema HLA de clase II. Objetivos: nos propusimos en el presente trabajo analizar la prevalencia de EC en una familia extensa, a partir de un caso índice fallecido hacía unos años, como consecuencia de padecer la misma enfermedad, complicada además con el desarrollo de un tumor maligno del intestino delgado, del tipo del adenocarcinoma. Métodos: se estudiaron un total de 19 miembros. Se les realizó un protocolo diagnóstico que incluía un historia clínica detallada, junto con una hemograma y estudio de coagulación, una bioquímica amplia incluyendo pruebas de función hepática, estudio sérico del metabolismo del hierro, niveles circulantes de ácido fólico y vitamina B12, pruebas de función tiroidea, determinación de la transglutaminasa tisular y marcadores genéticos (DQ2 y DQ8). En los casos sospechosos y para su confirmación se realizó gastroscopia completada con toma de biopsias duodenales múltiples. Resultados: encontramos una prevalencia global de EC en 9/19 de los familiares estudiados, lo que representa un 47,4%, distribuidos de la siguiente manera en función del parentesco con el caso índice: cuatro de siete hermanos (57%); uno de tres hijos (33,3%); tres de ocho sobrinos (37,5%); y el único sobrino-nieto estudiado de nueve años de edad, también estaba afecto. Conclusiones: de todo ello se deduce la necesidad de hacer estudios amplios familiares, cada vez que se diagnostica un paciente de enfermedad celiaca, incluyendo familiares de primero y segundo grado, dada la relativa facilidad actual para llevarlos a cabo y la elevada prevalencia encontrada

Introduction: celiac disease (CD) is an autoimmune condition that is triggered by the ingestion of gluten, a substance present in most cereals, and that affects genetically predisposed individuals. As a result, this condition is clearly familial, and mainly associated with HLA class II markers. Objectives: in this work we set out to analyze the prevalence of CD in an extensive family based on an index subject who had already died from this disease a few years ago, where CD had been complicated by the development of a small-bowel malignancy, namely an adenocarcinoma. Methods: nineteen members were studied. They all were subjected to a diagnostic protocol including a detailed medical history, hemogram, coagulation tests, and blood biochemistry (including liver function tests, serum iron metabolism, circulating folic acid and vitamin B12 levels, thyroid function tests, tissue transglutaminase measurement, and genetic markers (DQ2 and DQ8). Suspect cases underwent gastroscopy plus multiple duodenal biopsy for confirmation. Results: overall we encountered CD in 9/19 studied members, which represents 47.4% with the following distribution according to degree of kinship –four of seven siblings (57%); one of three children (33.3%); three of eight nephews and nieces (37.5%), and the only grandnephew, who was 9 years old. Conclusions: from all this it may be seen that family studies are needed every time a patient is diagnosed with celiac disease; these studies should include both first- and second-degree relatives, given the high prevalence encountered and the fact that these tests are relatively straighforward to perform

Sequence variation divides Equine rhinitis B virus into three distinct phylogenetic groups that correlate with serotype and acid stability.

Equine rhinitis B virus (ERBV), genus Erbovirus, family Picornaviridae, occurs as two serotypes, ERBV1 and ERBV2, and the few isolates previously tested were acid labile. Of 24 ERBV1 isolates tested in the studies reported here, 19 were acid labile and five were acid stable. The two available ERBV2 isolates, as expected, were acid labile. Nucleotide sequences of the P1 region encoding the capsid proteins VP1, VP2, VP3 and VP4 were determined for five acid-labile and three acid-stable ERBV1 isolates and one acid-labile ERBV2 isolate. The sequences were aligned with the published sequences of the prototype acid-labile ERBV1.1436/71 and the prototype ERBV2.313/75. The three acid-stable ERBV1 were closely related in a phylogenetic group that was distinct from the group of six acid-labile ERBV1, which were also closely related to each other. The two acid-labile ERBV2 formed a third distinct group. One acid-labile ERBV1 had a chimeric acid-labile/acid-stable ERBV1 P1 sequence, presumably because of a recombination event within VP2 and this was supported by SimPlot analysis. ERBV1 rabbit antiserum neutralized acid-stable and acid-labile ERBV1 isolates similarly. Accordingly, three distinct phylogenetic groups of erboviruses exist that are consistent with serotype and acid stability phenotypes.

Retreatment and maintenance therapy with infliximab in fistulizing Crohn's disease.

OBJECTIVES: Infliximab has clearly demonstrated its efficacy in the short-term treatment of fistulizing Crohn's disease. We present here the results of retreatment and long-term maintenance therapy. PATIENTS AND METHODS: Eighty one consecutive patients with active fistulizing Crohn's disease, in whom previous treatments had failed, were treated with infliximab. All patients received as the initial treatment of 5 mg/kg i.v. infusions (weeks 0, 2, and 6). Those patients who failed to respond after the initial cycle (group 1, n = 25), or those who relapsed after having responded (group 2, n = 13), received retreatment with three similar doses (weeks 0,2, and 6). Those who responded to retreatment were included in a long-term maintenance programme (n = 44), with repeated doses (5 mg/kg i.v. infusions) every eight weeks for 1-2 years. RESULTS: In the initial treatment 56% of the patients responded partially; this response being complete in 44%. In the retreatment, 28% of group 1 (non-responders) presented a complete response, compared to 77% in group 2 (relapsers) (p < 0.0001). In the maintenance treatment, the global response was 88% (39/44). The mean number of doses per patient was 4.4 +/- 2 (range 1-9) with a duration of 36 +/- 12 weeks (range 8-72). Adverse effects were not significantly increased in either treatment. CONCLUSIONS: Both retreatment and long-term maintenance therapy with infliximab, are highly effective and well tolerated in fistulizing Crohn's disease patients.

Infliximab improves quality of life in the short-term in patients with fistulizing Crohn's disease in clinical practice.

OBJECTIVES: To assess the effect of infliximab on quality of life in a series of patients with fistulizing Crohn's disease. PATIENTS AND METHODS: A prospective observational study was made. A total of 25 patients with single or multiple draining abdominal or perianal fistulas were selected for the study. All received an intravenous infusion of infliximab at a dose of 5 mg per kilogram of body weight in weeks 0, 2, and 6. The clinical activity was calculated every two weeks over a 10-week follow-up. HRQOL (SF-36 and IBDQ scores) were compared at baseline and at weeks 4 and 10. RESULTS: Sixty-four percent of patients had a clinical response to treatment with infliximab, with complete closure of fistulas. The mean values of CDAI decreased during follow-up, with a significant difference between weeks 0 and 10 (p < 0.01). Health-related quality of life (HRQOL), as measured by means of SF-36, showed an overall improvement in the physical domain (PCS) after 4 and 10 weeks (p < 0.05). An increase was also observed in IBDQ overall score on comparing the results obtained at week 0 and week 4 (p < 0.01). The social functioning domain of IBDQ was not significantly changed with treatment. CONCLUSIONS: Treatment with infliximab in active fistulizing Crohn's disease results in a significant increase in the quality of life of patients at short-term.