What urethrogram sees and a surgeon does not. / Lo que una uretrografía ve y un cirujano no.

INTRODUCTION: Urethrorrhagia is an infrequent sign in childhood. It should be distinguished from hematuria, since they have a different etiology. CLINICAL CASE: 11-year-old male patient with significant urethrorrhagia. Urinary sediment analysis: red blood cells++. Pelvic ultrasonography: fusiform anechoic image in the corpus spongiosum of the penile root. Retrograde urethrogram: normal anterior urethra, extraluminal contrast passage in the ventral aspect of the bulbar urethra. Cystoscopy: no pathological findings in the urethra or the bladder. Control retrograde urethrogram: cystic dilatation of Cowper's gland duct; Maizels' type 3 perforated syringocele. DISCUSSION: Cowper's syringocele is a rare pathology. It can occur at any stage of childhood in the form of urinary infection, obstructive voiding symptoms, or urethrorrhagia. Urethrogram is key for diagnostic purposes, since most Cowper's syringoceles are detected following urethrogram or cystoscopy. Cases with functional repercussions for the urinary system require surgical treatment. Otherwise, a wait-and-see approach is feasible.

INTRODUCCION: La uretrorragia es un signo infrecuente en la infancia que debe distinguirse de la hematuria dada la diferente etiología de las mismas. CASO CLINICO: Varón de 11 años con uretrorragia franca. Sedimento urinario: hematíes++. Ecografía pélvica: imagen anecoica fusiforme en cuerpo esponjoso de raíz peneana. Uretrografía retrógrada: uretra anterior normal, paso de contraste extraluminal ventral en uretra bulbar. Cistoscopia: sin hallazgos patológicos en uretra ni vejiga. Uretrografía retrógrada de control: dilatación quística del conducto de las glándulas de Cowper; siringocele perforado tipo 3 de Maizels. COMENTARIOS: El siringocele de Cowper es una patología infrecuente que puede debutar en cualquier momento de la infancia como infección urinaria, síntomas miccionales obstructivos o uretrorragia. La uretrografía es fundamental en su diagnóstico ya que la mayoría se objetivan por este medio o cistoscopia. Los casos con repercusión funcional del sistema urinario requieren tratamiento quirúrgico. En caso contrario podrá realizarse actitud expectante.

Lo que una uretrografía ve y un cirujano no / What urethrogram sees and a surgeon does not

Introducción: La uretrorragia es un signo infrecuente en la infancia que debe distinguirse de la hematuria dada la diferente etiología de lasmismas. Caso clínico: Varón de 11 años con uretrorragia franca. Sedimento urinario: hematíes++. Ecografía pélvica: imagen anecoica fusiforme en cuerpo esponjoso de raíz peneana. Uretrografía retrógrada: uretra anterior normal, paso de contraste extraluminal ventral en uretra bulbar.Cistoscopia: sin hallazgos patológicos en uretra ni vejiga. Uretrografíaretrógrada de control: dilatación quística del conducto de las glándulasde Cowper; siringocele perforado tipo 3 de Maizels.Comentarios: El siringocele de Cowper es una patología infrecuente que puede debutar en cualquier momento de la infancia como infección urinaria, síntomas miccionales obstructivos o uretrorragia.La uretrografía es undamental en su diagnóstico ya que la mayoría se objetivan por este medio o cistoscopia. Los casos con repercusión funcional del sistema urinario requieren tratamiento quirúrgico. En caso ontrario podrá realizarse actitud expectante.

Introduction: Urethrorrhagia is an infrequent sign in childhood. It should be distinguished from hematuria, since they have a different etiology.Clinical case: 11-year-old male patient with significant urethror-rhagia. Urinary sediment analysis: red blood cells++. Pelvic ultrasonog-raphy: fusiform anechoic image in the corpus spongiosum of the penileroot. Retrograde urethrogram: normal anterior urethra, extraluminal con-trast passage in the ventral aspect of the bulbar urethra. Cystoscopy: nopathological findings in the urethra or the bladder. Control retrograde urethrogram: cystic dilatation of Cowper’s gland duct; Maizels’ type 3perforated syringocele.Discussion: Cowper’s syringocele is a rare pathology. It can occurat any stage of childhood in the form of urinary infection, obstructivevoiding symptoms, or urethrorrhagia. Urethrogram is key for diagnos-tic purposes, since most Cowper’s syringoceles are detected followingurethrogram or cystoscopy. Cases with functional repercussions for theurinary system require surgical treatment. Otherwise, a wait-and-seeapproach is feasible

Valoración de la eficacia analgésica del bloqueo facetario lumbar en función de la técnica de imagen utilizada: ecografía frente a fluoroscopia / Evaluation of the analgesic efficacy of lumbar facet block as a function of the imaging technique used: ultrasound versus fluoroscopy

Objetivo: En la lumbalgia mecánica por síndrome facetario lumbar están indicadas como opciones terapéuticas los bloqueos periarticulares e intrarticulares de las articulaciones facetarias lumbares, así como el bloqueo nervioso del ramo medial de la raíz o ramo posterior del nervio raquídeo. El bloqueo nervioso del ramo medial puede llevarse a cabo mediante control ecográfico o radioscópico. El objetivo de este estudio es valorar si existen diferencias en la eficacia analgésica del bloqueo en función de la técnica de imagen con la que se lleva a cabo (ecografía frente a radioscopia-fluoroscopia). Pacientes y método: Se ha realizado un estudio clínico transversal durante el mes de noviembre de 2020, analizando los bloqueos facetarios realizados en la Unidad del Dolor del Hospital Universitario Clínico de Salamanca entre mayo de 2018 y septiembre de 2020. La muestra analizada cuenta con 315 pacientes, de los cuales 212 fueron sometidos a bloqueo facetario ecoguiado en consulta y 103 se realizaron bajo control radioscópico en el quirófano. Se ha evaluado la medida del dolor inicial, previo al bloqueo, mediante la escala analógica visual (EVA inicial), así como la EVA final y el porcentaje de mejoría subjetiva recogido en los 15 días posteriores a la realización de la intervención, valorando sus diferencias en función de la técnica de imagen empleada para su realización. Resultados: Los valores de EVA final de los pacientes que se realizaron el bloqueo mediante radioscopia y la de aquellos que lo realizaron ecoguiado fue similar, con un resultado final de 3,5 (mediana), así como el porcentaje de mejoría subjetiva que también fue similar en ambos grupos, alcanzando esta el 50 %. Conclusiones: No existen diferencias en la eficacia analgésica del bloqueo facetario lumbar en función de la técnica de imagen empleada para su realización: radioscopia-fluoroscopia o ecografía.(AU)

Objective: In mechanical low back pain due to lumbar facet syndrome, periarticular and intra-articular blocks of the lumbar facet joints as well as nerve blocks of the medial branch of the spinal nerve root or posterior branch of the spinal nerve are indicated as therapeutic options. The nerve block of the medial branch can be performed by ultrasound or radioscopic monitoring. The aim of this study is to assess whether there are differences in the analgesic efficacy of the block depending on the imaging technique used (ultrasound versus fluoroscopic-radioscopy). Patients and method: A cross-sectional clinical study was conducted during the month of November 2020, analysing the facet blocks performed in the Pain Unit of the Hospital Universitario Clínico de Salamanca between May 2018 and September 2020. The sample analysed consisted of 315 patients, of whom 212 underwent an echo-guided facet block in consultation and 103 were performed under radioscopic control in the operating theatre. The initial pain measurement, prior to the block, was evaluated using the visual analogue scale (initial VAS), as well as the final VAS and the percentage of subjective improvement recorded 15 days after the intervention, assessing the differences according to the imaging technique used for its performance. Results: The final VAS values of the patients who underwent radioscopic block and those who underwent echo-guided block were similar, with a final result of 3.5 (median), as was the percentage of subjective improvement, which was also similar in both groups, reaching 50 %. Conclusions: There are no differences in the analgesic efficacy of the lumbar facet block depending on the imaging technique used for its performance: fluoroscopy-radioscopy or ultrasound.(AU)

C-Reactive protein and SOFA scale: A simple score as early predictor of critical care requirement in patients with COVID-19 pneumonia in Spain.

OBJECTIVE: To identify potential markers at admission predicting the need for critical care in patients with COVID-19 pneumonia. MATERIAL AND METHODS: An approved, observational, retrospective study was conducted between March 15 to April 15, 2020. 150 adult patients aged less than 75 with Charlson comorbidity index ≤6 diagnosed with COVID-19 pneumonia were included. Seventy-five patients were randomly selected from those admitted to the critical care units (critical care group [CG]) and seventy-five hospitalized patients who did not require critical care (non-critical care group [nCG]) represent the control group. One additional cohort of hospitalized patients with COVID-19 were used to validate the score. MEASUREMENTS AND MAIN RESULTS: Multivariable regression showed increasing odds of in-hospital critical care associated with increased C-reactive protein (CRP) (odds ratio 1.052 [1.009-1.101]; P = 0.0043) and higher Sequential Organ Failure Assessment (SOFA) score (1.968 [1.389-2.590]; P < 0.0001), both at the time of hospital admission. The AUC-ROC for the combined model was 0.83 (0.76-0.90) (vs AUC-ROC SOFA P < 0.05). The AUC-ROC for the validation cohort was 0.89 (0.82-0.95) (P > 0.05 vs AUC-ROC development). CONCLUSION: Patients COVID-19 presenting at admission SOFA score ≥ 2 combined with CRP ≥ 9.1 mg/mL could be at high risk to require critical care.

C-Reactive protein and SOFA scale: A simple score as early predictor of critical care requirement in patients with COVID-19 pneumonia in Spain. / Proteína C reactiva y escala SOFA: una simple escala como factor predictivo temprano de la necesidad de cuidados críticos en los pacientes con neumonía causada por COVID-19 en España.

OBJECTIVE: To identify potential markers at admission predicting the need for critical care in patients with COVID-19 pneumonia. MATERIAL AND METHODS: An approved, observational, retrospective study was conducted between March 15 to April 15, 2020. 150 adult patients aged less than 75 with Charlson comorbidity index ≤6 diagnosed with COVID-19 pneumonia were included. Seventy-five patients were randomly selected from those admitted to the critical care units (critical care group [CG]) and seventy-five hospitalized patients who did not require critical care (non-critical care group [nCG]) represent the control group. One additional cohort of hospitalized patients with COVID-19 were used to validate the score. MEASUREMENTS AND MAIN RESULTS: Multivariable regression showed increasing odds of in-hospital critical care associated with increased C-reactive protein (CRP) (odds ratio 1.052 [1.009-1.101]; P=.0043) and higher Sequential Organ Failure Assessment (SOFA) score (1.968 [1.389-2.590]; P<.0001), both at the time of hospital admission. The AUC-ROC for the combined model was 0.83 (0.76-0.90) (vs AUC-ROC SOFA P<.05). The AUC-ROC for the validation cohort was 0.89 (0.82-0.95) (P>0.05 vs AUC-ROC development). CONCLUSION: Patients COVID-19 presenting at admission SOFA score ≥2 combined with CRP ≥9,1mg/mL could be at high risk to require critical care.

[C-Reactive protein and SOFA scale: A simple score as early predictor of critical care requirement in patients with COVID-19 pneumonia in Spain]. / Proteína C reactiva y escala SOFA: una simple escala como factor predictivo temprano de la necesidad de cuidados críticos en los pacientes con neumonía causada por COVID-19 en España.

OBJECTIVE: To identify potential markers at admission predicting the need for critical care in patients with COVID-19 pneumonia. MATERIAL AND METHODS: An approved, observational, retrospective study was conducted between March 15 to April 15, 2020. 150 adult patients aged less than 75 with Charlson comorbidity index ≤ 6 diagnosed with COVID-19 pneumonia were included. Seventy-five patients were randomly selected from those admitted to the critical care units (critical care group [CG]) and seventy-five hospitalized patients who did not require critical care (non-critical care group [nCG]) represent the control group. One additional cohort of hospitalized patients with COVID-19 were used to validate the score. MEASUREMENTS AND MAIN RESULTS: Multivariable regression showed increasing odds of in-hospital critical care associated with increased C-reactive protein (CRP) (odds ratio 1.052 [1.009-1.101]; P = .0043) and higher Sequential Organ Failure Assessment (SOFA) score (1.968 [1.389-2.590]; P < .0001), both at the time of hospital admission. The AUC-ROC for the combined model was 0.83 (0.76-0.90) (vs AUC-ROC SOFA P < .05). The AUC-ROC for the validation cohort was 0.89 (0.82-0.95) (P > 0.05 vs AUC-ROC development). CONCLUSION: Patients COVID-19 presenting at admission SOFA score ≥ 2 combined with CRP ≥ 9,1 mg/mL could be at high risk to require critical care.

Renal Doppler ultrasound resistive index vs. renal scintigraphy with 99mTc-DTPA as diagnostic test for ureteropelvic junction obstruction in children. / Ecografía Doppler renal con medición de índices de resistencia vs. gammagrafía renal con 99mTc-DTPA para el diagnóstico de estenosis ureteropiélica en niños.

OBJECTIVE: A cross-sectional study was carried out with the objective of evaluating the usefulness of Doppler ultrasound with resistive index (RI) measure compared with renal scintigraphy with 99mTc-DTPA in children with unilateral ureteropelvic junction obstruction. METHODS: The study included children under 15 years with a diagnosis of unilateral ureteropelvic junction obstruction, healthy contralateral kidney with or without an antecedent of ureteropyeloplasty. The selected patients were sent to the Nuclear Medicine Department to carry out a renal scintigraphy with 99mTc-DTPA and days later were sent to the Radiology Department for the performance of Renal Doppler Ultrasound with RI. RESULTS: A total of 21 patients were included in the study, 15 males and 6 females, representing 71.4% and 28.6%, respectively. Mean age was 5.3 years. Only 3 had an antecedent of ureteropyeloplasty in the affected kidney. The scintigraphy reported data of unilateral obstruction in 18 patients, including the 3 patients with previous surgery. The average glomerular filtration rate (GFR) obtained with the scintigraphy was 100.28ml/min. The average GFR in affected kidneys was 43.03ml/min and 57.24ml/min in healthy kidneys (p<.001). Doppler ultrasound with RI reported ectasia in 100% of the affected kidneys and one normal contralateral kidney. The average RI in affected kidneys was 0.69mm/s and 0.50mm/s in healthy kidneys (p<.001). CONCLUSIONS: With the results obtained, we can suggest that ultrasound Doppler with measurement of RI can be an alternative tool to renal scintigraphy with 99mTc-DTPA in some cases.

The anti-CD6 antibody itolizumab provides clinical benefit without lymphopenia in rheumatoid arthritis patients: results from a 6-month, open-label Phase I clinical trial.

Itolizumab is a humanized anti-CD6 monoclonal antibody (mAb) that has previously shown encouraging results, in terms of safety and positive clinical effects, in a 6-week monotherapy clinical trial conducted in rheumatoid arthritis (RA) patients. The current Phase I study evaluated the safety and clinical response for a longer treatment of 12 itolizumab intravenous doses in subjects with active RA despite previous disease-modifying anti-rheumatic drug (DMARD) therapy. Twenty-one subjects were enrolled into four dosage groups (0·1, 0·2, 0·4 and 0·8 mg/kg). Efficacy end-points including American College of Rheumatology (ACR)20, ACR50 and ACR70 response rates and disease activity score in 28 joints (DAS28) were monitored at baseline and at specific time-points during a 10-week follow-up period. Itolizumab was well tolerated up to the highest tested dose. No related serious adverse events were reported and most adverse events were mild. Remarkably, itolizumab treatment did not produce lymphopenia and, therefore, was not associated with infections. All patients achieved a clinical response (ACR20) at least once during the study. Eleven subjects (55%) achieved at least a 20% improvement in ACR just 1 week after the first itolizumab administration. The clinical response was observed from the beginning of the treatment and was sustained during 24 weeks. The efficacy profile of this 12-week treatment was similar to that of the previous study (6-week treatment). These results reinforce the safety profile of itolizumab and provide further evidence on the clinical benefit from the use of this anti-CD6 mAb in RA patients.

Safety and efficacy of a basal-plus regimen with insulin glargine and insulin glulisine for elderly patients with high cardiovascular risk and type 2 diabetes mellitus. / Eficacia y seguridad de una pauta basal plus con insulina glargina e insulina glulisina en pacientes ancianos de alto riesgo cardiovascular con diabetes mellitus tipo 2.

OBJECTIVES: To assess the safety and efficacy of a basal-plus (BP) regimen with insulin glargine (as basal insulin) and insulin glulisine (as prandial insulin) with the main meal for elderly patients with type 2 diabetes mellitus (DM2) and high cardiovascular risk, following standard clinical practice. PATIENTS AND METHODS: An observational, retrospective study was conducted in 21 centres of internal medicine in Spain. The study included patients aged 65 years or older with DM2, undergoing treatment with a BP regimen for 4 to 12 months before inclusion in the study and a diagnosis of cardiovascular disease or high cardiovascular risk. The primary endpoint was the change in glycated haemoglobin (HbA1c) from the introduction of the glulisine to inclusion in the study. RESULTS: The study included 198 patients (mean age, 74±6.4 years; males, 52%). After at least 4 months of treatment with the BP regimen, started with the addition of glulisine, the mean HbA1c value decreased significantly (9±1.5% vs. 7.7±1.1%; P<.001), and almost 24% of the patients reached HbA1c levels of 7.5-8%. Furthermore, blood glucose levels under fasting conditions decreased significantly (190.6±73.2mg/dl vs. 138.9±38.2mg/dl; P<.001). A total of 35 patients (17.7%) had some hypoglycaemia during the month prior to the start of the study, and 2 cases (1.01%) of severe hypoglycaemia were detected. CONCLUSIONS: The BP strategy could significantly improve blood glucose control in patients 65 years of age or older with DM2 and high cardiovascular risk and is associated with a low risk of severe hypoglycaemia.

Should tumour necrosis factor antagonist safety information be applied from patients with rheumatoid arthritis to psoriasis? Rates of serious adverse events in the prospective rheumatoid arthritis BIOBADASER and psoriasis BIOBADADERM cohorts.

BACKGROUND: Information on the safety of tumour necrosis factor (TNF) antagonists frequently arises from their use in rheumatic diseases, their first approved indications, and is later applied to psoriasis. Whether the risk of biological therapy is similar in psoriasis and rheumatoid arthritis has been considered a priority research question. OBJECTIVES: To compare the safety profile of anti-TNF drugs in patients with rheumatoid arthritis and psoriasis. METHODS: We compared two prospective safety cohorts of patients with rheumatoid arthritis and psoriasis that share methods (BIOBADASER and BIOBADADERM). RESULTS: There were 1248 serious or mortal adverse events in 16 230 person-years of follow-up in the rheumatoid arthritis cohort (3171 patients), and 124 in the 2760 person-years of follow-up of the psoriasis cohort (946 patients). Serious and mortal adverse events were less common in patients with psoriasis than in rheumatoid arthritis (incidence rate ratio of serious adverse events in psoriasis/rheumatoid arthritis: 0·6, 95% confidence interval 0·5-0·7). This risk remained after adjustment for sex, age, treatment, disease, hypertension, diabetes, hypercholesterolaemia and simultaneous therapy with methotrexate (hazard ratio 0·54, 95% confidence interval 0·47-0·61), and after excluding patients receiving corticosteroids. Patients with rheumatoid arthritis showed a higher rate of infections, cardiac disorders, respiratory disorders and infusion-related reactions, whereas patients with psoriasis had more skin and subcutaneous tissue disorders and hepatobiliary disorders. CONCLUSIONS: Patients with rheumatoid arthritis clinical practice have almost double the risk of serious adverse events compared with patients with psoriasis, with a different pattern of adverse events. Safety data from rheumatoid arthritis should not be fully extrapolated to psoriasis. These differences are likely to apply to other immune-mediated inflammatory diseases.

Rheumatoid Arthritis Patients after Initiation of a New Biologic Agent: Trajectories of Disease Activity in a Large Multinational Cohort Study.

BACKGROUND: Response to disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA) is often heterogeneous. We aimed to identify types of disease activity trajectories following the initiation of a new biologic DMARD (bDMARD). METHODS: Pooled analysis of nine national registries of patients with diagnosis of RA, who initiated Abatacept and had at least two measures of disease activity (DAS28). We used growth mixture models to identify groups of patients with similar courses of treatment response, and examined these patients' characteristics and effectiveness outcomes. FINDINGS: We identified three types of treatment response trajectories: 'gradual responders' (GR; 3576 patients, 91·7%) had a baseline mean DAS28 of 4·1 and progressive improvement over time; 'rapid responders' (RR; 219 patients, 5·6%) had higher baseline DAS28 and rapid improvement in disease activity; 'inadequate responders' (IR; 103 patients, 2·6%) had high DAS28 at baseline (5·1) and progressive worsening in disease activity. They were similar in baseline characteristics. Drug discontinuation for ineffectiveness was shorter among inadequate responders (p=0.03), and EULAR good or moderate responses at 1year was much higher among 'rapid responders' (p<0.001). INTERPRETATION: Clinical information and baseline clinical characteristics do not allow a reliable prediction of which trajectory the patients will follow after bDMARD initiation.

Brief Report: Association of Rheumatoid Factor and Anti-Citrullinated Protein Antibody Positivity With Better Effectiveness of Abatacept: Results From the Pan-European Registry Analysis.

OBJECTIVE: To investigate the role of rheumatoid factor (RF) status and anti-citrullinated peptide antibody (ACPA) status as predictors of abatacept (ABA) effectiveness in patients with rheumatoid arthritis (RA). METHODS: We conducted a pooled analysis of data from 9 observational RA registries in Europe (ARTIS [Sweden], ATTRA [Czech Republic], BIOBADASER [Spain], DANBIO [Denmark], GISEA [Italy], NOR-DMARD [Norway], ORA [France], Reuma.pt [Portugal], and SCQM-RA [Switzerland]). Inclusion criteria were a diagnosis of RA, initiation of ABA treatment, and available information on RF and/or ACPA status. The primary end point was continuation of ABA treatment. Secondary end points were ABA discontinuation for ineffectiveness or adverse events and response rates at 1 year (good or moderate response according to the European League Against Rheumatism criteria with LUNDEX adjustment for treatment continuation). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the study end points in relation to RF and ACPA status were calculated. RESULTS: We identified 2,942 patients with available data on RA-associated autoantibodies; data on RF status were available for 2,787 patients (77.0% of whom were RF positive), and data on ACPA status were available for 1,903 patients (71.3% of whom were ACPA positive). Even after adjustment for sociodemographic and disease- and treatment-related confounders, RF and ACPA positivity were each associated with a lower risk of ABA discontinuation for any reason (HR 0.79 [95% CI 0.69-0.90], P < 0.001 and HR 0.78 [95% CI 0.68-0.90], P < 0.001, respectively), compared to RF-negative and ACPA-negative patients. Similar associations with RF and ACPA were observed for discontinuation of ABA treatment due to ineffectiveness, with HRs of 0.72 (95% CI 0.61-0.84) and 0.74 (95% CI 0.62-0.88), respectively (both P < 0.001). CONCLUSION: Our results strongly suggest that positivity for RF or ACPA is associated with better effectiveness of ABA therapy.

IL-6 blockade reverses the abnormal STAT activation of peripheral blood leukocytes from rheumatoid arthritis patients.

Considering the interplay of multiple STATs in response to cytokines, we investigated how IL-6 and its blocking affect STAT signaling in rheumatoid arthritis (RA). Leukocytes obtained from RA patients before and after tocilizumab treatment and healthy donors (HDs) were cytokine-stimulated and STAT phosphorylation was analyzed by cytometry. RA patients had significantly fewer pSTAT1+, pSTAT3+, and pSTAT6+ monocytes and pSTAT5+ lymphocytes than HDs. After 24weeks of treatment, percentages of IFNγ-induced pSTAT1+ and IL-10-induced pSTAT3+ monocytes in RA patients increased, reaching levels comparable to HDs. pSTAT1+ and pSTAT3+ cells correlated inversely with RA disease activity index and levels of pSTAT+ cells at baseline were higher in patients with good EULAR response to tocilizumab. IFNγ-induced pSTAT1+ cells correlated inversely with memory T cells and anti-CCP levels. IL-10-induced pSTAT3+ cells correlated with Treg/Teff ratio. Our findings suggest that IL-6 blocking reduces the inflammatory mechanisms through the correction of STAT1 and STAT3 activation status.

Integrated production of polyhydroxyalkanoates (PHAs) with municipal wastewater and sludge treatment at pilot scale.

A pilot-scale process was operated over 22 months at the Brussels North Wastewater Treatment Plant (WWTP) in order to evaluate polyhydroxyalkanoate (PHA) production integration with services of municipal wastewater and sludge management. Activated sludge was produced with PHA accumulation potential (PAP) by applying feast-famine selection while treating the readily biodegradable COD from influent wastewater (average removals of 70% COD, 60% CODsol, 24% nitrogen, and 46% phosphorus). The biomass PAP was evaluated to be in excess of 0.4gPHA/gVSS. Batch fermentation of full-scale WWTP sludge at selected temperatures (35, 42 and 55 °C) produced centrate (6-9.4 gCODVFA/L) of consistent VFA composition, with optimal fermentation performance at 42 °C. Centrate was used to accumulate PHA up to 0.39 gPHA/gVSS. The centrate nutrients are a challenge to the accumulation process but producing a biomass with 0.5 gPHA/gVSS is considered to be realistically achievable within the typically available carbon flows at municipal waste management facilities.

Therapeutic effect of an altered peptide ligand derived from heat-shock protein 60 by suppressing of inflammatory cytokines secretion in two animal models of rheumatoid arthritis.

Rheumatoid arthritis is a systemic autoimmune disease mediated by T cells. Productive engagement of T cell receptors by major histocompatibility complex-peptide leads to proliferation, differentiation and the definition of effector functions. Altered peptide ligands (APL) generated by amino acid substitutions in the antigenic peptide have diverse effects on T cell response. We predicted a novel T cell epitope from human heat-shock protein 60, an autoantigen involved in the pathogenesis of rheumatoid arthritis. Three APLs were designed from this epitope and it was demonstrated that these peptides induce the activation of T cells through their ability to modify cell cycle phase's distribution of CD4+T cells from RA patients. Also, IL-17, TNF-α and IL-10 levels were determined in PBMC from these patients. Unlike the wild-type peptide and the other two APLs, APL2 increased the IL-10 level and suppressed IL-17 secretion in these assays. Therapeutic effect of this APL in adjuvant arthritis (AA) and collagen-induced arthritis (CIA) models was also evaluated. Clinical score, histopathology, inflammatory and regulatory cytokine concentration were monitored in the animals. APL2 efficiently inhibited the progression of AA and CIA with a significant reduction of the clinical and histopathologic score. Therapeutic effect of APL2 on CIA was similar to that obtained with MTX; the standard treatment for RA. This effect was associated with a decrease of TNF-α and IL-17 levels. These results suggest that the therapeutic effect of APL2 is mediated in part by down-regulation of inflammatory cytokines and support the potential use of APL2 as a therapeutic drug in RA patients.

Efficacy of the Bm86 antigen against immature instars and adults of the dog tick Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae).

The Bm86 antigen has been used to control ticks of the Boophilus genera in integrated programs that also include the use of acaricides. Because of recent phylogenetic studies have lead to the inclusion of all Boophilus species within the Rhipicephalus genera, we aimed to investigate the efficacy of the Bm86 antigen on the biotic potential of Rhipicephalus sanguineus. Domestic dogs were vaccinated with Bm86 and challenged with the three instars of R. sanguineus. Male and female mongrel dogs were divided into two groups of four animals each, comprising non-vaccinated and vaccinated animals. Immunized dogs were given two doses of an experimental formulation containing 50mug of recombinant Bm86, at 21 days interval while the other group was given placebo, consisting of the same preparation without Bm86. Each dog was challenged 21 days after the last dose with 250 larvae, 100 nymphs and 55 adults (25 females and 30 males) released inside feeding chambers (one per instar) glued to their shaved flank. The effect of the vaccination was evaluated by determining biological parameters of ticks including the yield rates of larvae, nymphs and adult females. Adult females engorged weight, egg mass weight, efficiency rate of conversion to eggs (ERCE) and hatchability. In addition, sera were collected from dogs at 0, 21, 36, 45 and 75 days after the vaccination and used for the detection of specific antibodies by ELISA. Collection rates of larvae, nymphs and adult females fed on vaccinated dogs were significantly (p<0.05) reduced by 38%, 29% and 31%, respectively, as compared with non-vaccinated controls. Significant reductions were also observed in weight of engorged females and egg mass, in ERCE, but not in the hatch rate of ticks fed on immunized dogs. ELISA data revealed a marked and significant increase in optical densities of sera from vaccinated animals after the second dose of Bm86. We concluded that the Bm86 antigen used as a vaccine for dogs reduced the viability and biotic potential of the R. sanguineus.

Disability measured by the modified health assessment questionnaire in early rheumatoid arthritis: prognostic factors after two years of follow-up.

OBJECTIVE: To analyze the rate and baseline prognostic factors of disability measured by the modified HAQ (MHAQ), in a series of patients with early rheumatoid arthritis (RA) after two years of therapy with a structured algorithm using disease-modifying anti-rheumatic drugs (DMARDs). METHODS: One hundred and five patients (81% female) with early RA (disease duration <2 years) treated with the same therapeutic protocol using gold salts and methotrexate in a step-up strategy, together with methylprednisolone (4 mg/day), were followed up for two years. The outcome was the absence of disability (MHAQ=0) after two years of DMARD therapy. Clinical, biological, immunogenetic and radiographic data (Larsen score) were analyzed at study entry and at 12 and 24 months of follow-up. RESULTS: The MHAQ decreased significantly at 6 months after initiation of DMARD therapy and the reduction was maintained at 24 months (mean+/-SD: 0.97+/-0.56 at baseline, 0.51+/- 0.57 at month 6 and 0.45+/-0.5 at month 24). No disability (MHAQ=0) was observed in 26.6% of patients after two years of follow-up. Age, MHAQ>0.5, DAS28>5.1, VAS pain, positive rheumatoid factor and ESR at baseline were associated with disability in the univariate analysis. In the logistic regression analysis, only age (OR: 1.058, 95%CI 1.017; 1.101 p<0.006), rheumatoid factor status (OR: 3.772 95%CI 1.204; 11.813, p<0.02) and MHAQ>0.5 (OR:4.023, 95%CI 1.373; 11.783, p<0.02) were associated with disability (MHAQ>0) at two years. CONCLUSION: In a series of early RA patients treated with a structured algorithm using DMARDs and very low doses of glucocorticoids, no disability was observed in a quarter of patients after two years. Age, rheumatoid factor positivity and MHAQ>0.5 were independent predictors of disability at two years.

Influence of variants of Fc gamma receptors IIA and IIIA on the American College of Rheumatology and European League Against Rheumatism responses to anti-tumour necrosis factor alpha therapy in rheumatoid arthritis.

OBJECTIVE: Fc gamma receptor (Fc gammaR) polymorphism influences the affinity of the receptor for Ig, which may, in turn, affect the efficacy of Ig-based therapies. The relationship between functional single nucleotide polymorphisms (SNP) of the FCGR2A and FCGR3A genes and the response to anti-tumour necrosis factor (TNF)alpha therapy (infliximab) in patients with rheumatoid arthritis (RA) was assessed. METHODS: A total of 91 patients with RA (89% female; 76.7% rheumatoid factor (RF) positive) starting therapy with infliximab were evaluated at 0, 6 and 30 weeks using the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria and the 28-joint Disease Activity Score (DAS28) was evaluated using three parameters, including C-reactive protein (CRP) (DAS28 3v-CRP) changes during the follow-up. Genotyping of FCGR2A-R131H and FCGR3A-F158V polymorphisms was performed by allele-specific PCR and PCR sequence-based typing, respectively. The chi(2) and Fisher exact tests were used to show differences in the outcome variables, and analysis of variance (ANOVA) to analyse the evolution of DAS28 3v-CRP. A generalised linear models multivariable analysis was also performed. RESULTS: At week 6 of follow-up, the proportion of patients achieving 50% improvement as per ACR criteria (ACR50) and EULAR good responses were significantly higher among homozygotes of the low affinity FCGR3A allele (FF: 24.1% and VV-VF:2.2%; p = 0.003 and FF: 44.8% and VV-VF: 22.9%; p = 0.040, respectively). At week 30, homozygotes of the low affinity FCGR2A allele had a better ACR20 response (RR: 60% and HH-RH: 33.3%; p = 0.035). Changes in DAS28 3v-CRP during follow-up were consistent with those observed in ACR and EULAR responses. CONCLUSIONS: The response to anti-TNFalpha treatment with infliximab in patients with RA is influenced by the FCGR2A and FCGR3A genotypes. This effect is observed at different times in the follow-up (6 and 30 weeks, respectively) indicating the dynamic nature of the Fc gammaR versus Ig interaction.

Non-typhi Salmonella infection in patients with rheumatic diseases on TNF-alpha antagonist therapy.

OBJECTIVES: The morbidity and mortality of patients with rheumatic diseases has improved considerably following the use of biologic therapies. However, an increase in the frequency of bacterial infections has been observed in patients receiving these drugs. In the present study we aimed to establish the incidence and clinical manifestations of non-typhi Salmonella infection in a large cohort of patients with rheumatic diseases undergoing TNF-alpha antagonist therapy due to severe rheumatic diseases refractory to conventional therapies. METHODS: The rate of non-typhi Salmonella infection found in the Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases (BIOBADASER) was compared with that observed in a cohort of rheumatoid arthritis (RA) patients from the EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) Study, who were not treated with TNF-alpha antagonists. The rate found in the BIOBADASER registry was also compared with that available in a non-RA historic control cohort reported in a population from Huesca (Northern Spain). RESULTS: Seventeen cases of non-typhi Salmonella infection were observed in the series of patients exposed to anti-TNF-alpha therapies. The incidence rate of non-typhi Salmonella in BIOBADASER was 0.73 per 1000 patient-years (95% confidence interval [CI]: 0.45-1.17). The incidence rate in the EMECAR cohort was 0.44 per 1000 patient-years. The relative risk for non-typhi salmonellosis in RA patients exposed to TNF-alpha inhibitors compared to those not treated with biological therapies was 2.07 (95% CI: 0.27-15.73) (p=0.480) whereas the relative risk of non-typhi Salmonella infections in patients with rheumatic diseases undergoing TNF-alpha antagonist therapy compared with the non-RA Spanish control cohort was 0.63 (95% CI: 0.38-1.04) (p=0.07). Nine of the 17 patients with non-typhi salmonellosis presented a severe systemic infection. CONCLUSION: Incidence of non-typhi Salmonella infection is not increased significantly in rheumatic patients undergoing anti-TNF-alpha therapy when compared with RA patients undergoing conventional DMARD therapy or with the general population. Nevertheless, at least 50% of patients on TNF-alpha have severe complications once they develop non-typhi Salmonella infection. This fact suggests that anti-TNF-alpha therapies may predispose to salmonella dissemination rather than to infection.