Capi-score: a quantitative algorithm for identifying disease patterns in nailfold videocapillaroscopy.

OBJECTIVES: The European Alliance of Associations for Rheumatology (EULAR) supports the use of nailfold videocapillaroscopy (NVC) to identify disease patterns (DPs) associated with systemic sclerosis (SSc) and Raynaud's phenomenon (RP). Recently, EULAR proposed an easy-to-manage procedure, a so-called Fast Track algorithm, to differentiate SSc from non-SSc patterns in NVC specimens. However, subjectivity among capillaroscopists remains a limitation. Our aim was to perform a software-based analysis of NVC peculiarities in a cohort of samples from SSc and RP patients and, subsequently, build a Fast Track-inspired algorithm to identify DPs without the constraint of interobserver variability. METHODS: NVCs were examined by 9 capillaroscopists. Those NVCs whose DPs were consensually agreed (≥2 out of 3 interobservers) were subsequently analysed with an in-house developed software. Each variable's results were grouped according to the consensually agreed DPs in order to identify useful hallmarks to categorise them. RESULTS: Eight-hundred and fifty-one NVCs (21 957 images) whose DPs had been consensually agreed were software-analysed. Appropriate cut-offs set in capillary density and percentage of abnormal and giant capillaries, tortuosities and hemorrhages allowed DP categorization and the development of the CAPI-Score algorithm. This consisted of 4 rules: Rule 1, SSc vs non-SSc, accuracy 0.88; Rules 2 and 3, SSc-early vs SSc-active vs SSc-late, accuracy 0.82; Rule 4, non-SSc normal vs non-SSc non-specific, accuracy 0.73. Accuracy improved when the analysis was limited to NVCs whose DPs had achieved full consensus among interobservers. CONCLUSIONS: The CAPI-Score algorithm may become a useful tool to assign DPs by overcoming the limitations of subjectivity.

Stability of anterior open bite treatment with bonded spurs associated with high-pull chincup.

OBJECTIVE: To evaluate the stability of anterior open bite (AOB) treatment with bonded spurs associated with high-pull chincup (BS/HPCC). METHODS: The experimental group consisted of 25 Class I AOB patients (15 female, 10 male) treated with BS/HPCC for 1 year. Cephalograms were analysed at pre-treatment (T1), post-treatment (T2) and at the 3-year post-treatment (T3) stage with the patients mean ages of 8.10, 9.14 and 12.18 years, respectively. The control group consisted of 23 subjects (13 female, 10 male) with normal occlusion, with comparable ages at the 3 stages (8.45, 9.45 and 12.50 years at T1, T2 and T3, respectively). T tests were used for intergroup comparisons at T1 and to compare the changes during the 3-year post-treatment period (T2-T3). Intragroup comparison in the treated group was evaluated with dependent t tests between T1 and T2. Correlations between the overbite changes in the T2-T3 period, the pre-treatment AOB severity and the amount of correction achieved during treatment were evaluated with Pearson's correlation coefficient. RESULTS: No statistically significant relapse of the AOB was found at T3. Only 1 patient had a clinically significant AOB relapse. Neither the pre-treatment AOB severity nor the amount of correction was related to overbite changes during the 3-year post-treatment period. CONCLUSIONS: There was no statistically significant relapse of the AOB, and the clinical stability of AOB correction 3-year post-treatment was of 96%.

Diagnosis and quantification of fibrosis, steatosis, and hepatic siderosis through multiparametric magnetic resonance imaging. / Diagnóstico y cuantificación de fibrosis, esteatosis y hepatosiderosis por medio de resonancia magnética multiparamétrica.

BACKGROUND: The presence of liver fibrosis is the common denominator in numerous chronic liver diseases that can progress to fibrosis and hepatocellular carcinoma. Most important, with respect to frequency, are viral hepatitis and non-alcoholic fatty liver disease, the prevalence of which is increasing in epidemic proportions. Liver biopsy, albeit imperfect, continues to be the criterion standard, but in many clinical situations tends to be replaced with noninvasive imaging methods. OBJECTIVES: The aim of the present article was to describe our imaging department experience with magnetic resonance elastography and to analyze and discuss recently published results in gastroenterology, hepatology, and radiology from other authors in the literature, complemented with a PubMed search covering the last 10 years. RESULTS AND CONCLUSIONS: Magnetic resonance elastography is an efficacious, noninvasive method with results that are concordant with liver biopsy. It is superior to ultrasound elastography because it evaluates a much greater volume of hepatic tissue and shows the often heterogeneous lesion distribution. The greatest advantage of the magnetic resonance protocol described is the fact that it quantifies fibrosis, fat content, and iron content in the same 25min examination specifically directed for that purpose, resulting in a favorable cost-benefit ratio for the patient and/or institution.

Increased myo-inositol in parietal white and gray matter as a biomarker of poor prognosis in neuropsychiatric lupus: a case report.

Neuropsychiatric manifestations can be a serious complication of systemic lupus erythematosus, affecting nearly 56% of these patients. Frequently, acceptable clinical outcome is observed in neurolupus with immunosuppressive therapy. Different metabolites identified with MR spectroscopy may be associated with modifications in the natural history of this disease, specifically in the central nervous system. We report a case of neurolupus with progressive neurologic impairment despite aggressive immunosuppressive treatment. We describe clinical features, laboratory and MRI results, as well as characteristic findings on MR spectroscopy. Serial MRI identified atrophy of the left temporal lobe. MR spectroscopy showed an increase of myo-inositol/creatine ratio intensity, accompanied by a decrease of N-acetylaspartate/creatine ratio in both parietal white and gray matter. During follow-up, the patient developed progressive cognitive deficiency despite the intensification of therapy. Neurolupus manifestations are common and immunosuppressive treatment often avoids severe complications. Characteristic findings on MR spectroscopy may be useful for clinicians to determine poor prognosis and resistance to therapy.

Systemic sclerosis sine scleroderma and limited cutaneous systemic sclerosis: similarities and differences.

OBJECTIVES: To compare a cohort of patients with systemic sclerosis sine scleroderma (ssSSc) vs. patients with limited cutaneous systemic sclerosis (lcSSc). METHODS: Forty-five patients with ssSSc and 186 patients with lcSSc were investigated. Demographic, clinical and immunologic features and survival were compared. RESULTS: There were no significant differences between ssSSc and lcSSc in gender, age at onset and interval between onset and diagnosis. ssSSc patients fulfilled the ACR criteria for SSc less than lcSSc patients (13%/77%, p<0.0001). There were no significant differences in articular involvement, myopathy, tendon friction rubs and gastrointestinal, pulmonary, cardiac and renal involvements. There was a trend to higher prevalence of pulmonary arterial hypertension (PAH) in ssSSc patients (29%/19%) but not reach significant difference. The prevalence of antinuclear and anticentromere antibodies and slow capilaroscopic pattern was similar. Sicca syndrome (13%/30%; p=0.024), digital ulcers (16%/50%; p<0.0001), calcinosis (11%/26%; p=0.047) and acroosteolysis (0% /10%; p=0.028) were more frequently in lcSSc. Survival at 5, 10, and 15 yr was not different in ssSSc and lcSSc patients (100%/98%, 100%/98%, and 92%/89%, respectively). CONCLUSIONS: ssSSc and lcSSc patients share demographic, clinical and immunologic features. Survival is also similar in both groups. Differences are mainly due to peripheral vascular manifestations. However, despite great similarities, we believe that ssSSc patients should be considered as a different subset in order to avoid misdiagnosis. ssSSc patients should be truly differentiated from early SSc using sensitive and specific studies looking for any asymptomatic organ involvement.

Tailoring treatment for ductal intraepithelial neoplasia of the breast according to Ki-67 and molecular phenotype.

BACKGROUND: The post-surgical management of ductal intraepithelial neoplasia (DIN) of the breast is still a dilemma. Ki-67 labelling index (LI) has been proposed as an independent predictive and prognostic factor in early breast cancer. METHODS: The prognostic and predictive roles of Ki-67 LI were evaluated with a multivariable Cox regression model in a cohort of 1171 consecutive patients operated for DIN in a single institution from 1997 to 2007. RESULTS: Radiotherapy (RT) was protective in subjects with DIN with Ki-67 LI ≥ 14%, whereas no evidence of benefit was seen for Ki-67 LI <14%, irrespective of nuclear grade and presence of necrosis. Notably, the higher the Ki-67 LI, the stronger the effect of RT (P-interaction <0.01). Hormonal therapy (HT) was effective in both Luminal A (adjusted hazard ratio (HR)=0.56 (95% CI, 0.33-0.97)) and Luminal B/Her2neg DIN (HR 0.51 (95% CI, 0.27-0.95)). CONCLUSION: Our data suggest that Ki-67 LI may be a useful prognostic and predictive adjunct in DIN patients. The Ki-67 LI of 14% could be a potential cutoff for better categorising this population of women at increased risk for breast cancer and in which adjuvant treatment (RT, HT) should be differently addressed, independent of histological grade and presence of necrosis.

Systemic sclerosis associated myopathy: how to treat.

Purpose of review: Systemic sclerosis (SSc) and myositis are two different entities that may coexist as an overlap syndrome. Immunological biomarkers such as anti-PM/Scl or anti-Ku reinforce the syndrome. This review is focused on the treatment of different and characteristic manifestations of this syndrome. Recent findings: Among the different phenotypes of muscle involvement in patients with SSc, the fibrotic pattern and the sporadic inclusion body myositis must be identified early to avoid a futile immunosuppressive treatment. Other forms such as dermatomyositis, non-specific myositis and immune-mediated necrotizing myopathy need to receive conventional immunosuppressive therapy considering that high dose of glucocorticoids may induce a scleroderma renal crisis in patients with SSc. Physicians must be aware of the existence of a "double trouble" association of hereditary myopathy with an autoimmune phenomenon. Several autoantibodies, mainly anti-PM/Scl and anti-Ku may help to define specific phenotypes with characteristic clinical manifestations that need a more specific therapy. Vasculopathy is one of the underlying mechanisms that link SSc and myositis. Recent advances in this topic are reviewed. Summary: Current treatment of SSc associated myopathy must be tailored to specific organs involved. Identifying the specific clinical, pathological, and immunological phenotypes may help to take the correct therapeutic decisions.

Immunoglobulins in systemic sclerosis management. A large multicenter experience.

OBJECTIVE: To analyze the effectiveness and safety of intravenous immunoglobulin (IVIG) given in routine care to patients with systemic sclerosis (SSc). METHODS: A retrospective multicenter observational study was conducted in SSc patients treated with IVIG. We collected data on epidemiological parameters and clinical outcomes. Firstly, we assessed changes in organ manifestations during IVIG treatment. Secondly, we analyzed the frequency of adverse effects. The following parameters were collected from baseline to the last follow-up: the patient's weight, modified Rodnan Skin Score (mRSS), modified manual muscle strength scale (MRC), laboratory test(creatine kinase(CK), hemoglobin and protein levels), The University of California Los Angeles Scleroderma Clinical Trials Consortium gastrointestinal tract 2.0 (UCLA GIT 2.0) questionnaire, pulmonary function tests, and echocardiography. RESULTS: Data were collected on 78 patients (82% females; 59% with diffuse SSc). Inflammatory idiopathic myopathy was the most frequent concomitant overlap disease (41%). The time since Raynaud's phenomenon and SSc onset were 8.8 ± 18 and 6.2 ± 6.7 years respectively. The most frequent IVIG indication was myositis (38/78), followed by gastrointestinal (27/78) and cutaneous (17/78) involvement. The median number of cycles given were 5. 54, 53 and 9 patients have been treated previously with glucocorticoids, synthetic disease-modifying antirheumatic drugs and biologic therapies respectively. After IVIG use we found significant improvements in muscular involvement (MRC ≥ 3/5 92% IVIG, p = 0.001 and CK levels from 1149 ± 2026 UI to 217 ± 224 UI, p = 0.02), mRSS (15 ± 12.4 to 13 ± 12.5, p = 0.015) and improvement in total score of UCLA GIT 2.0 (p = 0.05). None Anti-RNA polymerase III patients showed an adequate response in gastrointestinal involvement (0/7) in comparison with other antibodies (0 vs. 25, p = 0,039). Cardiorespiratory involvement remained stable. A total of 12 adverse events were reported with only one withdrawn due to serious adverse effect. CONCLUSIONS: this study suggest that IVIG may improve myositis, gastrointestinal and skin involvement in SSc patients treated in routine care and seems to have a good safety profile.

Mastectomy without radiotherapy: outcome analysis after 10 years of follow-up in a single institution.

The aim of this study was to identify the prognostic factors associated with the risk of loco-regional recurrence (LRR) of women undergoing mastectomy and complete axillary dissection without radiotherapy. We analyzed data from 650 women operated between 1997 and 2001 in a single institution. Median follow-up was 10 years. Overall survival was 89.8 % at 5 years and 76.6 % at 10 years. The 10-year cumulative incidence of LRRs was 10.0 % (5.0, 10.5, 15.8, and 18.5 % in patients with 0, 1-3, 4-9, and ≥10 positive lymph nodes (LNs), respectively). Sixty-two (9.5 %) LRRs were observed, 5 (0.8 %) of which occurred in the axillary LNs. Supraclavicular LNs recurrences (n = 16, 2.5 %) occurred more frequently in patients with four or more positive LNs, Ki-67 ≥ 20 % or extensive peritumoral vascular invasion (PVI). At multivariable analysis, nodal status was the only prognostic factor for local events, while nodal status, Ki-67 and PVI were significant prognostic factors for recurrences in the regional LNs. Moreover, within each category of positive LNs, high values of Ki-67 and extensive PVI were associated with the highest risk of LRR while low values of Ki-67 and absence of extensive PVI were associated with the lowest risk of LRR. Women with node-negative tumors have the lowest risk of LRR and represent the group of patients that might benefit the least from radiotherapy. PVI and Ki-67 might help tailoring PMRT indications among patients with positive LNs. Finally, the very low incidence of recurrences in the axillary LNs raises questions about the inclusion of the axilla in the radiation field.

A comprehensive study of the Gafchromic EBT2 radiochromic film. A comparison with EBT.

PURPOSE: Radiochromic film has become an important tool to assess complex dose distributions. In particular, EBT was accepted by the scientific community as a reference two-dimensional detector. Recently, Gafchromic EBT2 has replaced old film, providing new improvements in both accuracy and handling. METHODS: This work presents a dosimetric study of the new Gafchromic EBT2 using an Epson 10000XL flatbed scanner, also comparing the results with EBT film as reference when necessary. The most important film characteristics have been studied, such as ambient light sensitivity, different possibilities of the three RGB color channels, postirradiation development, high dose behavior, exposition at temperatures similar to the human body, and dependence on orientation during the scanning process. RESULTS: The results obtained confirm a considerably lower sensitivity to ambient light of EBT2, as well as a fast stabilization of the film within 2 h. It has also been found that the green channel has a better behavior at high dose levels up to 35 Gy, in addition to good behavior of the red channel at doses below 10 Gy. Other features, such as temperature independence and scanning orientation dependence, have also been shown. CONCLUSIONS: Gafchromic EBT2 can be used for clinical practice in the same way as the old EBT film. However, a much easier handling as the result of all new enhancements improves film behavior, expanding in this way the potential applications of radiochromic film dosimetry.

Periodontitis and Cardiovascular Diseases. Consensus Report.

Background: In Europe cardiovascular disease (CVD) is responsible for 3.9 million deaths (45% of deaths), being ischaemic heart disease, stroke, hypertension (leading to heart failure) the major cause of these CVD related deaths. Periodontitis is also a chronic non-communicable disease (NCD) with a high prevalence, being severe periodontitis, affecting 11.2% of the world's population, the sixth most common human disease. Material and Methods: There is now a significant body of evidence to support independent associations between severe periodontitis and several NCDs, in particular CVD. In 2012 a joint workshop was held between the European Federation of Periodontology (EFP) and the American Academy of Periodontology to review the literature relating periodontitis and systemic diseases, including CVD. In the last five years important new scientific information has emerged providing important emerging evidence to support these associations. Results and Conclusions: The present review reports the proceedings of the workshop jointly organised by the EFP and the World Heart Federation (WHF), which has updated the existing epidemiological evidence for significant associations between periodontitis and CVD, the mechanistic links and the impact of periodontal therapy on cardiovascular and surrogate outcomes. This review has also focused on the potential risk and complications of periodontal therapy in patients on anti thrombotic therapy and has made recommendations for dentists, physicians and for patients visiting both the dental and medical practices.

Ca2+ and pH determine the interaction of chromaffin cell scinderin with phosphatidylserine and phosphatidylinositol 4,5,-biphosphate and its cellular distribution during nicotinic-receptor stimulation and protein kinase C activation.

Nicotinic stimulation and high K(+)-depolarization of chromaffin cells cause disassembly of cortical filamentous actin networks and redistribution of scinderin, a Ca(2+)-dependent actin filament-severing protein. These events which are Ca(2+)-dependent precede exocytosis. Activation of scinderin by Ca2+ may cause disassembly of actin filaments leaving cortical areas of low cytoplasmic viscosity which are the sites of exocytosis (Vitale, M. L., A. Rodríguez Del Castillo, L. Tchakarov, and J.-M. Trifaró. 1991. J. Cell. Biol. 113:1057-1067). It has been suggested that protein kinase C (PKC) regulates secretion. Therefore, the possibility that PKC activation might modulate scinderin redistribution was investigated. Here we report that PMA, a PKC activator, caused scinderin redistribution, although with a slower onset than that induced by nicotine. PMA effects were independent of either extra or intracellular Ca2+ as indicated by measurements of Ca2+ transients, and they were likely to be mediated through direct activation of PKC because inhibitors of the enzyme completely blocked the response to PMA. Scinderin was not phosphorylated by the kinase and further experiments using the Na+/H+ antiport inhibitors and intracellular pH determinations, demonstrated that PKC-mediated scinderin redistribution was a consequence of an increase in intracellular pH. Moreover, it was shown that scinderin binds to phosphatidylserine and phosphatidylinositol 4,5-biphosphate liposomes in a Ca(2+)-dependent manner, an effect which was modulated by the pH. The results suggest that under resting conditions, cortical scinderin is bound to plasma membrane phospholipids. The results also show that during nicotinic receptor stimulation both a rise in intracellular Ca2+ and pH are observed. The rise in intracellular pH might be the result of the translocation and activation of PKC produced by Ca2+ entry. This also would explain why scinderin redistribution induced by nicotine is partially (26-40%) inhibited by inhibitors of either PKC or the Na+/H+ antiport. In view of these findings, a model which can explain how scinderin redistribution and activity may be regulated by pH and Ca2+ in resting and stimulated conditions is proposed.

Cortical filamentous actin disassembly and scinderin redistribution during chromaffin cell stimulation precede exocytosis, a phenomenon not exhibited by gelsolin.

Immunofluorescence and cytochemical studies have demonstrated that filamentous actin is mainly localized in the cortical surface of the chromaffin cell. It has been suggested that these actin filament networks act as a barrier to the secretory granules, impeding their contact with the plasma membrane. Stimulation of chromaffin cells produces a disassembly of actin filament networks, implying the removal of the barrier. The presence of gelsolin and scinderin, two Ca(2+)-dependent actin filament severing proteins, in the cortical surface of the chromaffin cells, suggests the possibility that cell stimulation brings about activation of one or more actin filament severing proteins with the consequent disruption of actin networks. Therefore, biochemical studies and fluorescence microscopy experiments with scinderin and gelsolin antibodies and rhodamine-phalloidin, a probe for filamentous actin, were performed in cultured chromaffin cells to study the distribution of scinderin, gelsolin, and filamentous actin during cell stimulation and to correlate the possible changes with catecholamine secretion. Here we report that during nicotinic stimulation or K(+)-evoked depolarization, subcortical scinderin but not gelsolin is redistributed and that this redistribution precedes catecholamine secretion. The rearrangement of scinderin in patches is mediated by nicotinic receptors. Cell stimulation produces similar patterns of distribution of scinderin and filamentous actin. However, after the removal of the stimulus, the recovery of scinderin cortical pattern of distribution is faster than F-actin reassembly, suggesting that scinderin is bound in the cortical region of the cell to a component other than F-actin. We also demonstrate that peripheral actin filament disassembly and subplasmalemmal scinderin redistribution are calcium-dependent events. Moreover, experiments with an antibody against dopamine-beta-hydroxylase suggest that exocytosis sites are preferentially localized to areas of F-actin disassembly.

Brain iron accumulation in a blood donor family with restless legs syndrome. / Aumento de los depositos cerebrales de hierro en una familia de donantes de sangre con sindrome de piernas inquietas.

INTRODUCTION: The pathophysiology of restless legs syndrome (RLS) is complex. Secondary RLS with iron deficiency -which suggests disturbed iron homeostasis- remains to be elucidated. CASE REPORTS: We report the findings from a unique blood donor family with RLS. Three blood donors family members were diagnosed with RLS defined by the International RLS Study Group and without history of neurologic diseases and RLS symptoms in the last 3-5 years (range of blood donation: 10-40 years). The neurological examination and electromyographies were normal. A polisomnography showed disturbed nocturnal sleep with a reduction in sleep efficiency and an increased periodic limbs movement index. The cranial MRI showed brain iron deposits in basal ganglia, substantia nigra, red nuclei and dentate nuclei. Phenotypic and genotypic studies rule out genetic haemochromatosis or iron overload. CONCLUSION: The abnormal iron accumulation in the basal ganglia indicated a complex iron metabolism disorder of the central nervous system. Further studies are warranted to confirm our findings and its role in the pathophysiology of RLS.

TITLE: Aumento de los depositos cerebrales de hierro en una familia de donantes de sangre con sindrome de piernas inquietas.Introduccion. La fisiopatologia del sindrome de piernas inquietas (SPI) es compleja. El mecanismo a traves del cual la ferropenia favorece el desarrollo del SPI no esta esclarecido, aunque se sugiere la presencia de una alteracion en la homeostasis cerebral del hierro. Casos clinicos. Se presentan los hallazgos inusuales en una familia de donantes de sangre con SPI. Tres miembros de la misma familia fueron diagnosticados de SPI, cumpliendo los criterios definidos por el grupo internacional para el estudio del SPI (International Restless Legs Syndrome Study Group). Todos eran donantes de sangre habituales (rango de donacion: 10-40 años) y los sintomas de SPI tenian un curso de 3-5 años. La exploracion general y neurologica fue normal en todos los casos, asi como los electromiogramas. El estudio fenotipico y genotipico descarto la presencia de hemocromatosis y otras causas geneticas de sobrecarga cerebral de hierro. Los estudios polisomnograficos mostraron sueño nocturno perturbado, con reduccion de su eficiencia, y un aumento del indice de movimientos periodicos de las piernas. La resonancia magnetica craneal evidencio un aumento de los depositos cerebrales de hierro en los ganglios basales, la sustancia negra, el nucleo rojo y los dentados. Conclusion. Este aumento patologico de los depositos cerebrales de hierro sugiere la presencia de un complejo trastorno del metabolismo cerebral del hierro en nuestros pacientes. Futuros estudios deben confirmar estos hallazgos y profundizar en el estudio de su relacion con la fisiopatologia del SPI.

Factors associated with delirium in critical patients in a health institution in Bucaramanga, Colombia. / Factores asociados con el delírium en pacientes críticos de una institución de salud de Bucaramanga, Colombia.

OBJECTIVE: To determine the incidence and the factors associated with delirium in intensive care unit patients. METHODS: A cohort study conducted on 134 patients in the intensive care unit at a clinic in Bucaramanga, Colombia., who were recruited in the first 24hours following admission and on whom the Richmond Agitation-Sedation Scale (RASS), PRE-DELIRIC version in Spanish, and Confusion Assessment method for Intensive Care Unit (CAM-ICU) were applied; the outcome was evaluated through daily monitoring with CAM-ICU. RESULTS: The incidence of delirium was 20.2%, the predominating type was hypoactive at 66.7%, followed by the hyperactive type at 7.4% and mixed at 25.9%. Fifty-two percent of the patients with delirium died. In the bivariate analysis, the use of sedatives (Relative Risk(RR) 2.4, 95% confidence interval (95% CI) = 1.2-4.5), infection (RR = 2. 8, 95% CI=1.3-5.9), metabolic acidosis (RR = 4 3, 95% CI=2.3-8.0), mechanical ventilation (RR = 4 6, 95% CI=2.0-10.6), aged over 60 years (RR = 2 3, 95% CI=1.09-5.3) and APACHE score greater than 14 (RR = 3. 0) (95% CI=1.1-8.2) were identified as risk factors for delirium. The multivariate analysis only found a relationship with infection (RR = 3 8, 95% CI=1.6-9.1) and being aged over 60 years (RR = 3 2, 95% CI 1.2-8.3). CONCLUSIONS: delirium is frequent in patients in the intensive care unit, especially the hypoactive type. Half of the patients with delirium died. The main risk factors for delirium are infection and being over 60 years age, therefore, delirium prevention activities should focus on these critical patients.

[Study of 30 years on the change in the frequency of esophageal squamous cell carcinoma, esophageal adenocarcinoma and adenocarcinoma of the esophagogastric union]. / Estudio de 30 años sobre el cambio en la frecuencia de carcinoma epidermoide esofágico, adenocarcinoma esofágico y adenocarcinoma de la unión esofagogástrica.

UNLABELLED: Esophageal cancer mortality is high and the incidence of this neoplasm is increasing. OBJECTIVE: Our aim was to compare the frequency of esophageal adenocarcinoma cases (EA) and squamous cell carcinoma (SCC) cases in two study periods (1977-1988 vs. 1989-2006). METHOD: Patients with esophageal cancer or adenocarcinoma of gastroesophageal junction (AGEJ) referred to the Nation al Institute of Medical Sciences and Nutrition "Salvador Zubirán" during 1989-2006 were included. The frequency of EA, SCC was compared with the previously reported series of our institute during 1977-1988. Risk factors for esophageal cancer and AGEJ were investigated. RESULTS: From 1989 to 2006 82 patients were studied, 23 with SCC, 29 with EA and 29 with AGEJ. There was a significant association between gastroesophageal reflux disease (GERD) and EA (OR = 9.5; CI 95% 1.9-48.5, P = 0.0025), and also between GERD and AGEJ (OR 5.6; CI 95% 1.07-28.8, P = 0.03). The association between Barrett's esophagus and EA (OR 14; CI 95% 1.65-119.2, P = 0.0035) and for GEJC (RM 13.6; IC 95% 1.6-116, P = 0.004) was significant. There was an increase in the frequency of AE from 11% (6/57) in the first period to 56% (29/52) in the second period (P < 0.001). The rela tion SCC/EA change from 7:1 in the first period to 0.8:1 in the second. CONCLUSION: There has been an increase in EA, being now the predominant hystologic type of esophageal cancer.

Subclinical cardiovascular disease and Systemic Sclerosis: A comparison between risk charts, quantification of coronary calcium and carotid ultrasonography.

BACKGROUND AND OBJECTIVES: Recently published population-based cohort studies have shown a high prevalence of cardiovascular disease in Systemic Sclerosis (SSc) patients. The aim of this study is to compare three different methods to measure cardiovascular risk in patients with scleroderma. METHODS: Forty-three SSc patients were included. A prospective study was performed for evaluation of cardiovascular risk and subclinical atheromatosis using 3 non-invasive methods: cardiovascular risk tables, carotid Doppler ultrasonography and quantification of coronary calcium by computerized tomography (CT). RESULTS: The cardiovascular risk charts for the Spanish population did not identify patients at high cardiovascular risk. Framingham-REGICOR identified 13 intermediate-risk patients. Twenty-two patients (51.2%) had plaques on carotid ultrasonography. We performed a ROC curve to identify the best cutoff point for the quantification of coronary artery calcium (CACscore), the value of CACscore > 28 AU (Agatston Units) had the highest sensitivity (73%) and specificity (81%) for the diagnosis of subclinical atheromatosis. In the multiple regression study, age and decreased HDL cholesterol levels were identified as independent factors for subclinical atherosclerotic disease. No disease-related factors were associated with increased subclinical arteriosclerosis. CONCLUSION: Carotid ultrasound and CACscore are useful for identifying subclinical atheromatosis in patients with SSc and are superior compared to risk charts used for general population. HDL cholesterol and age were independent factors for the presence of subclinical atherosclerotic disease. A carotid ultrasound or CT should be performed for early detection of subclinical atheromatosis if these factors are present.

First clinical symptom as a prognostic factor in systemic sclerosis: results of a retrospective nationwide cohort study.

The objective of the study is to determine the importance of the mode of onset as prognostic factor in systemic sclerosis (SSc). Data were collected from the Spanish Scleroderma Registry (RESCLE), a nationwide retrospective multicenter database created in 2006. As first symptom, we included Raynaud's phenomenon (RP), cutaneous sclerosis, arthralgia/arthritis, puffy hands, interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), and digestive hypomotility. A total of 1625 patients were recruited. One thousand three hundred forty-two patients (83%) presented with RP as first symptom and 283 patients (17%) did not. Survival from first symptom in those patients with RP mode of onset was higher at any time than those with onset as non-Raynaud's phenomenon: 97 vs. 90% at 5 years, 93 vs. 82% at 10 years, 83 vs. 62% at 20 years, and 71 vs. 50% at 30 years (p < 0.001). In multivariate analysis, factors related to mortality were older age at onset, male gender, dcSSc subset, ILD, PAH, scleroderma renal crisis (SRC), heart involvement, and the mode of onset with non-Raynaud's phenomenon, especially in the form of puffy hands or pulmonary involvement. The mode of onset should be considered an independent prognostic factor in systemic sclerosis and, in particular, patients who initially present with non-Raynaud's phenomenon may be considered of poor prognosis.

Economic evaluation of linezolid versus teicoplanin for the treatment of infections caused by gram-positive microorganisms in Spain.

The aim of this study was to perform a comparative cost-effectiveness analysis of linezolid vs teicoplanin (i.v., switching to oral/i.m. respectively) in Spain. A decision tree model was used with the results of a randomized, comparative, controlled clinical trial with linezolid vs teicoplanin in the treatment of infections caused by Gram-positive microorganisms, with a timeline of 31 days. The efficacy endpoint was the percentage of patients with clinical healing or improvement in their infection. Direct medical costs were included using Spanish 2005 prices. Average cost per patient, average cost-effectiveness ratio and several sensitivity analyses were carried out. In the intent-to-treat (ITT) analysis linezolid obtained a higher percentage of therapeutic success than teicoplanin (95.5% vs 87.6% respectively, p = 0.005), both with similar tolerability. The average cost per treated patient was euro 8,064.76 for linezolid vs euro 8,727.36 for teicoplanin, with an incremental cost of euro 622.59 (-7,6%). Linezolid yielded a lower average cost-effectiveness ratio, euro 8,444.78 (8,195.90 - 8,709.25) than teicoplanin, euro 9,962.74 (9,465.68 - 10,502.23), with a slight reduction in average cost per successfully treated patient of 15.2% ( euro 1,517.96). The results were robust to the sensitivity analysis. In conclusion, linezolid is a more cost-effective option than teicoplanin in the treatment of infections caused by Gram-positive microorganisms, since it offers superior clinical benefits with a lower use of associated resources.

Short-term and long-term effects of diazepam on the memory for discrimination and generalization of scopolamine.

Benzodiazepines are among the most widely prescribed and misused psychopharmaceutical drugs. Although they are well-tolerated, they are also capable of producing amnestic effects similar to those observed after pharmacological or organic cholinergic dysfunction. To date, the effect of benzodiazepine diazepam on the memory for discrimination of anticholinergic drugs has not been reported. The aim of the present study was to analyze the immediate and long-term effects of diazepam on a drug discrimination task with scopolamine. Male Wistar rats were trained to discriminate between scopolamine and saline administration using a two-lever discrimination task. Once discrimination was acquired, the subjects were divided into three independent groups, (1) control, (2) diazepam, and (3) diazepam chronic administration (10 days). Subsequently, generalization curves for scopolamine were obtained. Additionally, the diazepam and control groups were revaluated after 90 days without having been given any other treatment. The results showed that diazepam produced a significant reduction in the generalization gradient for scopolamine, indicating an impairment of discrimination. The negative effect of diazepam persisted even 90 days after drug had been administered. Meanwhile, the previous administration of diazepam for 10 days totally abated the generalization curve and the general performance of the subjects. The results suggest that diazepam affects memory for the stimulus discrimination of anticholinergic drugs and does so persistently, which could be an important consideration during the treatment of amnesic patients with benzodiazepines.