Management of cerebral venous thrombosis in Spain: MOTIVATE descriptive study.

INTRODUCTION: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults. Early, accurate diagnosis can reduce the rate and severity of complications. OBJECTIVE: The aim of this study was to analyse the clinical characteristics, management, and treatment of CVT in different centres in Spain. METHODS: We conducted a multicentre, retrospective, descriptive study of patients hospitalised due to CVT between 2008 and 2017 at 10 Spanish centres. RESULTS: We included 256 patients, with a mean age (SD) of 49.8 (18.7) years; 51% of patients were women. The most frequent symptoms were headache (73%), focal deficits (50%), epileptic seizures (33%), and encephalopathy (21%). The most frequent localisations were the superior sagittal sinus (12.5%), the transverse sinus (10.9%), and 2 or more sinuses or veins (66.4%). Thrombophilia was the most frequent known aetiology (24%), and was most commonly associated with the prothrombin G20210A mutation (19%). Forty-six percent of patients were treated with antithrombotics for 3 to 6 months, 21% for one year, and 22.6% required indefinite anticoagulation. Endovascular therapy was performed in 5% of cases, and 33% required neurosurgery. Regarding outcomes, 75% of patients were independent at 3 months (modified Rankin Scale [mRS] score ≤ 2), with papilloedema (P =  .03), focal deficits (P = .001), and encephalopathy (P < .001) showing a statistically significant association with poor prognosis (mRS > 3). The in-hospital mortality rate was 4.3%, with a 3-month mortality rate of 6.3%. CONCLUSION: The diverse risk factors and variable presentation of CVT represent a challenge in the diagnosis and treatment of this condition. To improve prognosis and reduce mortality, it is essential to establish management protocols for this entity.

Management of cerebral venous thrombosis in Spain: MOTIVATE descriptive study. / Manejo de la trombosis venosa cerebral en España: estudio descriptivo MOTIVATE.

INTRODUCTION: Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults. Early, accurate diagnosis can reduce the rate and severity of complications. OBJECTIVE: The aim of this study was to analyse the clinical characteristics, management, and treatment of CVT in different centres in Spain. METHODS: We conducted a multicentre, retrospective, descriptive study of patients hospitalised due to CVT between 2008 and 2017 at 11 Spanish centres. RESULTS: We included 256 patients, with a mean age (SD) of 49.8 (18.7) years; 51% of patients were women. The most frequent symptoms were headache (73%), focal deficits (50%), epileptic seizures (33%), and encephalopathy (21%). The most frequent localisations were the superior sagittal sinus (12.5%), the transverse sinus (10.9%), and 2 or more sinuses or veins (66.4%). Thrombophilia was the most frequent known aetiology (24%), and was most commonly associated with the prothrombin G20210A mutation (19%). Forty-six percent of patients were treated with antithrombotics for 3-6 months, 21% for one year, and 22.6% required indefinite anticoagulation. Endovascular therapy was performed in 5% of cases, and 33% required neurosurgery. Regarding outcomes, 75% of patients were independent at 3 months (modified Rankin Scale [mRS] score ≤ 2), with papilloedema (P=.03), focal deficits (P=.001), and encephalopathy (P <.001) showing a statistically significant association with poor prognosis (mRS> 3). The in-hospital mortality rate was 4.3%, with a 3-month mortality rate of 6.3%. CONCLUSION: The diverse risk factors and variable presentation of CVT represent a challenge in the diagnosis and treatment of this condition. To improve prognosis and reduce mortality, it is essential to establish management protocols for this entity.

Rose Bengal test: diagnostic yield and use for the rapid diagnosis of human brucellosis in emergency departments in endemic areas.

The aim of the present study was to analyse the diagnostic yield of the rose Bengal test for the rapid diagnosis of human brucellosis in an emergency department in an area where the disease is endemic. The study included 711 patients diagnosed initially with brucellosis and 270 controls. Brucellosis patients were divided into three groups: group I, individuals with no regular exposure to or history of brucellosis; group II, individuals exposed repeatedly to Brucella infection; and group III, individuals infected with Brucella who had received appropriate treatment during the previous 12 months. Blood cultures were positive for 445 (62.6%) brucellosis patients, while the remaining 266 (37.4%) patients were diagnosed according to clinical and serological criteria. The overall sensitivity of the rose Bengal test was 92.9%. The specificities for groups I, II and III were 94.3%, 91.7% and 76.9%, respectively, with positive likelihood ratios of 16.5, 10.4 and 4.2, respectively. The diagnostic gain after the performance of the rose Bengal test was good or very good in patients with no previous exposure to Brucella or history of brucellosis, but poor in patients who were exposed repeatedly to Brucella or had a history of brucellosis and a low pre-test probability. Use of the rose Bengal test as the sole technique for the diagnosis of brucellosis in endemic areas should be considered very carefully in the context of patients who are exposed repeatedly to Brucella or have a history of brucellosis.

Rapid diagnosis of human brucellosis by SYBR Green I-based real-time PCR assay and melting curve analysis in serum samples.

The aim of this study was to develop a LightCycler-based real-time PCR (LC-PCR) assay and to evaluate its diagnostic use for the detection of Brucella DNA in serum samples. Following amplification of a 223-bp gene sequence encoding an immunogenetic membrane protein (BCSP31) specific for the Brucella genus, melting curve and DNA sequencing analysis was performed to verify the specificity of the PCR products. The intra- and inter-assay variation coefficients were 1.3% and 6.4%, respectively, and the detection limit was 5 fg of Brucella DNA (one genome equivalent). After optimisation of the PCR assay conditions, a standard curve was obtained with a linear range (correlation coefficient=0.99) over seven orders of magnitude from 10(7) to 10 fg of Brucella DNA. The LC-PCR assay was found to be 91.9% sensitive and 95.4% specific when tested with 65 negative control samples and 62 serum samples from 60 consecutive patients with active brucellosis. The assay is reproducible, easily standardised, minimises the risk of infection in laboratory workers, and has a total processing time of <2 h. It could therefore form a promising and practical approach for the rapid diagnosis of human brucellosis.

Complications associated with Brucella melitensis infection: a study of 530 cases.

We carried out a prospective study of 530 patients older than 14 years of age with brucellosis. We describe the incidence and clinical features of the focal forms of the disease, analyzing some of the possible factors associated with their appearance. One hundred sixty-nine patients (31.9%) had a focal form or complication. Osteoarticular complications were the most frequent, totaling 113 cases (66%), followed by genitourinary with 18 cases (5.1% of males), hepatic (2.5%), neurologic (1.7%), and heart (1.5%). Nine patients (1.7%) had more than 1 complication. In a multivariate analysis, diagnostic delay greater than 30 days (OR 2.0), ESR > 40 mm/hr (OR 1.9), and levels of alpha-2 globulin > 7.5 g/L (OR 6.8) were statistically significant independent variables associated with the presence of focal forms. Twenty-five patients with complications (14.8%) required surgical treatment. The relapse rate was 3.6% for those patients without complications and 4.1% for patients with focal forms (p > 0.05). However, when therapeutic failure, relapses, and mortality were considered together, the risk of an unfavorable evolution was significantly greater in patients with focal forms (10.6% versus 3.6% in patients without complications; OR 1.9, 95% CI 1.4-7.1, p < 0.005). Given the worse prognosis, knowledge and early diagnosis of the focal forms of B. melitensis infection is especially important.

Diagnostic usefulness of percutaneous liver biopsy in HIV-infected patients with fever of unknown origin.

OBJECTIVES: to determine the value of percutaneous liver biopsy (PLB) in the diagnosis of fever of unknown origin (FUO) in HIV-infected patients and establish a prediction model for its usefulness to enable diagnosis of FUO in these patients to be standardized. METHODS: a total of 58 HIV-infected patients who underwent PLB for the evaluation of FUO were studied at 'Carlos Haya' Hospital in Malaga, Spain. The patients were classified into three groups, according to the results of the PLB: (a) diagnostic PLB (when a definitive diagnosis was obtained); (b) helpful PLB (the tissue sample showed suggestive, but not definitive, findings); and (c) normal or non-specific PLB (no contribution to diagnosis, the findings being normal or irrelevant). Multivariate analysis was made to establish a prediction model for the diagnostic usefulness of PLB, calculating the positive (PPV) and negative (NPV) predictive values. RESULTS: PLB was carried out in 58 HIV-infected patients during diagnosis of FUO. Risk factors for HIV infection included intravenous drug use (72.4%), homosexual or bisexual activities (12.1%), and heterosexual transmission (15.5%). Fifty-two out of 58 patients (89.6%) had previous AIDS-defining illnesses. The mean CD4 lymphocyte count +/-SD was 56.4+/-80.9/mm3. The mean duration of fever was 43 days. Diagnosis could be established in 51 (87.9%) patients, with tuberculosis (50%) and leishmaniasis (20.7%) being the most common. The PLB was diagnostic in 25 cases (43.1%), helpful in 13 (22.4%), and normal or non-specific in the remaining 20 (34.5%). Biopsy-associated complications occurred in two cases. The presence of hepatomegaly or splenomegaly were the most useful factors in predicting the usefulness of the PLB, with a PPV of 86.1% and NPV of 68.2%. In patients with tuberculosis, an increased alkaline phosphatase and hepatomegaly had a PPV of 86.4% and a NPV of 71.4%. CONCLUSIONS: PLB is a useful technique for the diagnosis of FUO in HIV-infected persons. Early PLB should be considered in those patients with hepatosplenomegaly and increased alkaline phosphatase levels.

[Incidence and current clinical spectrum of tuberculosis in a metropolitan area in the south of Spain]. / Incidencia y espectro clínico actual de la tuberculosis en un área sanitaria metropolitana del sur de España.

BACKGROUND: To study the incidence and clinical spectrum of tuberculosis in the metropolitan area of Málaga (Spain). METHODS: Prospective study which includes all patients who had a diagnosis of tuberculosis within the referral area of "Carlos Haya" Málaga Regional Hospital from March 1, 1993 to February 28, 1994. RESULTS: During the study period, there were 138 cases of tuberculosis, with an incidence of 43.7 cases/10(5) inhabitants. Ninety one cases (66%) were male, and the mean age (SD) was 33.2 (18.3), with 88% being less than 55 years old. Thirty six patients (26.1%) were HIV-infected. Extrapulmonary tuberculosis made up 27.5% of the cases, and was more frequent in HIV-infected patients (p < 0.01; odds ratio: 2.9; 95% CI: 1.2-7.1). The mean (SD) time to diagnosis was 54.3 (76) days. The diagnosis was microbiologically confirmed in 106 cases (76.8%), histologically in 14 cases (10.1%), and the remaining 18 cases (13.1%) were clinically diagnosed. The global rate of resistance was 10.8%. The rate of primary resistance was 4.6%, and the rate of multidrug-resistant tuberculosis was 3.1%. Eighty nine patients (77.4%) were cured, six patients (5.2%) stopped the treatment, 3 (2.6%) had relapses and 1 (0.9%) was considered a therapeutic failure; 16.7% of patients were lost for follow-up. Sixteen patients died and in nine of them (6.5%) the death was attributed to tuberculosis. CONCLUSIONS: The incidence of tuberculosis in Málaga urban area is high. It mainly affects young males of unfavored socio-economic classes. HIV-infected patients account for a high percentage of the cases. The high number of productive cases and the long time to diagnosis evidence the shortcomings of our sanitary system. These facts, together with the high rate of non-compliance, of treatment may explain the seriousness of the current situation in our country.

[Reversible cerebral vasoconstriction syndrome following smoking cessation and treatment with bupropion]. / Sindrome de vasoconstriccion cerebral reversible tras abandono de habito tabaquico y tratamiento con bupropion.

TITLE: Sindrome de vasoconstriccion cerebral reversible tras abandono de habito tabaquico y tratamiento con bupropion.

No association of TAP and LMP genetic polymorphism in human brucellosis and its complications.

Molecules involved in antigen processing (LMP) and peptide transport (TAP) are coded by polymorphic genes. This polymorphism may influence the peptide antigen selection process and play a role in the pathogenesis of human brucellosis. We studied the polymorphism of the antigen processing and transport genes (LMP and TAP) in 61 patients with human brucellosis and 102 controls from southern Spain. We found no differences in the frequencies of the LMP and TAP genotypes between the patients and the controls. Study of the patients with and without focal or complicated forms showed a significant increase in the TAP2A/TAP2F genotype in those with focal forms compared with those without focal forms (16% vs 0%, p = 0.02), though this difference lost its significance after correction for the number of comparisons. This study suggests that larger studies will be needed to confirm or rule out the possible association of the TAP2A/TAP2F genotype or other possible associations with focal forms of brucellosis.

Short communication: contribution of the immunovirological state and traditional cardiovascular risk factors to low HDL-cholesterol in HIV patients.

The prevalence of low HDL-C levels in an HIV population and its related factors was investigated. We undertook a multicenter, cross-sectional study of all HIV patients on regular follow-up in five hospitals (Southern Spain). A physical examination and fasting laboratory analysis were performed and a questionnaire about cardiovascular risk factors was provided. One thousand and seventy-two patients were included, 43.8% of whom had low HDL-C levels. The prevalence of low HDL-C was higher among patients diagnosed with AIDS, those not on antiretroviral therapy, those with a detectable HIV viral load, those with CD4 cell counts ≤350 cells/µl, smokers, and those with hypertriglyceridemia. For patients on antiretroviral therapy, the prevalence of low HDL-C was higher for those on protease inhibitors than those taking nonnucleoside reverse transcriptase inhibitors. In the multivariate analysis, low HDL-C levels were associated with tobacco use (OR 1.37, 95% CI 1.04-1.8; p = 0.04), hypertriglyceridemia (OR 2.94, 95% CI 2.2-3.8; p < 0.00001), CD4 cells count ≤350 cells/µl (OR 1.74, 95% CI 1.2-2.3; p < 0.0001), and a detectable HIV viral load (OR 1.85, 95% CI 1.3-2.5; p < 0.0001). The immunological and virological conditions, in addition to traditional cardiovascular risk factors such as tobacco use and hypertriglyceridemia, affect HDL-C levels in HIV-infected patients. For patients on antiretroviral therapy, the use of protease inhibitors is associated with a higher probability of low levels of HDL-C. Although it is not clear if the higher HDL-C levels associated with antiretroviral use are surrogates for decreased cardiovascular disease risk, this may be another reason to start antiretroviral therapy earlier.

Comparison of seven commercial DNA extraction kits for the recovery of Brucella DNA from spiked human serum samples using real-time PCR.

We compared the relative recovery of extraction of bacterial DNA from serum using seven commercial kits (UltraClean DNA BloodSpin Kit, Puregene DNA Purification System, Wizard Genomic DNA Purification Kit, High Pure PCR Template Preparation Kit, GFX Genomic Blood DNA Purification Kit, NucleoSpin Tissue Kit, and QIAamp DNA Blood Mini Kit). Human serum samples were spiked with known concentrations of Brucella melitensis Rev 1; the DNA was extracted and tested in genus-specific LightCycler polymerase chain reaction (PCR). The UltraClean DNA BloodSpin Kit proved to be as sensitive as the QIAamp DNA Blood Mini Kit isolation method and could detect down to 100 fg of DNA, though only the former had no contamination. All the other procedures yielded DNA isolation results that were less sensitive and were always contaminated. Our results show that the UltraClean DNA Blood Spin Kit was the commercially available assay tested that yielded the best sensitivity, purity, and lack of contamination for Brucella DNA isolation from serum.

Usefulness of a quantitative real-time PCR assay using serum samples to discriminate between inactive, serologically positive and active human brucellosis.

Diagnosis of brucellosis can be difficult in certain scenarios where conventional microbiological techniques have important limitations. The aim of this study was to develop a LightCycler Quantitative PCR assay in serum samples to discriminate between active and past brucellosis. In total, 110 serum samples from 46 brucellosis patients and 64 controls, including persons who had recently been treated for brucellosis, asymptomatic persons exposed to brucellosis, and patients with febrile syndromes involving a differential diagnosis with brucellosis, were studied. Brucella spp.-specific sequences of the PCR primers and probe were selected from the gene encoding an immunogenic membrane protein of 31 kDa (BCSP31). The analytical sensitivity was 1 x 10(1) fg of Brucella DNA. The mean threshold cycles for brucellosis patients and controls were 31.8 +/- 1.7 and 35.4 +/- 1.1, respectively (p <0.001). The best cut-off for bacterial DNA load was 5 x 10(3) copies/mL. At this cut-off, the area under the receiver operating characteristic curves was 0.963 (95% CI 0.920-1.005), with a sensitivity of 93.5% and a specificity of 98.4%. Under the assay conditions, the LightCycler Quantitative PCR in serum samples seems to be highly reproducible, rapid, sensitive and specific. It is therefore a useful method for both the initial diagnosis and the differentiation between past and active brucellosis.

Polymorphism of the transmembrane region of the MICA gene and human brucellosis.

We investigated the polymorphism of the transmembrane region of the MICA gene (major histocompatibility complex class I chain-related gene A) in relation to susceptibility to human brucellosis. We typed 114 patients with brucellosis and 121 healthy controls for MICA transmembrane polymorphism with polymerase chain reaction methods combined with fluorescent technology. We found a significant decrease in the frequency of the MICA-A4 allele in the patients with brucellosis compared with the controls (4.4% vs 10.3%, Pc = 0.03). The frequency of the MICA-A5 allele was increased in the group of patients with focal complications (15% vs 38%, Pc = 0.004). Our data suggest the MICA-A4 allele shows a tendency to be protective against infection by Brucella melitensis. Furthermore, the MICA-A5 allele appears to confer susceptibility to focal forms in patients with brucellosis.

Real time polymerase chain reaction: a new powerful tool for the diagnosis of neurobrucellosis.

BACKGROUND/METHODS: We compared the diagnostic yield of a real time polymerase chain reaction (PCR) assay in cerebrospinal fluid (CSF) samples with conventional microbiological techniques for the diagnosis of neurobrucellosis. Following amplification of a 223 bp sequence specific for Brucella genus, melting curve analysis was performed to verify the specificity of the PCR products. RESULTS: All six patients with neurobrucellosis (three meningitis and three meningoencephalitis) had a positive real time PCR assay, whereas CSF cultures and Wright seroagglutination tests were positive in only two and four cases, respectively. Brucella specific amplicons were easily demonstrated by their characteristic melting temperature in all the real time PCR assays. CONCLUSION: LightCycler based real time PCR assay in CSF samples is more rapid and sensitive than conventional microbiological tests. This technique could be useful for the rapid diagnosis of neurobrucellosis.