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

Introducción: La trombosis venosa cerebral (TVC) es una causa poco común de ictus que afecta principalmente a adultos jóvenes. Un diagnóstico precoz y preciso puede reducir la tasa y gravedad de las complicaciones. Objetivo: Analizar las características clínicas, manejo y tratamiento de la TVC en diferentes centros de nuestro país. Métodos: Estudio descriptivo retrospectivo multicéntrico de pacientes hospitalizados por TVC entre 2008 y 2017 en 11 centros sanitarios en nuestro país. Resultados: Se incluyeron 256 pacientes, edad media 49,8 ± 18,7 años y el 51% fueron mujeres. Los síntomas más frecuentes fueron: cefalea (73%), déficits focales (50%), crisis epilépticas (33%) y encefalopatía (21%). Las localizaciones más frecuentes fueron: seno longitudinal superior (12,5%), transverso (10,9%) y afectación de dos o más senos o venas (66,4%). La etiología conocida más frecuente fue la trombofilia (24%), siendo la mutación de la protrombina G20210A la más común (19%). El 46% fue tratado con antitrombóticos durante 3-6 meses, el 21% durante un año y un 22,6% de los pacientes requirieron anticoagulación indefinida. En un 5% de los sujetos fue preciso terapia endovascular y un 33% requirió neurocirugía. En relación al pronóstico, el 75% fueron independientes a los 3 meses con una puntuación en la escala de Rankin modificada (mRS) ≤ 2 y la presencia de papiledema (p = 0,03), déficit focal (p = 0,001) y encefalopatía (p < 0,001) se relacionaron significativamente con mal pronóstico (mRS > 3). La tasa de mortalidad intrahospitalaria fue del 4,3% y el 6,3% de los pacientes fallecieron a los 3 meses. Conclusión:La diversidad de factores de riesgo y la presentación variable suponen un desafío en el diagnóstico y tratamiento de la TVC. Para mejorar el pronóstico y reducir la mortalidad es fundamental la instauración de protocolos en el manejo de esta patología.(AU)

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.(AU)

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.

Solvothermal synthesis of soluble, surface modified anatase and transition metal doped anatase hybrid nanocrystals.

Titanium dioxide, or titania, is perhaps the most well-known and widely studied photocatalytic material, with myriad applications, due to a high degree of tunability achievable through the incorporation of dopants and control of phase composition and particle size. Many of the applications of titanium dioxide require particular forms, such as gels, coatings, or thin films, making the development of hybrid solution processable nanoparticles increasingly attractive. Here we report a simple solvothermal route to highly dispersible anatase phase titanium dioxide hybrid nanoparticles from amorphous titania. Solvothermal treatment of the amorphous titania in trifluoroacetic acid leads to the formation of anatase phase nanoparticles with a high degree of size control and near complete surface functionalisation. This renders the particles highly dispersible in simple organic solvents such as acetone. Dopant ions may be readily incorporated into the amorphous precursor by co-precipitation, with no adverse effect on subsequent crystallisation and surface modification.

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.

Survival outcomes in patients aged 75 years and over with peritoneal colorectal carcinomatosis after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC): multicenter study of the Spanish Group of Peritoneal Cancer Surgery (GECOP).

BACKGROUND: The attitude toward cytoreductive surgery with HIPEC in peritoneal carcinomatosis from colorectal cancer is unclear. The aim of this study is to report the perioperative outcomes after cytoreductive surgery with HIPEC in patients ≥ 75 years. METHODS: This retrospective multicenter study collected the data the Spanish Group of Peritoneal Cancer Surgery. Thirty-six patients with peritoneal carcinomatosis from colorectal cancer met the selection criteria for the study. Morbidity, mortality, disease-free and overall survival were analyzed. RESULTS: Morbidity (grade III-IV) was 17% and 2 patients died of complications related to the procedure (5.4%). Median disease-free survival (DFS) was 16 months. DFS at 1 and 3 years was 81% and 42%, respectively. Overall survival at 1 and 3 years was 96% and 75%. In the univariate analysis, preoperative comorbidities (p = 0.01), liver metastases (p = 0.02), blood transfusion (p = 0.001) and postoperative complications (p = 0.001); and in the multivariate analysis, perioperative blood transfusion (OR 2.56, 95% CI 1.95-6.24, p = 0.03) and postoperative complications (OR 3.25, 95% CI 2.35-7.56, p = 0.02) were associated with a lower overall survival. CONCLUSIONS: Age is not an absolute contraindication to perform cytoreduction surgery with HIPEC in highly selected elderly patients with colorectal peritoneal carcinomatosis.

How molecular diagnosis may modify immunotherapy prescription in multi-sensitized pollen-allergic children.

INTRODUCTION: Specific immunotherapy (SIT) is used to treat asthma and allergic rhinitis, and a dose-response relationship has been found for SIT efficacy, creating a need to accurately select the allergen used in therapy. This need is especially pronounced in poly-sensitized children living in areas where different pollen allergen sources coexist in the same season, as this circumstance complicates diagnostic efforts. In such cases, component-resolved diagnosis (CRD) can increase diagnostic accuracy and aid in SIT prescription. MATERIALS AND METHODS: We hypothesized that CRD results would lead to modifications in classical immunotherapy prescription based on sources such as medical history, season of symptom presentation, and skin testing. We studied a sample of children indicated for immunotherapy in whom classical methods had not pointed out the most relevant allergen due to sensitization to more than two pollens. We used a small panel of recombinant allergens, analyzing the percentage of changes to prescription considering the findings of molecular studies. RESULTS: Of the 70 children included, CRD led to modified immunotherapy prescription in 54.3%. Indications of single-allergen therapy increased from 18% to 51% when CRD was included. The decision to prescribe immunotherapy was reversed following CRD in 9.3% of cases. DISCUSSION: CRD use alters the choice of specific immunotherapy in poly-sensitized children. A wide panel of recombinant allergens may not be necessary to improve immunotherapy indication using molecular techniques; rather, a smaller panel adapted to include those allergens prevalent in the geographical area in question appears to be sufficient for more effective immunotherapy, also leading to an improved cost-benefit ratio.

Eventración diafragmática congénita: causa infrecuente de dificultad respiratoria / Congenital diaphragmatic eventration: Rare cause of respiratory distress

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Developments in clinical trials: a Pharma Matters report.

As the pharmaceutical industry strives to meet the ever-increasing complexity of drug development, new technology in clinical trials has become a beacon of hope. With big data comes the promise of accelerated patient recruitment, real-time monitoring of clinical trials, bioinformatics empowerment of quicker phase progression, and the overwhelming benefits of precision medicine for select trials. Risk-based monitoring stands to benefit as well. With a strengthening focus on centralized data by the FDA and industry's transformative initiative, TransCelerate, a new era in trial risk mitigation has begun. The traditional method of intensive on-site monitoring is becoming a thing of the past as statistical, real-time analysis of site and trial-wide data provides the means to monitor with greater efficiency and effectiveness from afar. However, when it comes to big data, there are challenges that lie ahead. Patient privacy, commercial investment protection, technology woes and data variability are all limitations to be met with considerable thought. At the Annual Meeting of the American Academy of Dermatology this year, clinical trials on psoriasis, atopic dermatitis and other skin diseases were discussed in detail. This review of clinical research reports on novel therapies for psoriasis and atopic dermatitis reveals the impact of these diseases and the drug candidates that have been successful in phase II and III studies. Data-focused highlights of novel dermatological trials, as well as real-life big data approaches and an insight on the new methodology of risk-based monitoring, are all discussed in this edition of Developments in Clinical Trials.

Vein thrombosis in a patient with agenesis of inferior vena cava

We report a 29-year-old woman with bilateral deep vein thrombosis. CT-scan was performed and an agenesia of inferior vena cava was found. With regard to the case report, we provide a brief review of the embryogenesis of the inferior vena cava, and of anomalies in the genesis of this vessel. In young patients with idiopathic deep venous thrombosis the existence of an abnormality in the inferior vena cava should be considered

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Comparison of two PCR and one ELISA techniques for the detection of small ruminant lentiviruses (SRLVs) in milk of sheep and goats.

The aim of the present study was to compare the efficiency of two PCR techniques for the diagnosis of small ruminant lentiviruses (SRLVs). Detection of the proviral genome by PCR, though sensitive, is difficult due to the heterogeneity of the SRLV genomes. One of the PCR techniques amplifies a fragment in the pol gene (pol-PCR) and the other PCR targets the LTR region of the proviral genome (LTR-PCR). Milk from 194 sheep and 163 goats from farms in the Central Spain was analyzed by both techniques and compared to results obtained by ELISA. When compared to the serologic assay, the agreement of both PCR techniques was very low (0.024 and 0.020 in sheep, and 0.124 and 0.114 in goats). In view of these results, it may be concluded that the efficacy of PCR for the diagnosis of SRLVs is low and a combination of PCR and ELISA should be used for diagnosis.

Application of fluorescence in situ hybridization as a diagnostic tool in melanocytic lesions, using paraffin wax-embedded tissues and imprint-cytology specimens.

BACKGROUND: Accurate histopathological diagnosis of certain melanocytic skin lesions as benign or malignant can be notoriously difficult. Recently, four-colour fluorescence in situ hybridization (FISH) has emerged as an important tool for classifying these lesions. AIM: To evaluate the sensitivity and specificity of a melanoma FISH probe kit for accurate diagnosis of melanocytic tumours, and to validate its use with imprint-cytology specimens from the cut surface of tumours. METHODS: In total, 50 melanocytic skin lesions (31 malignant melanomas, 10 benign melanocytic naevi, and 9 histologically challenging benign melanocytic skin lesions) were evaluated. The samples comprise 47 tissue specimens embedded in paraffin wax, and three imprint-cytology specimens from the cut surface of melanomas. FISH was performed using four locus-specific identifier probes [Ras responsive element binding protein (RREB)1, myeloblastosis viral oncogene homologue (MYB), cyclin (CCN)D1 and centromere of chromosome (CEP)6], and results were compared with the clinical long-term follow-up and histopathological diagnosis data. RESULTS: The melanoma FISH probe distinguished between naevi and melanomas with a sensitivity of 100% and a specificity of 94.1%. The most sensitive criterion was a gain in 6p25 (RREB1), seen in 100% of cases, followed by CEP6-related MYB loss (48.1%), CCND1 gain (37%) and MYB gain (22.2%). More than three-quarters (77.8%) of melanomas were positive for two or more criteria. Positive FISH results were also obtained for the imprint-cytology specimens. CONCLUSIONS: FISH is a valuable diagnostic tool for differentiating between benign and malignant melanocytic lesions, providing a high degree of sensitivity and specificity. The probes displayed exceptional discriminative capacity in difficult or ambiguous lesions. To our knowledge, his is the first reported use of imprint-cytology specimens for FISH diagnosis.

Long-term survival of simultaneous pancreas-kidney transplantation: influence of early posttransplantation complications.

BACKGROUND: Complications that develop in the early posttransplantation period after simultaneous pancreas-kidney transplantation (SPKT) can contribute to poor long-term survival of grafts and patients. PATIENTS AND METHODS: We studied 86 SPKTs that were performed between 2000 and 2010 in our hospital, analyzing all complications in the early posttransplantation period and their impact on long-term survival in patients and grafts. RESULTS: The mean age of the patients was 38.77 ± 7.13 years (79.1% male). Of the 86 SPKT patients, 22.1% were on peritoneal dialysis (PD) before transplantation, 68.6% were on hemodialysis (HD), and 9.3% had not received any substitutive renal therapy. The immunosuppressive regimens consisted of induction with basiliximab followed by tacrolimus, mycophenolate mofetil, and steroid therapy. More than 75% of patients experienced an infection in the early posttransplantation period: bacteremia (37.2%), central catheter infection (7%), wound infection (4.7%), urinary tract (14%) and positive abdominal drain culture (45.3%). Approximately one third (31.4%) of patients underwent a reoperation, primarily due to bleeding (21.95%) or infection (19.51%). One fifth of patients (19.8%) experienced an acute rejection episode. The 3-year survival of the pancreas was lower among PD patients (82%) compared with patients who did not undergo dialysis before SPKT (100%). The 5-year survival rate of both grafts was lower among patients who underwent a reoperation than those who did not: pancreas survival rates, were 70% versus 93%, respectively (P = .015) and kidney graft survival rates were 75% versus 96%, respectively (P = .0017). Five-year patient survival rates were also lower among reoperated patients than those who were not (85% vs 97%, respectively), although the difference was not significant (P = .27). CONCLUSIONS: Complications in the early posttransplantation period after SPKT were frequent, increasing morbidity and inpatient stay. One third of our patients underwent a reoperation, which had a negative impact on graft survival.

Diagnostic performance of PCR and ELISA on blood and milk samples and serological survey for small ruminant lentiviruses in central Spain.

The diagnostic performance of an ELISA for the detection of antibodies to the small ruminant lentiviruses (SRLVs) maedi-visna virus and caprine arthritis-encephalitis virus in milk and corresponding blood samples was evaluated in 50 sheep. The agreement between ELISA results in blood and milk was 90 per cent, and the κ value was 0.79. In addition, a serological survey in the central zone of Spain was performed using milk samples from 413 animals (250 sheep and 163 goats) from 12 flocks/herds. All flocks/herds had some animals that were positive for SRLV. Among the animals, 60.0 per cent of the sheep and 8.0 per cent of the goats tested were seropositive. Each sample was also tested using a PCR technique, which increased the percentage of positive animals detected. Using a combination of ELISA and PCR gave a total of 72.2 per cent of sheep and 28.8 per cent of goats positive for SRLV.

Characterization of a mouse model overexpressing beta-site APP-cleaving enzyme 2 reveals a new role for BACE2.

BACE2 is homologous to BACE1, a beta-secretase that is involved in the amyloidogenic pathway of amyloid precursor protein (APP), and maps to the Down syndrome critical region of chromosome 21. Alzheimer disease neuropathology is common in Down syndrome patients at relatively early ages, and it has thus been speculated that BACE2 co-overexpression with APP would promote the early neurodegenerative phenotype. However, the in vivo function of BACE2 has not yet been elucidated. The aim of the present work has been to analyse the impact of in vivo BACE2 overexpression using a transgenic mouse model. Our results suggest that BACE2 is not involved in the amyloidogenic pathway, cognitive dysfunction or cholinergic degeneration. However, TgBACE2 animals showed increased anxiety-like behaviour along with increased numbers of noradrenergic neurones in locus coeruleus, thus suggesting an unexpected role of BACE2 overexpression.

Utilidad de la ecografía de la sustancia negra en el diagnóstico diferencial de la enfermedad de Parkinson / The value of ultrasound imaging of the substantia nigra in the differential diagnosis of Parkinson's disease

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The role of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinomatosis in recurrent ovarian cancer

BACKGROUND AND OBJECTIVES: Peritoneal carcinomatosis in women frequently has an ovarian origin. Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) along with radical surgery/peritonectomy could present a new therapeutic approach with curative intention. The purpose of this research is to evaluate the role of the administration of HIPEC. METHODS: A series of patients (N=26) diagnosed with peritoneal carcinomatosis for recurrent epithelial ovarian cancer (stage III) from January 1997 to December 2004 submitted to radical surgery/peritonectomy with optimal cytoreduction (R0-R1) were included in this study, 14 treated with HIPEC and 12 without HIPEC. RESULTS: The variables age, histologic type, peritonectomy procedures, peritoneal cancer index (PCI) and lymph node affectation were similar in both groups. The 5-year global survival was 58% and 17% (p=0.046), and 67% and 29% in patients with maximal cytoreduction (R0) (p=0.264), in the HIPEC- and non-HIPEC-treated patients, respectively. In patients with optimal cytoreduction and partial peritonectomy, 5-year global survival was also superior in the HIPEC group (75% vs. 11%, p=0.011). Average time free of disease was superior in the HIPEC group (48+/-42 vs. 24+/-21 months), with less reinterventions due to a new reappearance during the first three evolutionary years (2/14 vs. 4/12). Postoperative morbidity did not show substantial differences in both groups and there was no surgical mortality. CONCLUSIONS: HIPEC is a complement to radical surgery/ peritonectomy, which has been shown to be a surgical procedure with high tolerability, low morbimortality, enhanced survival and prolonged disease-free interval in patients with peritoneal carcinomatosis for recurrent ovarian cancer (AU)

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One hundred one simultaneous pancreas-kidney transplantations: long-term outcomes at a single center.

INTRODUCTION: Among patients with type 1 diabetes mellitus and end-stage renal disease, simultaneous pancreas-kidney (SPK) transplantation is associated with increased survival compared with solitary kidney transplants or dialysis. METHODS: A retrospective, descriptive study was performed on 101 consecutive SPK transplantation performed in our center over the last 20 years. We excluded six pancreas alone, eight pancreas after kidney, and four retransplantations. We analyzed demographic characteristics and patient and graft survivals. We also compared patient and pancreatic graft survivals between three periods: 1989 to 1999, 2000 to 2003, and 2004 to 2007. In the first period, bladder drainage was performed in all patients. In the second and third periods, it was replaced by enteric drainage. RESULTS: Overall patient survival was 83.2%. Kidney graft loss occurred in 12 (11.8%) patients and pancreas graft loss in 21 (20.7%) patients. Overall pancreatic graft survival was 79.2% with a 1-year value of 87.1%. By periods, pancreatic graft survival was 75% during the bladder drainage era; 76.9% in the second period; and 85.7% in the third period (P = .88). CONCLUSION: SPK transplantations in diabetic patients with end-stage renal disease were associated with improving pancreas graft survival throughout the study period.