228 research outputs found
Editorial: Autoinflammatory Diseases: From Genes to Bedside
The year 2019 marked the 20th anniversary of the formal recognition of autoinflammatory diseases as a distinct group of rheumatological conditions, following the identification of the gene mutated in patients with a dominantly inherited periodic fever known as familial Hibernian fever (FHF) (1). This nosological concept was introduced by one of the founders of the field, Dr. Daniel Kastner. Prior to this time, the only recognized periodic fever disease was familial Mediterranean fever (FMF) and patients presenting with similar symptoms, irrespective of inheritance pattern, were suspected to have a variant FMF. Most patients, with exception for FMF, were treated with NSAID, glucocorticoids alone, or in a combination with immunosuppressive agents. These chronic life-long conditions negatively impacted patients' quality of life and were associated with significant morbidity and mortality, partially due to treatment-related side effects. The early advances in the field of autoinflammation were driven by the ascertainment of families with inflammatory phenotypes segregating either as a recessive (FMF) or dominantly (FHF) inherited trait. This allowed for linkage mapping, positional cloning and candidate gene screening even before the completion of human genome sequencing project in 2003. These gene-hunting projects were laborious and time-consuming, but nonetheless successful and led to identification of the first three genes associated with autoinflammatory diseases: MEFV, TNFRSF1A, and CIAS1/NLRP3
Current therapeutic options for the main monogenic autoinflammatory diseases and PFAPA syndrome: evidence-based approach and proposal of a practical guide
Monogenic autoinflammatory diseases are rare conditions caused by genetic abnormalities affecting the innate immunity. Previous therapeutic strategies had been mainly based on results from retrospective studies and physicians' experience. However, during the last years, the significant improvement in their genetic and pathogenic knowledge has been accompanied by a remarkable progress in their management. The relatively recent identification of the inflammasome as the crucial pathogenic mechanism causing an aberrant production of interleukin 1β (IL-1β) in the most frequent monogenic autoinflammatory diseases led to the introduction of anti-IL-1 agents and other biologic drugs as part of the previously limited therapeutic armamentarium available. Advances in the treatment of autoinflammatory diseases have been favored by the use of new biologic agents and the performance of a notable number of randomized clinical trials exploring the efficacy and safety of these agents. Clinical trials have contributed to increase the level of evidence and provided more robust therapeutic recommendations. This review analyzes the treatment of the most frequent monogenic autoinflammatory diseases, namely, familial Mediterranean fever, tumor necrosis factor receptor-associated periodic fever syndrome, hyperimmunoglobulin D syndrome/mevalonate kinase deficiency, and cryopyrin-associated periodic syndromes, together with periodic fever with aphthous stomatitis, pharyngitis, and cervical adenitis syndrome, which is the most common polygenic autoinflammatory disease in children, also occurring in adult patients. Finally, based on the available expert consensus recommendations and the highest level of evidence of the published studies, a practical evidence-based guideline for the treatment of these autoinflammatory diseases is proposed
A retrospective analysis of 3 156 admissions with fever of unknown origin in a large Italian hospital
Background: fever of unknown origin (FUO) is defined as a fever with no etiologic diagnosis after standardized investigations performed during 3 days in hospital or after at least 3 ambulatory visits. Our study aims to describe the epidemiology of classic FUO through the retrospective analysis of 902 861 admissions to a large University Hospital in Italy, to investigate its temporal trend, and to evaluate differences between young and old patients.
Methods: we retrieved data records of all the admissions between the 1st January 1988 and 31st December 2007. Proportional admission rate (PAR ) of FUO was calculated. Time trends of FUO admissions were analysed by joinpoint regression, with time changes expressed as Expected Annual Percent Change (EA PC). The ICD 9-CM code was used to identify the diagnosis on discharge of FUO cases.
Results: in the study period 3 156 patients were admitted with a diagnosis of FUO (PAR=3.50 per 1 000). The time-trend analysis showed two joinpoints, the first in 1995 (EAPC of 307.80, 95% CI: 89.66-776.84, p=0.002), and the second in 1998 (EAPC=-8.57, 95% CI: -10.37-6.73; p<0.001). Around 22% of admissions remained without a definitive diagnosis of FUO, with this percentage being lower in patients ≥65 years compared with subjects aged 21-64.
Conclusions: FUO is a leading cause of admission to hospitals, as well as of morbidity and mortality, thus representing a challenge for diagnostic medicine and hospital care. It is necessary to develop a diagnostic methodology for FUO , so as to reduce costs of preventable hospitalizations
Plan de Cuidados Estandarizado para pacientes con Traqueostomía
La traqueostomía es una técnica quirúrgica cuyo objetivo es comunicar la tráquea con el exterior para establecer una vía aérea segura. El número de pacientes traqueostomizados ha aumentado en los últimos años: esta técnica presenta una morbilidad elevada del 10-33%, y su mortalidad oscila entre un 1-3%, la cual se ha reducido debido a los avances en el cuidado postoperatorio.El objetivo principal del trabajo ha sido eElaborar un plan de cuidados estandarizado actualizado enfocado en aplicar de forma sistemática cuidados integrales de enfermería adaptados al paciente traqueostomizado.<br /
Disease Phenotype and Outcome Depending on the Age at Disease Onset in Patients Carrying the R92Q Low-Penetrance Variant in TNFRSF1A Gene
Aparició en l'adult; Malalties autoinflamatòries; Variants de baixa penetrànciaAparición en el adulto; Enfermedades autoinflamatorias; Variantes de baja penetranciaAdult onset; Autoinflammatory diseases; Low-penetrance variantsBackground: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is an autosomal-dominant autoinflammatory disease caused by mutations in the TNFRSF1A gene. R92Q, a low-penetrance variant, is usually associated with a milder TRAPS phenotype than structural or pathogenic mutations. No studies differentiating R92Q-related disease in patients with pediatric and adult onset have been performed to date.
Objective: To analyze clinical features and disease outcomes in patients diagnosed with TRAPS associated with R92Q variant and to investigate differences between patients with pediatric and adult disease onset.
Methods: A retrospective review of patients with R92Q-related disease from four reference centers for autoinflammatory diseases was performed. Clinical and laboratory features, family history of autoinflammatory diseases, treatments received, and outcomes during follow-up were recorded and separately analyzed in pediatric and adult patients. Our results were included in the analysis with other reported pediatric and adult R92Q-related disease series.
Results: Our series encompassed 18 patients (9 females and 9 males) with R92Q variant. In 61% of patients, disease onset occurred during infancy and in 39%, during adulthood, with a median diagnostic delay of 5 years and a follow-up of 5.4 years. A positive family history of autoinflammatory disease was detected in 28% of patients. All patients presented with febrile recurrent episodes. Other common symptoms included arthralgia/arthritis (61%), myalgia (39%), asthenia/fatigue (44%), abdominal pain (39%), headache (33%), odynophagia (33%), skin rash (28%), and chest pain (22%). During attacks, 80% of patients increased acute phase reactants levels. No patient had developed amyloidosis during the study period. At the end of follow-up, 28% of patients were asymptomatic and treatment free, 50% were receiving non-steroidal anti-inflammatory drugs or glucocorticoids on demand, and 22% were being treated with biologic agents. When differences between pediatric and adult patients were globally analyzed, adults tended to have longer attacks duration and presented more frequently with chest pain and headache, while abdominal pain, vomiting, cervical adenitis, and pharyngitis predominated in pediatric patients. No differences in outcomes and treatment requirements were observed in both age groups.
Conclusion: This study has contributed to characterize R92Q-related disease by identifying trends in disease phenotypes depending on the age at disease onset.This study has been supported by Ministerio de Economía y Competitividad (SAF 14/57708-R) and co-funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, and Una manera de hacer Europa (JH-R)
Higher Frequencies of Lymphocytes Expressing the Natural Killer Group 2D Receptor in Patients With Behçet Disease
Behçet disease (BD) is an inflammatory systemic disease with a fluctuating course, which can affect the skin, eyes, central nervous system, musculoskeletal, gastrointestinal, and vascular systems. No laboratory tests are currently available for the diagnosis of BD and monitoring disease activity. Moreover there is a lack of knowledge on BD pathogenesis. This study focused on circulating Natural Killer (NK), NKT and T cells evaluated as CD3neg CD56pos, CD3pos CD56pos, and CD3pos CD56neg. Peripheral blood mononuclear cells (PBMCs) were collected from 38 BD patients and 20 healthy controls (HC). The frequencies of NK, NKT, and T cells expressing CD16, CD69, NKG2D, Nkp30, Nkp46, and NKG2A were assessed by flow cytometry. Cytotoxic potential of NK cells was evaluated by flow cytometry as the percentage of cells expressing the degranulation marker CD107a after incubation with K562 cells. The levels of 27 cytokines were determined in plasma with a multiplex bead-based assay. Higher percentages of NK, NKT, and T cells expressing NKG2D were detected in PBMCs of BD patients than HC. ROC curve analysis showed that the evaluation of NKG2Dpos NK, NKT, and T cell percentages discriminated between BD patients and HC. Moreover, there was a positive correlation between the BD Current Activity Form (BDCAF) scores and the frequencies of NKG2Dpos NK and NKT cells. A higher frequency of NK cells expressing CD107a was induced in PBMCs from BD patients than HC after incubation with K562 cells. Concentrations of IL-5, IL-6, IL-10, IL-13, IP-10, and MIP-1β were higher in plasma of BD patients than HC. Monitoring the frequencies of NKG2Dpos lymphocytes could help the clinicians in BD patients management. In addition, the increased expression of NKG2D in BD patients is likely involved in disease pathogenesis
Genomics and Phylogeny of Rhodotorula glutinis and Rhodotorula kratochvilovae Isolated from the Northern Peruvian Andes
Genomes of oleaginous yeast strains Rhodotorula glutinis CON-5 and Rhodotorula kratochvilovae POR-3, isolated from areas in the northern Peruvian Andes using SPAdes, were sequenced and assembled applying Illumina and de novo. Genomes of 20,515,696 and 20,738,185 bp, respectively, were determined. From the structural and functional annotations, the Basidiomycota phylum showed a similarity of 76.8% and 86.5% with 6,976 and 8,124 pairs of proteins in both yeasts respectively, with homologues in the UniProt data bank. Using OrthoVenn, a relationship between both yeasts was obtained from 450 orthologous groups. Likewise, the above-mentioned yeasts and R. toruloides (oleaginous Basidiomycota) showed 1,574 orthologous groups, indicating a good relationship. Construction of phylogenetic trees of genes encoding metabolic enzymes was also carried out, based on the ITS sequences which showed that CON-5 and POR-3 have a greater relationship with R. graminis. Their phylogenetic relationship was ascertained and determined that the enzymes involved in the metabolism of CON-5 and POR-3 are related to each other. It was also found that the protein sequences of the Basidiomycota phylum differ from Ascomycota. The study showed functional evidence regarding the lipid accumulation phenotype, an important aspect in the context of obtaining lipids or oleochemicals
New nanotechnologies for the treatment and repair of skin burns infections
Burn wounds are highly debilitating injuries, with significant morbidity and mortality rates worldwide. In association with the damage of the skin integrity, the risk of infection is increased, posing an obstacle to healing and potentially leading to sepsis. Another limitation against healing is associated with antibiotic resistance mainly due to the use of systemic antibiotics for the treatment of localized infections. Nanotechnology has been successful in finding strategies to incorporate antibiotics in nanoparticles for the treatment of local wounds, thereby avoiding the systemic exposure to the drug. This review focuses on the most recent advances on the use of nanoparticles in wound dressing formulations and in tissue engineering for the treatment of burn wound infections.The authors would like to thank the financial support received from Portuguese Science and Technology Foundation (FCT/MCT) and from European Funds (PRODER/COMPETE) under the project references M-ERA-NET/0004/2015-PAIRED and UIDB/04469/2020, co-financed by FEDER, under the Partnership Agreement PT2020.info:eu-repo/semantics/publishedVersio
Role of colchicine treatment in Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS): real-life data from the AIDA Network
Objective: To analyze the potential role of colchicine monotherapy in patients with tumor necrosis factor receptor associated periodic syndrome (TRAPS) in terms of control of clinical and laboratory manifestations. Methods: Patients with TRAPS treated with colchicine monotherapy were retrospectively enrolled; demographic, clinical and therapeutic data were collected and statistically analysed after having clustered patients according to different times at disease onset, penetrance of mutations, dosage of colchicine, and different disease manifestations. Results: 24 patients (14 males; 15 with pediatric disease onset) treated with colchicine monotherapy were enrolled. Colchicine resulted in a complete response in 3 (12.5%) cases, partial response in 14 (58.3%) patients, and lack of response in 7 (29.2%) patients. There were not significant differences in colchicine response between pediatric and adult disease onset (p = 0.42), between low- and high-penetrance mutations (p = 0.62), and according to different dosages (p = 0.66). No significant differences were identified in the frequency of specific disease manifestations between patients experiencing any response to colchicine and patients with lack of response. Conclusions: Colchicine monotherapy is useful in a low percentage of TRAPS patients; nevertheless, it could be attempted in patients with milder phenotypes and at a lower risk of developing reactive amyloidosis
Burden of disease from exposure to secondhand smoke in children in Europe
Background Secondhand smoke (SHS) exposure at home and fetal SHS exposure during pregnancy are a major cause of disease among children. The aim of this study is quantifying the burden of disease due to SHS exposure in children and in pregnancy in 2006–2017 for the 28 European Union (EU) countries. Methods Exposure to SHS was estimated using a multiple imputation procedure based on the Eurobarometer surveys, and SHS exposure burden was estimated with the comparative risk assessment method using meta-analytical relative risks. Data on deaths and disability-adjusted life years (DALYs) were collected from National statistics and from the Global Burden of Disease Study. Results Exposure to SHS and its attributable burden stalled in 2006–2017; in pregnant women, SHS exposure was 19.8% in 2006, 19.1% in 2010, and 21.0% in 2017; in children it was 10.1% in 2006, 9.6% in 2010, and 12.1% in 2017. In 2017, 35,633 DALYs among children were attributable to SHS exposure in the EU, mainly due to low birth weight. Conclusions Comprehensive smoking bans up to 2010 contributed to reduce SHS exposure and its burden in children immediately after their implementation; however, SHS exposure still occurs, and in 2017, its burden in children was still relevant
- …