Performance of Saliva Specimens for the Molecular Detection of SARS-CoV-2 in the Community Setting: Does Sample Collection Method Matter?

Data on the performance of saliva specimens for diagnosing coronavirus disease 2019 (COVID-19) in ambulatory patients are scarce and inconsistent. We assessed saliva-based specimens for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse transcriptase PCR (RT-PCR) in the community setting and compared three different collection methods. This prospective study was conducted in three primary care centers. RT-PCR was performed on paired nasopharyngeal swabs (NPS) and saliva samples collected from outpatients with a broad clinical spectrum of illness. To assess differences in collection methods, saliva specimens were obtained in a different way in each of the participating centers: supervised collection (SVC), oropharyngeal washing (OPW), and self-collection (SC). Pairs of NPS and saliva samples from 577 patients (median age, 39 years; 44% men; 42% asymptomatic) were collected and tested, and 120 (20.8%) gave positive results. The overall agreement with NPS results and kappa coefficients (κ) for saliva samples obtained by SVC, OPW, and SC were 95% (κ = 0.85), 93.4% (κ = 0.76), and 93.3% (κ = 0.76), respectively. The sensitivities (95% confidence intervals [95% CI]) of the saliva specimens ranged from 86% (72.6% to 93.7%) for SVC to 66.7% (50.4% to 80%) for SC samples. Sensitivity was higher for samples with lower cycle threshold (CT ) values. The best RT-PCR performance was observed for SVC, with sensitivities (95% CI) of 100% (85.9% to 100%) in symptomatic individuals and 88.9% (50.7% to 99.4%) in asymptomatic individuals at CT values of ≤30. We conclude that saliva is an acceptable specimen for the detection of SARS-CoV-2 in the community setting. Specimens collected under supervision perform comparably to NPS and can effectively identify individuals at higher risk of transmission under real-life conditions.

Purkinje cell-specific Grip1/2 knockout mice show increased repetitive self-grooming and enhanced mGluR5 signaling in cerebellum.

Cerebellar Purkinje cell (PC) loss is a consistent pathological finding in autism. However, neural mechanisms of PC-dysfunction in autism remain poorly characterized. Glutamate receptor interacting proteins 1/2 (Grip1/2) regulate AMPA receptor (AMPAR) trafficking and synaptic strength. To evaluate role of PC-AMPAR signaling in autism, we produced PC-specific Grip1/2 knockout mice by crossing Grip2 conventional and Grip1 conditional KO with L7-Cre driver mice. PCs in the mutant mice showed normal morphology and number, and a lack of Grip1/2 expression. Rodent behavioral testing identified normal ambulation, anxiety, social interaction, and an increase in repetitive self-grooming. Electrophysiology studies revealed normal mEPSCs but an impaired mGluR-LTD at the Parallel Fiber-PC synapses. Immunoblots showed increased expression of mGluR5 and Arc, and enhanced phosphorylation of P38 and AKT in cerebellum of PC-specific Grip1/2 knockout mice. Results indicate that loss of Grip1/2 in PCs contributes to increased repetitive self-grooming, a core autism behavior in mice. Results support a role of AMPAR trafficking defects in PCs and disturbances of mGluR5 signaling in cerebellum in the pathogenesis of repetitive behaviors.

Periodontal disease in adults with diabetes, prevalence and risk factors. Results of an observational study.

AIM: We sought (a) to assess the association between periodontal disease and diabetes, controlling for socio-demographic characteristics, comorbidities, oral health status and lifestyle variables; (b) to identify which of these variables are independently associated with periodontal disease among diabetes sufferers. METHODS: We conducted a case-control study using data from the National/European Health Interview Surveys, conducted from 2003 to 2014 in Spain. We included 65 295 subjects ≥40 years. Diabetes status was self-reported. One non-diabetic control was matched by the year-of-survey, age and sex for each diabetic patient. The presence of periodontal disease was defined using the answer "my teeth bleed spontaneously or while brushing" or/and "my teeth move" to the following question: "Do you suffer of any of these dental and oral disorders or disease?". Independent variables included demographic, socio-economic and healthcare related variables, oral health status and comorbidities. RESULTS: The prevalence of periodontal disease was higher among those suffering from diabetes than their non-diabetes controls (23.8% vs 19.5%; P < 0.001). Adjusted OR of periodontal disease for subjects with diabetes was 1.22 (95% CI; 1.03-1.45). Among diabetes sufferers, missing teeth status (OR 2.08, 95% CI; 1.70-2.53), suffering osteoporosis (OR 1.41, 95% CI; 1.07-1.63) and suffering depression (OR 1.39, 95% CI; 1.12-1.71) were positively associated with higher risk of periodontal disease. Older ages, using private insurance and university education level were associated with lower rates of periodontitis. CONCLUSIONS: Diabetes subjects have an increased likelihood of periodontal disease. Dentists and physicians should increase their awareness with their diabetic patients, especially those with lower educational level, with missing teeth, osteoporosis and depression.

[Idiopathic intracranial hypertension and spontaneous cerebrospinal fluid fistula. Usefulness of intracranial pressure monitoring]. / Hipertensión intracraneal idiopática y fístula espontánea de líquido cefalorraquídeo. Utilidad de la monitorización de la presión intracraneal.

Spontaneous cerebrospinal fluid (CSF) fistulas are rather common in daily practice. The aim of the surgical treatment is closure of the leak, but recurrences are quite frequent. The association between spontaneous CSF fistulas and idiopathic intracranial hypertension (IIH) is not uncommon, and this is probably the cause of the low rate of success of the surgical treatment. Symptoms of IIH associated with spontaneous CSF fistula are atypical, and diagnosis is often missed. Continuous intracranial pressure monitoring is very useful in the diagnosis of chronic IIH and in patients with spontaneous CSF fistula, as it helps in making decisions on the treatment of these patients.

[Endovascular versus surgical treatment in subarachnoid haemorrhage: Cost analysis]. / Costes del tratamiento endovascular frente al quirúrgico en hemorragia subaracnoidea aneurismática.

OBJECTIVES: To analyse costs of endovascular versus surgical treatment in 80 patients with aneurysmal subarachnoid haemorrhage (aSAH). MATERIAL AND METHODS: We analysed data on 80 consecutive patients with aSAH between January 2010 and June 2011. Endovascular treatment was used in 57 patients and surgical in 23 patients. Demographic (gender and age) and clinical data (Hunt-Hess and Fisher scales), length of stay (ICU and ward) and results at 6 months (Glasgow outcome scale,[GOS]) were collected. Costs including stay, follow-up, complications and retreatments were calculated. RESULTS: Age was higher in the endovascular group (statistically significant). There were no differences between the 2 groups in Hunt-Hess and Fisher scales. Results at 6 months were also similar, although slightly better in the surgical group. Length of stay was longer in surgical patients, both in ICU (mean 1.4 days) and ward (1.7 days). Hospitalisation length was also related to age and Hunt-Hess and Fisher scales. Costs from embolisation devices, follow-up and retreatment (12% in this series) made final endovascular treatment 4.1% more expensive than surgical treatment (€35,835 versus €34,404). Endovascular procedure (including retreatments) was 110% more expensive than surgical treatment (€8,015 versus €3,817). CONCLUSIONS: There are no differences between the 2 treatments in terms of morbidity and mortality. Stability of surgical treatment was higher than that of endovascular, with better occlusion and lower retreatment rates. Endovascular treatment is more expensive in ruptured aneurysms, principally due to embolisation device costs, long-term follow-up and retreatments, in retreatments, in spite of shorter hospital stay. In incidental aneurysms, which usually need shorter hospitalisation, differences between the 2 treatments could be even larger.

[Usefulness of intracranial pressure continuous monitoring in pseudotumor cerebri]. / Utilidad de la monitorización de la presión intracraneal en pacientes con sospecha de hipertensión intracraneal benigna.

OBJECTIVES: To analyse the usefulness of intracranial pressure (ICP) monitoring in pseudotumor cerebri (PTC). MATERIAL AND METHODS: Ten patients with suspected PTC, but having incomplete criteria for the syndrome, on whom ICP monitoring was performed. Demographic, clinical and radiological data were collected, as well as ICP monitoring data and related complications. Results were evaluated 6 months after surgery. RESULTS: In relation to demographics, all patients were young females. Mean ICP was less than 250 mmH2O in 5 of 8 patients with pathological monitoring. Most patients (62.5%) showed A waves; these were related with higher mean ICP, but not always with papilloedema. All recordings showed high amplitude B waves. Most pathological recordings showed wave amplitudes superior to 5 mmHg. There were no complications related to the monitoring technique. CONCLUSIONS: Clinical and lumbar opening pressure data are not enough to establish PTC diagnosis correctly, especially if patient has been treated previously. Monitoring using ICP is a valuable, safe tool, and very useful in this syndrome. Mean ICP could be normal even with pathological recordings. Morphological analysis is necessary to establish diagnosis. A and B waves are highly related to shunt response. Wave amplitude is related to brain compliance and to shunt response as well.

[Usefulness of continuous intracranial pressure monitoring in long-standing overt ventriculomegaly in adults]. / Utilidad de la monitorización de la presión intracraneal en pacientes con ventriculomegalia marcada de larga evolución.

OBJECTIVES: To analyze the usefulness of intracranial pressure (ICP) monitoring in overt long-standing ventriculomegaly patients. MATERIAL AND METHODS: There were 22 patients with ventriculomegaly and neurological symptoms. Demographic, clinical and radiological data were collected, as well as ICP monitoring data and complications related to the procedure. Results were evaluated 6 months after surgery. RESULTS: Mean age was 44 years (22-70). Mean Evans index was 0.47 (0.35-0.66). Aqueductal stenosis was present in more than half of the patients (55%). Mean ICP was higher than 12 mmHg in only 9% of patients. Morphological analysis of ICP recordings was abnormal in 64% of patients. "Pre-plateau" A waves were seen in 7 patients, with B waves seen in 20 patients (high amplitude B waves in 14). Twelve patients were operated on the basis of ICP recordings (CSF shunt or ventriculostomy). Seventy per cent of treated patients had improved at 6 months. There were no complications related to the monitoring technique. CONCLUSIONS: ICP monitoring is a valuable, safe tool, very useful in these cases. Selection of surgical candidates on the basis of ICP monitoring seems to be advisable. Mean ICP may be normal even with pathological recordings. Morphological analysis is essential to establish a correct diagnosis. The presence of A and B waves in the recording is highly related to good shunt response.

Terson's syndrome after endoscopic removal of a colloid cyst.

An extremely rare complication of endoscopic colloid cyst removal is presented. Terson's syndrome related to endoscopic resection of a colloid cyst has been reported only twice before in the literature and it could be explained by intracranial hypertension related to rinsing during the procedure. The case is described and the complications in the neuroendoscopic removal of colloid cyst are reviewed from the literature.

MIR4435-2HG as a possible novel predictive biomarker of chemotherapy response and death in pediatric B-cell ALL.

Introduction: Although B-cell acute lymphoblastic leukemia (B-cell ALL) survival rates have improved in recent years, Hispanic children continue to have poorer survival rates. There are few tools available to identify at the time of diagnosis whether the patient will respond to induction therapy. Our goal was to identify predictive biomarkers of treatment response, which could also serve as prognostic biomarkers of death, by identifying methylated and differentially expressed genes between patients with positive minimal residual disease (MRD+) and negative minimal residual disease (MRD-). Methods: DNA and RNA were extracted from tumor blasts separated by immunomagnetic columns. Illumina MethlationEPIC and mRNA sequencing assays were performed on 13 bone marrows from Hispanic children with B-cell ALL. Partek Flow was used for transcript mapping and quantification, followed by differential expression analysis using DEseq2. DNA methylation analyses were performed with Partek Genomic Suite and Genome Studio. Gene expression and differential methylation were compared between patients with MRD-/- and MRD+/+ at the end of induction chemotherapy. Overexpressed and hypomethylated genes were selected and validated by RT-qPCR in samples of an independent validation cohort. The predictive ability of the genes was assessed by logistic regression. Survival and Cox regression analyses were performed to determine the association of genes with death. Results: DAPK1, BOC, CNKSR3, MIR4435-2HG, CTHRC1, NPDC1, SLC45A3, ITGA6, and ASCL2 were overexpressed and hypomethylated in MRD+/+ patients. Overexpression was also validated by RT-qPCR. DAPK1, BOC, ASCL2, and CNKSR3 can predict refractoriness, but MIR4435-2HG is the best predictor. Additionally, higher expression of MIR4435-2HG increases the probability of non-response, death, and the risk of death. Finally, MIR4435-2HG overexpression, together with MRD+, are associated with poorer survival, and together with overexpression of DAPK1 and ASCL2, it could improve the risk classification of patients with normal karyotype. Conclusion: MIR4435-2HG is a potential predictive biomarker of treatment response and death in children with B-cell ALL.

[Adult chronic idiopathic hydrocephalus-diagnosis, treatment and evolution. Prospective study]. / Hidrocefalia crónica del adulto: diagnóstico, tratamiento y evolución. Estudio prospectivo.

INTRODUCTION: At present, chronic hydrocephalus or normal pressure hydrocephalus (NPH) has a controversial diagnosis in which multiple diagnostic and therapeutic techniques have been used with variable degrees of postoperative success. The aim of our study is to evaluate a number of patients diagnosed with adult chronic idiopathic hydrocephalus who were treated with a CSF shunt at our centre between 2006 and 2009 through clinical scales and radiological controls pre- and postoperatively. MATERIAL AND METHODS: We prospectively analysed 40 patients. The diagnosis of idiopathic NPH was established when patients met 3 criteria: (i)clinical; (ii)radiological (Evans >0.3), and (iii)hydrodynamic (Katzman infusion test with Rout >12) or pathological ICP monitoring (B waves in over 20% of a nocturnal registration). We used a low-pressure DVP 5/35 GAV in all cases. Clinical assessments were conducted at 3, 6 and 12 months and radiological assessments at 6 months postoperatively. The clinical improvement of patients was assessed with the NPH, modified RANKIN and modified PFEIFFER rating scales. RESULTS: The study of risk factors (age, gender, smoking, drinking, arterial hypertension, diabetes mellitus, dyslipidemia) did not establish statistically significant relationships. A statistically significant improvement was observed (P<.01) in the NPH and RANKIN tests at 3, 6 and 12 months. Clinical improvement values obtained were: NPH 73%, 74% and 64%, and RANKIN 54%, 72% and 56%, respectively. The PFEIFFER scale only showed a significant improvement at 12 months. These improvements were classified into various levels (high, moderate, mild and no improvement). The initial mean Evans index was 0.385, and 0.3675 postoperatively. There was only one infection of the valvular system (2%) without further complications. Morbidity and mortality related to the procedure were 0%. CONCLUSION: An appropriate selection of patients through clinical, radiological, hydrodynamic and ICP monitoring criteria enables us to obtain good results and a low complication rate.

Symptomatic sacral Tarlov cyst: Case report and review of literature.

Tarlov cysts are a common finding in MRI. Most of them are asymptomatic but in some cases can cause pain in urogenital region. Diagnosis and treatment are controversial and most of the symptomatic cases are not well diagnosed and treated because of unawareness of neurosurgeons about them. Treatment of symptomatic TC is effective and good results have been published with percutaneous and surgical techniques. A case of a young woman with a symptomatic sacral cyst treated surgically successfully is presented and literature about it is reviewed.

Inflammatory Cytokines Associated with Multiple Sclerosis Directly Induce Alterations of Neuronal Cytoarchitecture in Human Neurons.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) coined by inflammation and neurodegeneration. The actual cause of the neurodegenerative component of the disease is however unclear. We investigated here the direct and differential effects of inflammatory mediators on human neurons. We used embryonic stem cell-derived (H9) human neuronal stem cells (hNSC) to generate neuronal cultures. Neurons were subsequently treated with tumour necrosis factor alpha (TNFα), interferon gamma (IFNγ), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 17A (IL-17A) and interleukin 10 (IL-10) separately or in combination. Immunofluorescence staining and quantitative polymerase chain reaction (qPCR) were used to assess cytokine receptor expression, cell integrity and transcriptomic changes upon treatment. H9-hNSC-derived neurons expressed cytokine receptors for IFNγ, TNFα, IL-10 and IL-17A. Neuronal exposure to these cytokines resulted in differential effects on neurite integrity parameters with a clear decrease for TNFα- and GM-CSF-treated neurons. The combinatorial treatment with IL-17A/IFNγ or IL-17A/TNFα induced a more pronounced effect on neurite integrity. Furthermore, combinatorial treatments with two cytokines induced several key signalling pathways, i.e. NFκB-, hedgehog and oxidative stress signalling, stronger than any of the cytokines alone. This work supports the idea of immune-neuronal crosstalk and the need to focus on the potential role of inflammatory cytokines on neuronal cytoarchitecture and function.

Cerebellopontine angle meningiomas: LINAC stereotactic radiosurgery treatment.

OBJECTIVES: To evaluate the efficacy of treatment with linear accelerator-based stereotactic radiosurgery (LINAC) in cerebellopontine angle meningiomas. METHODS: We analyzed 80 patients diagnosed with cerebellopontine angle meningiomas between 2001 and 2014, treated with stereotactic radiosurgery (SRS), of whom 81.9% (n=68) were women, with an average age of 59.1 years (32-79). SRS was applied as primary treatment in 83.7% (n=67) and in 16.3% (n=13) as an adjuvant treatment to surgery. SRS treatment was provided using LINAC (Varian 600, 6MeV) with M3 micromultilamines (brainLab) and stereotactic frame. The average tumor volume was 3.12cm3 (0.34-10.36cm3) and the coverage dose was 14Gy (12-16Gy). We performed a retrospective descriptive analysis and survival analysis was performed with the Kaplan-Meier method and multivariate analysis to determine those factors predictive of tumor progression or clinical improvement. RESULTS: After an average follow-up period of 86.9 months (12-184), the tumor control rate was 92.8% (n=77). At the end of the study, there was an overall reduction in tumor volume of 32.8%, with an average final volume of 2.11cm3 (0-10.35cm3). The progression-free survival rate at 5, 10 and 12 years was 98%, 95% and 83.3% respectively. The higher tumor volume (p=0.047) was associated with progression. There was clinical improvement in 26.5% (n=21) of cases and clinical worsening in 16.2% (n=13). Worsening is related to the radiation dose received by the brainstem (p=0.02). Complications were 8.7% (7 cases) of hearing loss, 5% (4 cases) of brain radionecrosis, and 3.7% (3 cases) of cranial nerve V neuropathy. Hearing loss was related to initial tumor size (p=0.033) and maximum dose (p=0.037). The occurrence of radionecrosis with the maximum dose (p=0.037). CONCLUSIONS: Treatment of cerebellopontine angle meningiomas with single-dose SRS using LINAC is effective in the long term. Better tumor control rates were obtained in patients with small lesions.

Long-term Experience of LINAC Single-Dose Radiosurgery for Skull Base Meningiomas: A Retrospective Single-Center Study of 241 Cases.

BACKGROUND AND OBJECTIVES: Stereotactic radiosurgery (SRS) is increasingly applied to treat meningiomas, attributable to their increased incidence in older individuals at greater surgical risk. To evaluate the effectiveness of treatment with linear accelerator (LINAC)-based stereotactic radiosurgery in skull base meningiomas as either primary treatment or postresection adjuvant therapy. METHODS: This study included 241 patients diagnosed with skull base meningiomas treated by single-dose SRS, with a median age of 59 years. SRS was primary treatment in 68.1% (n = 164) and adjuvant treatment in 31.9% (n = 77), using LINAC (Varian 600, 6 MeV). The median tumor volume was 3.2 cm 3 , and the median coverage dose was 14 Gy. Bivariate and multivariate analyses were performed to determine predictive factors for tumor progression, clinical deterioration, and complications. Kaplan-Meier analysis was used for survival analysis. RESULTS: After the median follow-up of 102 months, the tumor control rate was 91.2% (n = 220). Progression-free survival rates were 97.07%, 90.1%, and 85.7% at 5, 10, and 14 years, respectively. Clinical improvement was observed in 56 patients (23.2%). In multivariate analysis, previous surgery (hazard ratio 3.8 [95%CI 1.136-12.71], P = .030) and selectivity (hazard ratio .21 [95%CI 0.066-0.677], P = .009) were associated with tumor progression and increased maximum dose (odds ratio [OR] 4.19 [95% CI 1.287-13.653], P = .017) with clinical deterioration. The permanent adverse radiation effect rate was 6.2% (n = 15) and associated with maximum brainstem dose >12.5 Gy (OR 3.36 [95% CI .866-13.03], P = .08) and cerebellopontine angle localization (OR 3.93 [95% CI 1.29-11.98], P = .016). CONCLUSION: Treatment of skull base meningiomas with single-dose SRS using LINAC is effective over the long term. Superior tumor control is obtained in patients without previous surgery. Adverse effects are related to localization in the cerebellopontine angle, and maximum brainstem radiation dose was >12.5 Gy.

Brain lymphoma development related to a long lasting epidermoid cyst.

INTRODUCTION: Epidermoid cysts (EC) are benign and slow growing lesions. A primary brain lymphoma development related to a EC is presented, second case described in literature. CASE PRESENTATION: A woman 40 years old, harbouring a EC for more than 20 years, develops a fast growing brain lesion next to the EC. Surgery was performed and diagnosis was primary diffuse B cells lymphoma. DISCUSSION: Malignant transformation of EC has been described, usually to squamous cells carcinoma, and much less frequently, to another tumours. Inflammatory mechanisms have been advocated to explain this evolution. Chronic inflammation and lymphoma genesis are related, and this could be the mechanism behind this rare evolution of an EC. CONCLUSIONS: Even being benign lesions, EC can develop malignant tumours due to the chronic inflammation secondary to them.

Response to neoadjuvant chemotherapy and survival of children and adolescents with high-grade osteosarcoma treated based on the EURAMOS-1 protocol.

BACKGROUND: High-grade osteosarcoma is the most common malignant bone tumor in children and adolescents. This study aimed to evaluate the histologic response to neoadjuvant chemotherapy and overall and event-free survival rates in patients < 21 years of age with a diagnosis of conventional osteosarcoma. METHODS: We conducted an analytical and observational study of a cohort of patients < 21 years old with a diagnosis of conventional osteosarcoma treated with the OS INC-2009 protocol (based on EURAMOS-1). Descriptive analysis was performed, and overall and event-free survival rates were calculated by the Kaplan-Meier method. RESULTS: Between April 2009 and October 2016, 84 patients with conventional osteosarcoma (mean age 13.5 ± 3.2 years) were admitted. Metastatic disease at diagnosis was observed in 36 patients (42.8%). Of the 41 patients who received neoadjuvant chemotherapy (50.6%), 15 (36.6%; confidence interval [95% CI]: 49.9-75.6) were classified as good responders and 26 (63%; 95% CI: 22.5-58.0) as poor responders. The 5-year overall and event-free survival rates in good responders were 88.8% (95% CI: 43.3-98.3) and 81.4% (95% CI: 43.5-95.0); in poor responders it was 66.5% (95% CI: 40.7-83.1) and 31.4% (95% CI: 13.8-50.7), respectively. CONCLUSIONS: Good responders' evaluation of histologic response to neoadjuvant chemotherapy showed improved overall and event-free survival rates. Specialized centers with multidisciplinary and comprehensive management are required to make the application of high-toxicity protocols feasible.

INTRODUCCIÓN: El osteosarcoma de alto grado es el tumor óseo maligno más común en niños y adolescentes. El objetivo de este trabajo fue evaluar la respuesta histológica a la quimioterapia neoadyuvante y la supervivencia global y libre de eventos en pacientes menores de 21 años con diagnóstico de osteosarcoma convencional. MÉTODOS: Se llevó a cabo un estudio observacional analítico de una cohorte de pacientes menores de 21 años con diagnóstico de osteosarcoma convencional tratados con el protocolo OS INC-2009 (basado en EURAMOS-1). Se realizó el análisis descriptivo y se calcularon la supervivencia global y la supervivencia libre de eventos por el método de Kaplan-Meier. RESULTADOS: Entre abril de 2009 y octubre de 2016 se analizaron 84 pacientes con osteosarcoma convencional, cuya edad promedio fue de 13.5 años (desviación estándar: ± 3.2). La enfermedad metastásica al diagnóstico se observó en 36 pacientes (42.8%). De los 41 (50.6%) pacientes que recibieron terapia neoadyuvante, 15 (36.6%; intervalo de confianza del 95% [IC95%]: 49.9-75.6) se clasificaron como buenos respondedores y 26 (63%; IC95%: 22.5-58.0) como malos respondedores. Las supervivencias global y libre de eventos a 5 años en los buenos respondedores fueron del 88.8% (IC95%: 43.3-98.3) y el 81.4% (IC95% 43.5-95.0), y en los malos respondedores fueron del 66.5% (IC95%: 40.7-83.1) y el 31.4% (IC95%: 13.8-50.7), respectivamente. CONCLUSIONES: La evaluación de la respuesta histológica a la quimioterapia neoadyuvante de los pacientes buenos respondedores muestra unas mejores supervivencias global y libre de eventos. Se requieren centros especializados con manejos multidisciplinarios e integrales para hacer factible la aplicación de protocolos con alta toxicidad.

Brain lymphoma development related to a long lasting epidermoid cyst. / Desarrollo de un linfoma cerebral con relación a un quiste epidermoide de larga evolución.

INTRODUCTION: Epidermoid cysts (EC) are benign and slow growing lesions. A primary brain lymphoma development related to a EC is presented, second case described in literature. CASE PRESENTATION: A woman 40 years old, harbouring a EC for more than 20 years, develops a fast growing brain lesion next to the EC. Surgery was performed and diagnosis was primary diffuse B cells lymphoma. DISCUSSION: Malignant transformation of EC has been described, usually to squamous cells carcinoma, and much less frequently, to another tumours. Inflammatory mechanisms have been advocated to explain this evolution. Chronic inflammation and lymphoma genesis are related, and this could be the mechanism behind this rare evolution of an EC. CONCLUSIONS: Even being benign lesions, EC can develop malignant tumours due to the chronic inflammation secondary to them.

Performance of the cobas u 701 Analyzer in Urinary Tract Infection Screening.

BACKGROUND: Negative urine cultures to rule out urinary tract infections (UTI) generate a considerable laboratory workload; thus, a rapid screening test is desirable. We evaluated the performance of a new automated microscopy analyzer, cobas u 701 (Roche Diagnostics International, Rotkreuz, Switzerland) for the screening of UTI, and developed a rule-out strategy to reduce the number of samples requiring culture. We also assessed squamous epithelial cell (SEC) count as a predictor of culture contamination. METHODS: In total, 1,604 urine samples from outpatients were analyzed with cobas u 701 and culture. Bacterial (BAC) and white blood cell (WBC) counts were used for sample interpretation. To determine a useful cut-off point to predict negative cultures, we selected the highest sensitivity and specificity values obtained from ROC curves. Diagnostic accuracy by age and gender was evaluated. RESULTS: Urine culture showed growth of ≥104 colony forming units (CFU)/mL in 256 samples (16.0%). The highest sensitivity (91.8%) and specificity (68.4%) were obtained for cut-off points of 119 BAC/µL and 22 WBC/µL. The combination of BAC and WBC improved the performance of the rule-out strategy with a low rate of false-negative results (1.5%) and a high negative predictive value (NPV, 97.3%). Fifty-seven percent of the samples would not have required culture. SEC count was a poor predictor of culture contamination. CONCLUSIONS: cobas u 701 can substantially reduce the number of urine samples requiring culture, with a low false-negative rate and a high NPV.

MR Elastography-Based Assessment of Matrix Remodeling at Lesion Sites Associated With Clinical Severity in a Model of Multiple Sclerosis.

Magnetic resonance imaging (MRI) with gadolinium based contrast agents (GBCA) is routinely used in the clinic to visualize lesions in multiple sclerosis (MS). Although GBCA reveal endothelial permeability, they fail to expose other aspects of lesion formation such as the magnitude of inflammation or tissue changes occurring at sites of blood-brain barrier (BBB) disruption. Moreover, evidence pointing to potential side effects of GBCA has been increasing. Thus, there is an urgent need to develop GBCA-independent imaging tools to monitor pathology in MS. Using MR-elastography (MRE), we previously demonstrated in both MS and the animal model experimental autoimmune encephalomyelitis (EAE) that inflammation was associated with a reduction of brain stiffness. Now, using the relapsing-remitting EAE model, we show that the cerebellum-a region with predominant inflammation in this model-is especially prone to loss of stiffness. We also demonstrate that, contrary to GBCA-MRI, reduction of brain stiffness correlates with clinical disability and is associated with enhanced expression of the extracellular matrix protein fibronectin (FN). Further, we show that FN is largely expressed by activated astrocytes at acute lesions, and reflects the magnitude of tissue remodeling at sites of BBB breakdown. Therefore, MRE could emerge as a safe tool suitable to monitor disease activity in MS.

Longitudinal study on mitochondrial effects of didanosine-tenofovir combination.

Tenofovir disoproxil fumarate (TDF) has been reported to be free of adverse effects on mitochondria. We evaluate the effects of the introduction of TDF in a didanosine (ddI)-based highly active antiretroviral therapy (HAART) on mitochondrial DNA (mtDNA) content, mitochondrial mass (MM), and cytochrome c oxidase (COX) activity of the oxidative phosphorylation (OXPHOS) system over a 12-month period. Forty-four asymptomatic HIV patients with undetectable viral load receiving a ddI-based HAART were recruited and switched to ddI plus TDF (ddI + TDF) and nevirapine (n = 22) or maintained with the same baseline ddIbased HAART scheme (n = 22). Peripheral blood mononuclear cells were obtained at 0, 6, and 12 months. COX activity and MM were determined by spectrophotometry and the mtDNA content by quantitative realtime PCR. The mtDNA content showed a progressive decrease over the 12-month period of the study for the two groups with respect to baseline, with such a decrease statistically significant only in the ddI + TDF group (55% decrease, p < 0.001). In addition, the decrease of mtDNA content over time was statistically different between both groups (p < 0.001). Consistently, MM and COX activity decreased significantly at 12 months with respect to baseline only in the ddI < TDF group (28% decrease for MM, p < 0.05; 47% decrease for COX activity, p < 0.001). We conclude that switching to a HAART regimen containing ddI + TDF is associated with evolutive mitochondrial damage expressed as mtDNA depletion, loss of MM, and decrease in COX efficiency. The particular relevance of either ddI, TDF, or any interaction between them in such a mitochondrial dysfunction remains to be established.