Effusion-synovitis worsening mediates the association between body mass index and Kellgren-Lawrence progression in obese individuals: data from the Osteoarthritis Initiative.

OBJECTIVE: Both obesity and synovitis are independently associated with knee osteoarthritis (KOA) progression. We examined whether synovitis mediates the relationship between body mass index (BMI) and KOA radiographic progression in the Osteoarthritis Initiative (OAI) cohort. DESIGN: We conducted a case-control study within the OAI. Cases (n = 315) were right knees with an increase of ≥1 Kellgren-Lawrence from baseline to 48 months of follow-up. Controls (n = 315) were right knees with no KL change. Cases and controls were matched by age, sex, race, and baseline KL. MRI Osteoarthritis Knee Score (MOAKS) at baseline and at 2 years was used for a semi-quantitative scoring (0-3) of effusion-synovitis and Hoffa-synovitis. Conditional logistic regression estimated associations between BMI and synovitis with KOA progression. Mediation analysis was used to assess the mediating effects of synovitis. RESULTS: The mean age of participants was 61 years, 70.8% were women, and 87% were White. KOA progression was associated with higher BMI (adjusted OR 1.05; 95%CI 1.01-1.09) and effusion-synovitis relative to no effusion-synovitis (adjusted OR 2.2; 95%CI 1.6-3.1). Associations between effusion-synovitis worsening and KOA progression were more pronounced among obese individuals (OR 34.1; 95%CI 4.2-274.8; P = 0.001) compared to normal weight (OR 3.2; 95%CI 0.8-12.8, P=0.096) individuals. Effusion-synovitis at 2 years, but not at baseline, mediated the relationship between BMI and KOA progression over a 4-year period. CONCLUSIONS: We found that effusion-synovitis worsening mediated the association between BMI and KOA progression and was associated with increased risk of KOA progression, particularly among obese individuals.

Travel-associated Legionnaires' disease: would changing cluster definition lead to the prevention of a larger number of cases?

According to European Guidelines for Legionnaires' Disease prevention and control, travel-associated Legionnaires' disease (TALD) cases are managed differently if classified as sporadic or as part of a cluster and more stringent control measures are deployed after clusters are identified. In this study, we propose to modify the current cluster definition: 'two or more cases of Legionnaires' disease (LD) who stayed at, or visited, the same commercial accommodation site 2-10 days before onset of illness and whose onset is within the same 2-year period' with a new cluster definition, i.e. accommodation sites associated with multiple cases regardless of the time elapsed between them. TALD cases occurred in Italy and in the Balearic Islands between 2005 and 2015 were analysed applying the current European Legionnaires' Disease Surveillance Network (ELDSNet) cluster definition. In a sample of selected accommodation sites with multiple cases, a microbiological study was also conducted. Using the new definition, 63 additional sites (16.4% increase) and 225 additional linked cases (19.5% increase) were identified. Legionella pneumophila sg1 was isolated from 90.7% of the selected accommodation sites. The use of the here proposed TALD cluster definition would warrant a full investigation for each new identified case. This approach should therefore increase the number of sites that will require a risk assessment and, in the presence of an increased risk, the adoption of LD control measures to hopefully prevent additional cases.

Choline kinase inhibition in rheumatoid arthritis.

OBJECTIVES: Little is known about targeting the metabolome in non-cancer conditions. Choline kinase (ChoKα), an essential enzyme for phosphatidylcholine biosynthesis, is required for cell proliferation and has been implicated in cancer invasiveness. Aggressive behaviour of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA) led us to evaluate whether this metabolic pathway could play a role in RA FLS function and joint damage. METHODS: Choline metabolic profile of FLS cells was determined by (1)H magnetic resonance spectroscopy ((1)HMRS) under conditions of ChoKα inhibition. FLS function was evaluated using the ChoKα inhibitor MN58b (IC50=4.2 µM). For arthritis experiments, mice were injected with K/BxN sera. MN58b (3 mg/kg) was injected daily intraperitoneal beginning on day 0 or day 4 after serum administration. RESULTS: The enzyme is expressed in synovial tissue and in cultured RA FLS. Tumour necrosis factor (TNF) and platelet-derived growth factor (PDGF) stimulation increased ChoKα expression and levels of phosphocholine in FLS measured by Western Blot (WB) and metabolomic studies of choline-containing compounds in cultured RA FLS extracts respectively, suggesting activation of this pathway in RA synovial environment. A ChoKα inhibitor also suppressed the behaviour of cultured FLS, including cell migration and resistance to apoptosis, which might contribute to cartilage destruction in RA. In a passive K/BxN arthritis model, pharmacologic ChoKα inhibition significantly decreased arthritis in pretreatment protocols as well as in established disease. CONCLUSIONS: These data suggest that ChoKα inhibition could be an effective strategy in inflammatory arthritis. It also suggests that targeting the metabolome can be a new treatment strategy in non-cancer conditions.

Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

BACKGROUND: Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR) for detection of S. pneumoniae (9802 gene fragment), H. influenzae (omp P6 gene) and N. meningitidis (ctrA gene). The method was evaluated on bronchoalveolar lavage (BAL) samples from 156 adults with lower respiratory tract infection (LRTI) and 31 controls, and on 87 cerebrospinal fluid (CSF) samples from meningitis patients. RESULTS: The analytical sensitivity was not affected by using a combined mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae/N. meningitidis) in single tubes. By blood- and BAL-culture and S. pneumoniae urinary antigen test, S. pneumoniae and H. influenzae were aetiological agents in 21 and 31 of the LTRI patients, respectively. These pathogens were identified by qmPCR in 52 and 72 of the cases, respectively, yielding sensitivities and specificities of 95% and 75% for S. pneumoniae, and 90% and 65% for H. influenzae, respectively. When using a cut-off of 105 genome copies/mL for clinical positivity the sensitivities and specificities were 90% and 80% for S. pneumoniae, and 81% and 85% for H. influenzae, respectively. Of 44 culture negative but qmPCR positive for H. influenzae, 41 were confirmed by fucK PCR as H. influenzae. Of the 103 patients who had taken antibiotics prior to sampling, S. pneumoniae and H. influenzae were identified by culture in 6% and 20% of the cases, respectively, and by the qmPCR in 36% and 53% of the cases, respectively.In 87 CSF samples S. pneumoniae and N. meningitidis were identified by culture and/or 16 S rRNA in 14 and 10 samples and by qmPCR in 14 and 10 samples, respectively, giving a sensitivity of 100% and a specificity of 100% for both bacteria. CONCLUSIONS: The PCR provides increased sensitivity and the multiplex format facilitates diagnosis of S. pneumoniae, H. influenzae and N. meningitidis and the assay enable detection after antibiotic treatment has been installed. Quantification increases the specificity of the etiology for pneumonia.

Toward a quantitative DNA-based definition of pneumococcal pneumonia: a comparison of Streptococcus pneumoniae target genes, with special reference to the Spn9802 fragment.

The current shift from phenotypically toward genotypically based microbial diagnosis is not unproblematic. A novel quantitative real-time polymerase chain reaction (PCR) assay based on the Spn9802 DNA fragment was therefore developed for detection of Streptococcus pneumoniae. Out of 44 bacterial species, only S. pneumoniae and Streptococcus pseudopneumoniae were positive in Spn9802 PCR. In an evaluation on nasopharyngeal aspirates from 166 patients with community-acquired pneumonia, the assay was positive in 49 of 50 culture-positive cases. Of 19 culture-negative but Spn9802 PCR-positive cases, 12 were confirmed as S. pneumoniae by rnpB sequence analysis. With an expanded reference standard, including culture and rnpB sequencing, Spn9802 had a sensitivity of 94% and a specificity of 98%. A cutoff for clinically significant positivity was 10(4) DNA copies/mL, giving 71% sensitivity and 100% specificity. In conclusion, Spn9802 real-time PCR is highly sensitive and specific. The quantification it provides enables differentiation between pneumococcal pathogenicity and commensalism.

NK cell receptors involved in the response to human cytomegalovirus infection.

Human cytomegalovirus (HCMV) infection is a paradigm of the complexity reached by host-pathogen interactions. To avoid recognition by cytotoxic T lymphocytes (CTL) HCMV inhibits the expression of HLA class I molecules. As a consequence, engagement of inhibitory killer immunoglobulin-like receptors (KIR), CD94/NKG2A, and CD85j (ILT2 or LIR-1) natural killer cell receptors (NKR) specific for HLA class I molecules is impaired, and infected cells become vulnerable to an NK cell response driven by activating receptors. In addition to the well-defined role of the NKG2D lectin-like molecule, the involvement of other triggering receptors (i.e., activating KIR, CD94/NKG2C, NKp46, NKp44, and NKp30) in the response to HCMV is being explored. To escape from NK cell-mediated surveillance, HCMV interferes with the expression of NKG2D ligands in infected cells. In addition, the virus may keep NK inhibitory receptors engaged preserving HLA class I molecules with a limited role in antigen presentation (i.e., HLA-E) or, alternatively, displaying class I surrogates. Despite considerable progress in the field, a number of issues regarding the involvement of NKR in the innate immune response to HCMV remain uncertain.

Aseptic spondylodiskitis in rheumatic diseases.

Aseptic diskitis is relatively common. Several rheumatic diseases involving the spine may have this complication. As this condition mimic infectious diskitis, it is important to recognize it. Clinically, it is characterised by vertebral pain of an inflammatory nature, occasionally accompanied by fever and an increase in the erythrocyte sedimentation rate. Radiologically, the decrease in the articular space and the irregularity of the vertebral plates are of particular importance. Although uncommon, it is necessary to bear in mind this possibility when the etiological search for a possible infectious diskitis proves fruitless. A MEDLINE (1986-2000) and PUBMED (1966-2000) search of relevant articles was performed. Descriptors used were aseptic diskitis, spondylodiskitis, pseudodiskitis and pseudoarthrosis.

Gout and secondary amyloid.

A case of gout and secondary amyloid is described. This rare association is described and the literature is reviewed.

Occult liver involvement by polyarteritis nodosa.

The diagnosis of panarteritis nodosa is usually difficult because of the variability of clinical manifestations. Herein is presented a case of occult liver involvement by polyarteritis nodosa. Several biopsies were performed but the diagnosis was made with the contribution of a hepatic arteriography.

[The SAPHO syndrome: a study of 16 cases]. / Síndrome SAPHO: estudio de 16 casos.

The SAPHO syndrome is characterized by synovitis, acne, palmo-plantar pustulosis, hyperostosis and osteitis. SAPHO syndrome has been occasionally described in Spain. We present our experience of 16 cases with the SAPHO syndrome diagnosed between 1984-1995. The predominant clinical symptoms were: anterior thoracic pain (14 cases), sacroiliac pain (7 cases) and peripheral arthritis (2 cases). Cutaneous involvement was characterized by palmo-plantar pustulosis (8 cases) acne (3 cases) and psoriasis (2 cases). The histocompatibility antigen B27 was negative in all cases. A computerized tomographic study revealed involvement of sterno-costo-clavicular and manubriosternal joints (14 cases) and sacroiliitis (8 cases).

Encuesta sobre factores de riesgo de enfermedades crónicas no transmisibles en personal hospitalario que asistió a un curso de alimentación saludable / Survey on the risk factors of noncommunicable diseases in hospital personnel attending a course on healthy eating

Introducción: Las ECNT constituyen la principal causa de muerte en nuestro país y representan una epidemia en aumento. La prevención debe concentrarse contra los factores de riesgo prevenibles, el tabaquismo, mala alimentación, falta de actividad física y consumo excesivo de alcohol. Objetivo: Describir la situación de salud y factores de riesgo de ECNT del Personal del Hospital Garrahan que asistió al curso de Alimentación Saludable. Materiales y métodos: estudio descriptivo de corte transversal retrospectivo. Se realizó la encuesta "Situación de salud y factores de riesgo", por autorreporte durante el periodo 2015-2017. Los datos se analizaron con SPSS 20 para Windows. Resultados: Muestra de 194 alumnos, 81% mujeres. El 41.2% es universitario y el 50,8% no fuma. A mayor edad menor actividad física. Solo el 18% de la muestra cumplió con las recomendaciones de consumo de verduras y el 24% de frutas. El consumo de carne vacuna, supero la recomendación no así el pescado. El 31% siempre o casi siempre sobreagrega sal. El 70.1% toma de 1 a 4 vasos de agua, y solo el 6,34% más de 8 vasos. La prevalencia de exceso de peso fue del 53.6%. Las enfermedades metabólicas declaradas fueron del 39% entre HTA, colesterol alto y diabetes 2. Discusión: El exceso de peso, se correlaciona con el de la población argentina. Podría deberse al sedentarismo, y conductas alimentarias inadecuadas. Se observó que a medida que el IMC aumenta, el consumo de frutas, verduras y la realización de actividad física, disminuyen. Conclusión: Para crear nuevos hábitos alimentarios y de actividad física, es necesario información de calidad y herramientas para tomar acciones con responsabilidad sobre la mejora en el cuidado de su propia salud (AU)

Introduction: Noncommunicable diseases (NCDs) are the leading cause of death in our country and a growing epidemic. Prevention should focus on preventable risk factors, such as smoking, poor eating habits, and excessive alcohol intake. Objective: To describe health status and risk factors for NCDs in the personnel of Garrahan Hospital that attended a Healthy Eating course. Material and methods: A retrospective, cross-sectional, descriptive study. A selfreport survey "Health status and risk factors" was administered over the period 2015-2017. Data were analyzed using SPSS 20 for Windows. Results: The sample consisted of 194 pupils; 81% was female. Overall, 41.2% had university education and 50,8% did not smoke. The older the age, the less physical exercise. Only 18% of the sample met the recommendations for vegetable intake and 24% those for fruit intake. Cow meat consumption was higher than the recommendations, but fish consumption was not. Overall, 31% always or almost always added too much salt. Of the sample, 70.1% drank 1 to 4 glasses of water and only 6,34% drank more than 8 glasses of water. The prevalence of overweight was 53.6%. Metabolic diseases, among which AHT, high cholesterol, and diabetes 2, were reported in 39%. Discussion: The rate of overweight, correlating with the general Argentine population, may be due to a sedentary lifestyle and inadequate eating habits. It was observed that when the BMI was higher, fruit and vegetable intake and physical exercise were lower. Conclusion: To develop new eating habits and increase physical exercise, quality information and tools are necessary in order to take responsible action regarding improvements in personal health care (AU)

PCR detection of Haemophilus influenzae from respiratory specimens.

The detection of Haemophilus influenzae by conventional methods like culture is time-consuming and may give false-negative results, especially during ongoing antibiotic treatment. Therefore, non-culture based methods that are sensitive, specific, and rapid are valuable for early diagnosis and effective therapy. Here we describe a quantitative real-time PCR assay based on the outer membrane P6 gene omp6, to detect H. influenzae and its application on respiratory tract specimens.

Quantitative fucK gene polymerase chain reaction on sputum and nasopharyngeal secretions to detect Haemophilus influenzae pneumonia.

A quantitative polymerase chain reaction (PCR) for the fucK gene was developed for specific detection of Haemophilus influenzae. The method was tested on sputum and nasopharyngeal aspirate (NPA) from 78 patients with community-acquired pneumonia (CAP). With a reference standard of sputum culture and/or serology against the patient's own nasopharyngeal isolate, H. influenzae etiology was detected in 20 patients. Compared with the reference standard, fucK PCR (using the detection limit 10(5) DNA copies/mL) on sputum and NPA showed a sensitivity of 95.0% (19/20) in both cases, and specificities of 87.9% (51/58) and 89.5% (52/58), respectively. In a receiver operating characteristic curve analysis, sputum fucK PCR was found to be significantly superior to sputum P6 PCR for detection of H. influenzae CAP. NPA fucK PCR was positive in 3 of 54 adult controls without respiratory symptoms. In conclusion, quantitative fucK real-time PCR provides a sensitive and specific identification of H. influenzae in respiratory secretions.

Detection of Haemophilus influenzae in respiratory secretions from pneumonia patients by quantitative real-time polymerase chain reaction.

A quantitative real-time polymerase chain reaction (PCR) based on the omp P6 gene was developed to detect Haemophilus influenzae. Its specificity was determined by analysis of 29 strains of 11 different Haemophilus spp. and was compared with PCR assays having other target genes: rnpB, 16S rRNA, and bexA. The method was evaluated on nasopharyngeal aspirates from 166 adult patients with community-acquired pneumonia. When 10(4) DNA copies/mL was used as cutoff limit for the method, P6 PCR had a sensitivity of 97.5% and a specificity of 96.0% compared with the culture. Of 20 culture-negative but P6 PCR-positive cases, 18 were confirmed by fucK PCR as H. influenzae. Five (5.9%) of 84 nasopharyngeal aspirates from adult controls tested PCR positive. We conclude that the P6 real-time PCR is both sensitive and specific for identification of H. influenzae in respiratory secretions. Quantification facilitates discrimination between disease-causing H. influenzae strains and commensal colonization.

Paget's disease of bone in early adult life.

OBJECTIVE: To determine the range and activity of the clinical and biological features of patients aged <40 with Paget's disease of bone. METHODS: A retrospective two centre study of 314 patients with Paget's disease of bone from two university hospitals. The disease was diagnosed by radiological, serum alkaline phosphatase (AP) levels, or clinical features, and bone scintigraphy in most patients. Demographic data, reason for diagnosis, bones affected, disease extent using Coutris' index, complications during progression, and disease activity using Renier's index were assessed. Patients over and under 40 were compared. RESULTS: 18/314 (5.7%) patients were diagnosed before the age of 40; median (SD) age was 35.4 (5.5) (range 18-40) and AP 555.6 (566.3) IU/l (range 70-1949). Coutris' extension index was 12.8 (10.5) and Renier's activity index 35.9 (31.9). Younger patients had more affected bones (p<0.05) than those aged >40, higher level of extension (p<0.05), higher AP value (p = 0.05), and greater incidence of thoracolumbar spine disease. Disease activity did not differ significantly between the groups. CONCLUSIONS: Paget's disease diagnosed before the age of 40 is more extensive but not more active, with higher AP values than in those diagnosed after age 40.

Natural killer cell receptors for major histocompatibility complex class I and related molecules in cytomegalovirus infection.

Downmodulation of major histocompatibility complex (MHC) class I molecules by cytomegalovirus (CMV) impairs the engagement of specific leucocyte-inhibitory receptors, rendering infected cells vulnerable to natural killer (NK) cells. Members of the murine Ly49 and human KIR families, CD85j (ILT2 or leucocyte Ig-like receptor-1), as well as the CD94/NKG2A-inhibitory killer lectin-like receptor (KLR) fulfil this surveillance role. On the other hand, NK-activating receptors specific to ligands expressed on virus-infected cells may overcome the control by inhibitory receptors. In this regard, NKG2D and Ly49H lectin-like molecules trigger NK-cell functions recognizing, respectively class I-related stress-inducible molecules and the m157 murine CMV glycoprotein. Among a variety of immune evasion strategies, CMV promotes the synthesis of class I surrogates and selectively preserves the expression of some class I molecules in infected cells; moreover, CMV interferes with the expression of ligands for NKG2D. We herein review these aspects of the host-pathogen interaction, discussing a number of open issues.