Prognosis of glioblastoma patients improves significantly over time interrogating historical controls.

BACKGROUND: Glioblastoma (GBM) is the most common devastating primary brain cancer in adults. In our clinical practice, median overall survival (mOS) of GBM patients seems increasing over time. METHODS: To address this observation, we have retrospectively analyzed the prognosis of 722 newly diagnosed GBM patients, aged below 70, in good clinical conditions (i.e. Karnofsky Performance Status -KPS- above 70%) and treated in our department according to the standard of care (SOC) between 2005 and 2018. Patients were divided into two groups according to the year of diagnosis (group 1: from 2005 to 2012; group 2: from 2013 to 2018). RESULTS: Characteristics of patients and tumors of both groups were very similar regarding confounding factors (age, KPS, MGMT promoter methylation status and treatments). Follow-up time was fixed at 24 months to ensure comparable survival times between both groups. Group 1 patients had a mOS of 19 months ([17.3-21.3]) while mOS of group 2 patients was not reached. The recent period of diagnosis was significantly associated with a longer mOS in univariate analysis (HR=0.64, 95% CI [0.51 - 0.81]), p < 0.001). Multivariate Cox analysis showed that the period of diagnosis remained significantly prognostic after adjustment on confounding factors (adjusted Hazard Ratio (aHR) 0.49, 95% CI [0.36-0.67], p < 0.001). CONCLUSION: This increase of mOS over time in newly diagnosed GBM patients could be explained by better management of potentially associated non-neurological diseases, optimization of validated SOC, better management of treatments side effects, supportive care and participation in clinical trials.

Molecular and clinical diversity in primary central nervous system lymphoma.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity. PATIENTS AND METHODS: To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data. RESULTS: Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue. CONCLUSIONS: The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions.

Venous leg ulcer in the context of chronic venous disease.

OBJECTIVES: Chronic venous disease (CVD) is a frequent disorder with a high socioeconomic impact. Little is known about the possible differences between healed ulcer (C5 group) and active ulcer (C6 group) in terms of disease severity and quality of life (QoL). Our aim was to determine the possible differences in severity disease and QoL between the C5-C6 and C1 (control) group. METHODS: Data from a national, multicentre, observational and cross-sectional study (n = 1598) were used to compare three groups of CVD: C1 (n = 243), C5 (n = 136) and C6 (n = 70). CVD severity was assessed with the Venous Clinical Severity Score (VCSS) and QoL with the Short Form 12 Health Survey (SF-12) and Chronic Lower Limb Venous Insufficiency Questionnaire (CIVIQ-20). RESULTS: Patients with active ulcers had a higher mean total VCSS than patients with healed ulcers (P < 0.05). Both SF-12 and CIVIQ-20 QoL questionnaires indicated a poorer QoL in patients with ulcers than in those with C1 (P < 0.05). Compared with the C5 group, patients with active ulcers (C6) had lower QoL scores, but the differences were not statistically significant. CONCLUSIONS: Patients with venous leg ulcers (C5-C6) are associated with high severity and poor QoL. However, the healing of a leg ulcer did not contribute to improvement of QoL.

Quality of life in patients with chronic venous disease: influence of the socio-demographical and clinical factors.

AIM: Chronic venous disease (CVD) is a well-defined and known disorder which impact on related-health quality of life (QoL). However, individuals factors which determinate quality of life on CVD are not well defined. The purposes of this study were to describe the QoL in patients with CVD and examine socio-demographical and clinical factors which influence QoL METHODS: One thousand five hundred sixty patients with CVD were evaluated. We calculated for each patient two disease-specific severity scores: The "C" grade (clinical) of the CEAP classification and the Venous Clinical Severity Score (VCSS). Additionally, two QoL questionnaires were recorded: Short-Form Health Survey (SF-12) and Chronic Lower Limb Venous Insufficiency Questionnaire (CIVIQ-20). Two multivariate logistic regression analyses (SF-12 and CIVIQ-20 model) were conducted to determine whether demographic and clinical variables were independently associated with QoL. RESULTS: Both QoL questionnaires indicated that the QoL decreased significantly (P<0.05) as the C grade of CEAP increased. Each increase of 0.10 in VCSS score represented 2% worsening in QoL as measured by CIVIQ-20. Three factors were strongly associated with poor QoL on SF-12: increasing age, prior superficial venous thrombosis (SVT) or prior deep venous thrombosis. In the specific disease CIVIQ-20 questionnaire three factors (higher age, prior SVT and higher weight) were strongly associated with decrease QoL. CONCLUSION: Increasing disease severity by VCSS is associated with reductions in QoL. Subgroup analysis indicates that there are several significant individual determinants of worsening QoL.

Chronic venous disease in Spain: doctor-patient correlation.

AIM: The present study aimed to demonstrate how the quality of life (QoL) perceived by patients with chronic venous disease (CVD) is correlated with the severity of their disease objectively assessed by primary care physician. MATERIAL AND METHODS: A total of 1560 patients with CVD were evaluated using four measurement instruments: CEAP clinical classification, Venous Clinical Severity Score (VCSS), SF-12 Health Survey and Chronic Lower Limb Venous Insufficiency Questionnaire (CIVIQ-20). Statistical correlations between these tools were analysed using Spearman's coefficient. RESULTS: Patients were distributed in C0, 58 (3.7%); C1, 243 (15.6%); C2, 328 (21.0%); C3, 357 (22.9%); C4, 368 (23.6%); C5, 136 (8.7%); and C6, 70 (4.5%). The VCSS score for the whole cohort was 0.89 ± 0.53. The correlation between CEAP and VCSS was moderately strong (r = 0.69). The overall QoL scores measured by SF and CIVIQ were 56.84 ± 19.63 and 65.11 ± 14.35, respectively. The correlation between the two QoL questionnaires was very strong (r = 0.81). The correlations of the SF and CIVIQ with the VCSS were moderately strong (r = -0.47 and -0.48). The correlations between QoL questionnaires and CEAP were moderate and lower than those with VSCC. CONCLUSIONS: While there is correlation between VCSS, CEAP, modified CIVIQ and venous ultrasound findings, subgroup analysis indicates that this correlation is driven by different components of VCSS compared with the other venous assessment tools. Patients' opinions about their disease are correlated with those assessed by primary care physicians.

[News on venous thromboembolic disease]. / Novedades en la enfermedad tromboembólica venosa.

This paper brings together the latest developments that have occurred in different aspects of venous thromboembolism (VTE): VTE prophylaxis in high-risk orthopedic surgery and acutely ill hospitalized medical patients; therapeutic advances in pulmonary embolism and superficial vein thrombosis and VTE future prospects. It summarizes the reviews that five speakers made in-depth for the Second Day in New Anticoagulant Treatment, held in Madrid on November 18, 2011, organized by the Foundation for the Study of Thromboembolic Disease in Spain and endorsed by the Spanish Society of Internal Medicine, Spanish Society of Pneumology and Thoracic Surgery, Spanish Society of Cardiology, Spanish Society of Thrombosis and Haemostasis and the Spanish Society of Angiology and Vascular Surgery.

The sialyl Lewis X analogue, CY-1503, down-regulates leucocyte-endothelium interactions and the inflammatory response.

OBJECTIVE: To elucidate mechanisms of protection of ischaemic liver with the sialyl Lewis X analogue CY-1503 by regulation of inflammatory mediators such as oxygen free radicals and cytokines as well as blocking the migration of leucocytes. DESIGN: Laboratory study. SETTING: Teaching hospital, Spain. ANIMALS: 122 male Sprague-Dawley rats divided into four groups: normal (n = 18), sham-operated (n = 28), ischaemic controls (n = 38), and CY-1503 (n = 38). INTERVENTIONS: Warm total hepatic ischaemia for 90 minutes followed by various periods of reperfusion. MAIN OUTCOME MEASURES: Survival, liver histology, liver function, neutrophil infiltration, and free radical and cytokine concentrations. RESULTS: 2/20 ischaemic controls survived, compared with 14/20 given CY-1503. Liver function was better, as was histological appearance judged by the Suzuki score); myeloperoxidase activity was significantly decreased (n = 6 in each group, p<0.01) as were concentrations of free radicals (n = 12 in each group, p<0.05) in the group given CY-1503. CY-1503 had no effect on concentrations of the cytokines tumour necrosis factor-alpha or interleukin 1-alpha. CONCLUSIONS: CY-1503 exerts a protective effect in that it able to down-regulate concentrations of free radicals in our rat model. It is a potent inhibitor of neutrophil migration, but has no effect on cytokine concentrations.

Protective effect of exogenous nitric oxide on the renal function and inflammatory response in a model of ischemia-reperfusion.

BACKGROUND: Tissue subjected to a period of ischemia undergoes morphological and functional damage that increases during the reperfusion phase. The aim of the present work was to assess the possible improvement induced by exogenous administration of nitric oxide (NO) on renal injury and inflammatory reaction in an experimental animal model of renal ischemia-reperfusion (I-R). METHODS: Ischemia was achieved by ligation of the left arteria and vein for 60 min, followed first by contralateral nephrectomy and then reestablishment of blood flow. Molsidomine, used as an NO donor, was administered by systemic injection 30 min before reperfusion. The effect of molsidomine was compared with the effect of hydralazine, a non-NO donor hypotensive agent. RESULTS: Treatment with molsidomine improved the renal dysfunction (increase in plasma creatinine and urea levels) caused by I-R. Moreover, molsidomine blunted the enhanced production of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL] 1alpha), the increase in tissular levels of superoxide anions and oxygen free radical scavengers, and the neutrophilic infiltration observed in the ischemic kidney. One hundred percent survival was achieved in the group of animals treated with the NO donor, whereas the groups of animals undergoing I-R that did not receive molsidomine showed a 40% mortality from the second day after reperfusion. CONCLUSIONS: The present work demonstrated that systemic treatment with an NO donor before reperfusion improved renal function and diminished inflammatory responses in a kidney subjected to an I-R process.

[Nutrition and bacterial translocation]. / Nutrición y translocación bacteriana.

The present work is part of a presentation given at the Scientific Meeting of the Association for Surgical Nutrition and Metabolism, during the XX National Congress for Surgery (Madrid, November 1994). The authors, prior to presenting their experiences, define and high light the importance of the phenomenon of "Bacterial Translocation" (BT). Afterwards, and based on several experimental studies performed by them, they attempt to answer two questions: 1) Is the term BT correct? 2) Is BT a physiological or a pathological state? Finally they review the relationship which exists between bacterial translocation and nutrition, both from a causative point of view as from the prevention and therapy of the same.

[An experimental model of bacterial translocation]. / Modelo experimental sobre translocación bacteriana.

The authors submit an experimental model for bacterial translocation (administering OF-1 mice Zymosan intra-peritoneally at a dose of 1 mg/kg weight). The existence is confirmed of this new mechanism of infection (0% of translocation in control groups, as against 80% in the trial group -p < 0.001). The bacteria in the translocated organs coincide with those present in the fecal flora of the experimental animal. This study is the point of departure for subsequent research to study the physiopathological mechanisms of the phenomenon, which will enable us subsequently to reach better preventive and/or therapeutic decisions.

[Pseudomembranous colitis after surgery for a ruptured abdominal aortic aneurysm]. / Colitis pseudomembranosa después de cirugía por aneurisma aórtico abdominal roto.

We present a rare postoperative complication after surgical procedures for rupture of abdominal aortic aneurysms. The disease, a pseudomembranous colitis, was early recognized (by evidence of clostridium difficile after a coprocultive) and satisfactorily treated with vancomycin. From the literature review we found only a similar case but results were absolutely different from our case.

Peri-incisional and preoperative administration of cefmetazole for the prophylaxis of wound infection after appendicectomy.

The tissue and blood levels of Cefmetazole are compared after preoperative administration of a single dose of 30 mg/K body weight of the antibiotic administered intravenously (15 patients) and peri-incisionally (30 patients) to patients scheduled for emergency appendicectomy. Local and general tolerance to the antibiotic was good by both routes. No local or general complications arose in any of the patients. As expected, the tissue concentrations achieved with peri-incisional infiltration were significantly higher than those obtained by the intravenous route. With the blood levels, exactly the opposite happens at the start of the operation whereas at the end, there were no significant differences between the two routes employed. The prophylactic administration by peri-incisional infiltration is an easy and safe method which provides high tissue concentrations simultaneously with adequate blood levels and should be considered as useful in the preoperative administration of antibiotics for prophylaxis.

Multiseptate gallbladder.

Nine cases of multiseptate gallbladder have been reported in the English literature. Another case is presented. We consider cholecystectomy the treatment of choice because it relieves the symptoms and avoids chronic infection and stone formation.

[Logical use of prophylactic antibacterial agents in infectious post-appendectomy complications. A controlled clinical trial]. / Uso lógico de antimicrobianos profilácticos en las complicaciones infecciosas post-apendicectomía. Estudio clínico controlado.

A prospective clinical trial is carried out in 88 patients undergoing surgery for removal of the appendix. Authors show the efficacy of the association of pre and postoperative gentamycin plus clindamycin or lincomycin in prevention of postoperative infections, which, in the cases with non-ruptured appendix was 0%, and in gangrenous or perforated cases was 8.6%, with a global infection rate of 6% in this prophylactic subgroup I. However, when the same antibiotics are administered only postoperatively (subgroup II), global infection rate is of 34.2% similar to data in the literature in which no antibiotics were given. There have been no complications derived from this antibiotic prophylaxis.