Ultrasound Doppler enthesitis shows sensitivity to change after biological therapy in spondyloarthritis and psoriatic arthritis patients.

OBJECTIVE: To explore the sensitivity to change in power Doppler (PD) enthesitis in active spondyloarthritis (SpA) and psoriatic arthritis (PsA) patients. METHOD: This was a longitudinal study in patients with SpA and PsA with active disease [patients starting or switching to biological disease-modifying anti-rheumatic drugs (bDMARDs)]. The MAdrid Sonographic Enthesitis Index (MASEI) was performed at baseline and at 3 and 6 month visits. The MASEI and Outcome Measures in Rheumatology (OMERACT) PD enthesitis definitions were checked. Reliability analysis among three readers was performed with ultrasound (US)-recorded videos. RESULTS: US examinations of 25 patients were included; 16 (64%) had SpA and nine (36%) PsA. The median (interquartile range, IQR) age was 49 (41-61) years, and 13 patients (52%) were female. The median (IQR) 28-joint Disease Activity Score of 3.6 (2.3-4.2), Bath Ankylosing Spondylitis Disease Activity Index of 6.7 (6.1-7.4), and C-reactive protein value of 8.2 (1.6-20) reflected moderate to high disease activity at baseline. Both MASEI and OMERACT PD enthesitis improved significantly at 3 and 6 month follow-up (p < 0.05) and showed sensitivity to change (standard error of measurement = 0.47 and 0.61, respectively). Improvement in clinical activity outcomes was significantly associated with decreases in MASEI and OMERACT PD enthesitis counts (p < 0.05). The MASEI and OMERACT PD definitions had excellent reliability (kappa = 0.918 and 0.865, respectively). CONCLUSION: PD enthesitis significantly improved at 3 and 6 month follow-up in patients undergoing bDMARD therapy. Both MASEI and OMERACT PD US enthesitis reflect response to treatment.

Effect of tranexamic acid administration on bleeding in primary total hip arthroplasty. / Efecto de dosis única intravenosa de ácido tranexámico sobre el sangrado en artroplastia total de cadera. Estudio prospectivo, controlado y aleatorizado.

OBJECTIVE: To study the efficacy of tranexamic acid to decrease perioperative bleeding in patients who have undergone a total hip arthroplasty operation and to evaluate drug safety. MATERIAL AND METHODS: Observational, prospective, controlled and randomized study on the efficacy of tranexamic acid as a method to reduce bleeding in primary hip replacement surgery. We included 134 patients operated during 2014 in our centre, who were divided into 2 groups according to whether or not they had received tranexamic acid. The main study variables were haemoglobin and haematocrit levels, the amount of blood collected from the post-operative drain in the first 12, 24 and 48hours and transfusion requirements. RESULTS: Post-operative haemoglobin and haematocrit levels were statistically higher (P<.001) in the group with treatment. During the first 48hours bleeding values from the group that did not receive TAX were higher compared to patients treated with tranexamic acid. Statistically significant differences (P=.001) were found as to the need for transfusion according to group, more transfusions were performed in the cohort that had not received tranexamic acid: 25.37% compared to 4.48% for the group with tranexamic acid. No adverse events related to administration of tranexamic acid were recorded. CONCLUSIONS: Administration of tranexamic acid has proved to be an effective and safe method to reduce peri-operative bleeding in patients who underwent total hip arthroplasty and avoids allogenic blood transfusion. Therefore, tranexamic acid treatment could entail a financial saving for the healthcare system and expose the patient to less risk.

Manifestaciones radiológicas del síndrome de Baastrup en la edad pediátrica / Radiological manifestations of Baastrup's disease in children

Entre las causas de dolor lumbar en el niño no suele considerarse, como posibilidad diagnóstica, el síndrome de Baastrup. Clásicamente, esta entidad se caracteriza por fenómenos degenerativos secundarios al roce de apófisis espinosas adyacentes, con esclerosis de sus márgenes y disminución del espacio interespinoso. Su frecuencia aumenta con la edad y suele acompañarse de cambios degenerativos en el raquis, como pueden ser la hipertrofia facetaria lumbar o la patología discal. Determinadas actividades, como la danza o la gimnasia, pueden favorecer la aparición de esta patología a edades más tempranas. En la población infantil la enfermedad pudiera manifestarse de modo diferente, con aumento del espacio interespinoso y remodelación ósea(AU)

Baastrup's disease is not usually considered among the possible causes of low back pain in children. Classically, Baastrup's disease is characterized by degenerative phenomena secondary to friction between adjacent spinous processes, with sclerosis of the margins and decrease in the interspinous space. Baastrup's disease becomes more prevalent with age and is usually accompanied by degenerative changes in the vertebral column, such as lumbar facet hypertrophy or disc disease. Certain activities like dance or gymnastics can make Baastrup's disease more likely to appear at an earlier age. In children, Baastrup's disease can manifest in a different way, with increased interspinous spaces and bone remodeling. In this article, we present the cases of two patients with low back pain who were diagnosed with Baastrup's disease(AU)

[Radiological manifestations of Baastrup's disease in children]. / Manifestaciones radiológicas del síndrome de Baastrup en la edad pediátrica.

Baastrup's disease is not usually considered among the possible causes of low back pain in children. Classically, Baastrup's disease is characterized by degenerative phenomena secondary to friction between adjacent spinous processes, with sclerosis of the margins and decrease in the interspinous space. Baastrup's disease becomes more prevalent with age and is usually accompanied by degenerative changes in the vertebral column, such as lumbar facet hypertrophy or disc disease. Certain activities like dance or gymnastics can make Baastrup's disease more likely to appear at an earlier age. In children, Baastrup's disease can manifest in a different way, with increased interspinous spaces and bone remodeling. In this article, we present the cases of two patients with low back pain who were diagnosed with Baastrup's disease.

Synthesis and characterization of PbSe nanoparticles obtained by a colloidal route using Extran as a surfactant at low temperature.

Lead selenide nanoparticles (PbSe NPs) have been obtained through an easy and low cost route using colloidal synthesis in aqueous solution. The synthesis was carried out at room temperature using Extran (Na5P3O10, NaOH and H2O) as surfactant. Hydrochloric acid (HCl) was used to eliminate the generated by-products. The size of PbSe NPs was varied by changing the Pb:Se molar concentration. The PbSe NPs were characterized by powder x-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive x-ray analysis (EDAX), high-resolution transmission electron microscopy (HRTEM) and Raman spectroscopy. The XRD measurements showed that the PbSe NPs have the face-centered cubic phase structure. The crystal size was found to be between 14 and 20 nm as calculated from the XRD patterns and these values were corroborated with SEM and TEM. Additionally, HRTEM micrographs showed crystalline planes at (200), (220) and (111) of the PbSe NPs, in agreement with the XRD results.

Aggressive transformation of a quiescent primary bone lymphoma simulating Paget's disease.

Primary multifocal osseous lymphoma is a rare and poorly recognized entity. Here, we present an instructive case of a young man who, six years after a local contusion of the left ankle, developed a painful polylobulated large soft tissue mass. This mass turned out to have arisen from the transformation of a centro follicular non-Hodgkin's lymphoma into a diffuse large B-cell lymphoma involving the calcaneus, talus, cuboid and navicular bones. The diagnostic difficulties as well as the implications of this aggressive transformation are highlighted here.

[Scrotal ultrasound: pearls, patterns and pitfalls]. / Ecografía escrotal: perlas, patrones y errores.

We present a review of the scrotal ultrasound findings showing normal anatomic variants that may simulate scrotal pathology (rete testis dilatation, normal testicle and epididymis appendages). US patterns of the scrotal pathology may be classified as: calcified (scrotal and albuginea calcifications, microcalcifications, epididymis calcifications, testicular tumors with calcium), cystic appereance (intratesticular and echogenic varicocele, epididymis cysts, albuginea cysts, haematoma, abscess), solid nodular testicular lesions (infarct, neoplasm) and diffuse lesions (orchitis, lymphoid hyperplasia lymphoma, leukemia). Testicular ultrasound may be helpful in detecting extraescrotal pathologies. There is a known relationship between right varicocele and extratesticular neoplasms. We also show some cases of Burn-out testicular tumor and their MR, CT and PET findings. The knowledge of normal US scrotal anatomy, US patterns of the scrotal lesions and scrotal findings that suggest extratesticular pathologies are crucial in the management of testicular pathology and if unnecessary orchiectomies want to be avoided.

Ecografía escrotal: perlas, patrones y errores / Scrotal ultrasound: pearls, patterns and pitfalls

En este trabajo presentamos una revisión de los hallazgos de la ecografía escrotal mostrando variantes anatómicas escrotales (dilatación de la rete testis, apéndices testiculares y epididimarios) que simulan enfermedad. Revisamos la patología escrotal agrupada semiológicamente incluyendo lesiones con calcio (escrotolitos, calcificación de la albugínea, microlitiasis testicular, calcificaciones epididimarias, neoplasias testiculares con calcificaciones), lesiones con contenido líquido (quistes de epidídimo, de la albugínea, testiculares, varicocele intratesticular, abscesos y hematomas testiculares, varicocele extratesticular con contenido ecogénico), lesiones nodulares sólidas de testículo (infartos y neoplasias) y lesiones difusas del testículo (linfoma, leucemia, hiperplasia linfoide, orquitis). Otra de las utilidades de la ecografía escrotal es considerar determinados hallazgos escrotales como marcadores de patología extraescrotal. Mostramos la asociación de neoplasias extraescrotales con varicocele derecho y varios casos de “Burn-out tumor” con neoplasia testicular “in situ” y sus hallazgos de RM, TC y PET. Se concluye que el conocimiento de la anatomía normal ecográfica, de los diferentes patrones de presentación de las lesiones y de los hallazgos escrotales que indican patología extratesticular ayudan en el manejo de los pacientes y pueden evitar cirugías innecesarias

We present a review of the scrotal ultrasound findings showing normal anatomic variants that may simulate scrotal pathology (rete testis dilatation, normal testicle and epididymis appendages). US patterns of the scrotal pathology may be classified as: calcified (scrotal and albuginea calcifications, microcalcifications, epididymis calcifications, testicular tumors with calcium), cystic appereance (intratesticular and echogenic varicocele, epididymis cysts, albuginea cysts, haematoma, abscess), solid nodular testicular lesions (infarct, neoplasm) and diffuse lesions (orchitis, lymphoid hyperplasia lymphoma, leukemia). Testicular ultrasound may be helpful in detecting extraescrotal pathologies. There is a known relationship between right varicocele and extratesticular neoplasms. We also show some cases of Burn-out testicular tumor and their MR, CT and PET findings. The knowledge of normal US scrotal anatomy, US patterns of the scrotal lesions and scrotal findings that suggest extratesticular pathologies are crucial in the management of testicular pathology and if unnecessary orchiectomies want to be avoided

Respuesta del panel de expertos / Experts board's reply

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Licofelone--clinical update on a novel LOX/COX inhibitor for the treatment of osteoarthritis.

Licofelone, a competitive inhibitor of 5-lipoxygenase, cyclooxygenase (COX)-1 and COX-2, is currently in clinical development for the treatment of osteoarthritis (OA). Licofelone decreases the production of proinflammatory leukotrienes and prostaglandins-which are involved in the pathophysiology of OA and in gastrointestinal (GI) damage induced by NSAIDs-and has the potential to combine good analgesic and anti-inflammatory effects with excellent GI tolerability. Initial endoscopy data in healthy volunteers have demonstrated that licofelone is well tolerated and has a GI safety profile similar to placebo and significantly better than naproxen. These tolerability results were confirmed in patients with OA in two separate randomized studies. Furthermore, a long-term study (52 weeks) has shown that licofelone is at least as effective as naproxen in the treatment of OA. Licofelone also appears to be as effective as the selective COX-2 inhibitor celecoxib in the treatment of the signs and symptoms of OA. Licofelone has a GI safety profile similar to that of celecoxib, but may offer the advantage of fewer incidences or worsening of peripheral oedema. Preliminary data have also shown that licofelone coadministration with low-dose aspirin does not lead to increased GI toxicity. The emerging clinical data for licofelone indicate that it is an effective and well-tolerated therapy that could offer safety advantages over current treatment options, and that it could be suitable for the long-term treatment of a broad spectrum of patients with OA.

Papanicolaou smears of atypical glandular cells of undetermined significance: histological correlations and suggestions for management.

OBJECTIVE: We sought to correlate cervical and endometrial neoplasias with Papanicolaou (Pap) smears of atypical glandular cells of undetermined significance (AGUS) and to suggest management. MATERIALS AND METHODS: One hundred seventy-one patients with AGUS Pap smears were followed prospectively with colposcopy, biopsies, endocervical curettage, and endometrial biopsies. RESULTS: One hundred twelve patients (65%) with AGUS Pap smears favoring reactive changes were found to harbor 13 preinvasive and invasive cervical squamous neoplasias and 1 ovarian sarcoma (total, 12.5% of patients with smears). Fifty-nine patients (35%) with AGUS Pap smears favoring neoplastic changes harbored 25 preinvasive and invasive squamous and glandular cervical and endometrial neoplasias (42.3%). CONCLUSION: In the presence of an AGUS Pap smear favoring reactive changes, colposcopy, biopsies, and endocervical curettage should be performed. Endometrial biopsy should be added when AGUS Pap smear favors neoplasia.

Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist.

OBJECTIVE: To evaluate the efficacy and safety of interleukin-1 receptor antagonist (IL-1Ra) in patients with rheumatoid arthritis (RA). METHODS: Patients with active and severe RA (disease duration <8 years) were recruited into a 24-week, double-blind, randomized, placebo-controlled, multicenter study. Doses of nonsteroidal antiinflammatory drugs and/or oral corticosteroids (< or =10 mg prednisolone daily) remained constant throughout the study. Any disease-modifying antirheumatic drugs that were being administered were discontinued at least 6 weeks prior to enrollment. Patients were randomized to 1 of 4 treatment groups: placebo or a single, self-administered subcutaneous injection of IL-1Ra at a daily dose of 30 mg, 75 mg, or 150 mg. RESULTS: A total of 472 patients were recruited. At enrollment, the mean age, sex ratio, disease duration, and percentage of patients with rheumatoid factor and erosions were similar in the 4 treatment groups. The clinical parameters of disease activity were similar in each treatment group and were consistent with active and severe RA. At 24 weeks, of the patients who received 150 mg/day IL-1Ra, 43% met the American College of Rheumatology criteria for response (the primary efficacy measure), 44% met the Paulus criteria, and statistically significant improvements were seen in the number of swollen joints, number of tender joints, investigator's assessment of disease activity, patient's assessment of disease activity, pain score on a visual analog scale, duration of morning stiffness, Health Assessment Questionnaire score, C-reactive protein level, and erythrocyte sedimentation rate. In addition, the rate of radiologic progression in the patients receiving IL-1Ra was significantly less than in the placebo group at 24 weeks, as evidenced by the Larsen score and the erosive joint count. IL-1Ra was well tolerated and no serious adverse events were observed. An injection-site reaction was the most frequently observed adverse event, and this resulted in a 5% rate of withdrawal from the study among those receiving IL-1Ra at 150 mg/day. CONCLUSION: This study confirmed both the efficacy and the safety of IL-1Ra in a large cohort of patients with active and severe RA. IL-1Ra is the first biologic agent to demonstrate a beneficial effect on the rate of joint erosion.

Transient osteoporosis of the hip: successful response to deflazacort.

Transient osteoporosis of the hip (TOH) is an uncommon condition with a poorly defined aetiology. Despite its benign prognosis, its long clinical course causes a prolonged period of functional disability in middle-aged patients. We describe two patients with TOH who showed a rapid response to deflazacort, a bone-sparing corticoid. Deflazacort may become a useful tool to shorten the otherwise lengthy recovery period of TOH.

[A randomized study of navelbine compared to navelbine and cisplatin compared to vindesine and cisplatin in the treatment of inoperable non-small-cell lung carcinoma. The results of a European multicenter study including 612 patients]. / Estudio con reparto aleatorio de navelbina frente a navelbina y cisplatino frente a vindesina y cisplatino en el tratamiento del carcinoma pulmonar no microcelular inoperable. Resultados de un estudio multicéntrico europeo incluyendo 612 pacientes.

The results are reported of three chemotherapy schedules in a multicentric, international, randomized trial of the therapy of unresectable non small cell lung carcinoma which included 612 patients. The antitumoral efficiency of the cisplatin + vindesine combination (200 patients) was compared with that of navelbine (206 patients), a recently available vinca alkaloid, and with a third therapeutical leg with cisplatin + navelbine (206 patients). After a very thorough response evaluation the combination cisplatin + navelbine obtained a response rate higher than the other combination (30% vs. 19%; p = 0.02) and also than navelbine (30% vs. 14%; p < 0.001). The median response durations were 9.3, 9.9, and 7.8 months for the combination with navelbine, vindesine and the new vinca alkaloid alone, respectively. After a median follow-up period of 26 months the combination cisplatin + navelbine achieved a higher survival rate than the combination cisplatin + vindesine (40 vs. 32 weeks) and navelbine (40 vs 31 weeks; p = 0.045). The most important toxicity with the combination cisplatin + navelbine was neutropenia, which although relevant in number was not of long duration. In summary, navelbine is an active agent in the therapy of non small cell lung carcinoma. In this trial the therapeutic superiority of its combination with cisplatin over the combination cisplatin + vindesine was observed; likewise, it was also more efficient than monotherapy with navelbine.

Mutual antagonism between interferon-gamma and tumor necrosis factor-alpha on fibroblast-like synoviocytes: paradoxical induction of IFN-gamma and TNF-alpha receptor expression.

We recently described mutual antagonism between IFN-gamma and TNF-alpha on human fibroblast-like synoviocytes (FLS). TNF-alpha inhibits IFN-gamma-induced HLA-DR expression and IFN-gamma blocks TNF-alpha-dependent synoviocyte proliferation, collagenase production, and GM-CSF secretion. To study the mechanism of antagonism we have analyzed the effect these factors on the expression of cytokine surface receptors. 125I-Labeled cytokine binding was measured on cultured FLS and the results were analyzed by Scatchard plots. Unstimulated synoviocytes expressed 9300 +/- 1560 IFN-gamma binding sites per cell. A single class of high-affinity receptor was observed (Kd = 4.5 +/- 2.5 x 10(-10) M). TNF-alpha did not competitively inhibit 125I-IFN-gamma binding. When FLS were incubated with TNF-alpha (100 ng/ml), there was a paradoxical 49.5 +/- 5.6% increase in the number of binding sites for IFN-gamma (P = 0.001), with no change in the Kd. Unstimulated FLS also expressed 2850 +/- 700 TNF-alpha receptors per cells, with a single Kd consistent with the lower-affinity TNF-alpha receptor (7.4 +/- 0.2 x 10(-10) M). IFN-gamma did not directly interfere with TNF-alpha binding. Preincubation of FLS with 100 U/ml of IFN-gamma resulted in a 28.9 +/- 9.0% increase in TNF-alpha receptor expression (P < 0.008), with no change in the Kd. Low levels of the soluble 55-kD TNF receptor were detected in FLS supernatants. IFN-gamma did not effect soluble TNF receptor production.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha 4/beta 1 integrin (VLA-4) ligands in arthritis. Vascular cell adhesion molecule-1 expression in synovium and on fibroblast-like synoviocytes.

Expression of vascular cell adhesion molecule-1 (VCAM-1) in synovial tissue was determined using the immunoperoxidase technique. Normal, rheumatoid arthritis (RA), and osteoarthritis (OA) synovia bound VCAM-1 antibodies in the intimal lining as well as blood vessels. The amount of VCAM-1 was significantly greater in the synovial lining of RA and OA tissues compared with normal synovium (p less than 0.002). There was also a trend toward greater levels of VCAM-1 staining in blood vessels of arthritic tissue (RA greater than OA greater than normal). Because VCAM-1 staining was especially intense in the synovial lining, VCAM-1 expression and regulation was studied on cultured fibroblast-like synoviocytes (FLS) derived from this region. Both VCAM-1 and intercellular adhesion molecule 1 were constitutively expressed on FLS. VCAM-1 expression was further increased by exposure to IL-1 beta, TNF-alpha, IL-4, and IFN-gamma. These cytokines (except for IL-4) also induced intercellular adhesion molecule 1 expression on FLS. ELAM was not detected on resting or cytokine-stimulated FLS. The specificity of VCAM-1 for FLS was demonstrated by the fact that only trace amounts were detected on normal and RA dermal fibroblasts. Cytokines induced intercellular adhesion molecule 1 display on dermal fibroblasts but had minimal effect on VCAM-1 expression. Finally, in adherence assays, Jurkat cell binding to resting FLS monolayers was inhibited by antibody to alpha 4/beta 1 integrin (VLA-4), CS-1 peptide from alternatively spliced fibronectin (which is another VLA-4 ligand), and, to a lesser extent, anti-VCAM-1 antibody. After cytokine stimulation of FLS, Jurkat-binding significantly increased, and this increase was blocked by anti-VCAM-1 antibody. Therefore, both CS-1 and VCAM-1 participate in VLA-4-mediated adherence to resting FLS in vitro, and VCAM-1 is responsible for the increase in Jurkat binding mediated by cytokines.