Comparative effectiveness and cost-effectiveness of natalizumab and fingolimod in rapidly evolving severe relapsing-remitting multiple sclerosis in the United Kingdom.

AIM: To evaluate the real-world comparative effectiveness and the cost-effectiveness, from a UK National Health Service perspective, of natalizumab versus fingolimod in patients with rapidly evolving severe relapsing-remitting multiple sclerosis (RES-RRMS). METHODS: Real-world data from the MSBase Registry were obtained for patients with RES-RRMS who were previously either naive to disease-modifying therapies or had been treated with interferon-based therapies, glatiramer acetate, dimethyl fumarate, or teriflunomide (collectively known as BRACETD). Matched cohorts were selected by 3-way multinomial propensity score matching, and the annualized relapse rate (ARR) and 6-month-confirmed disability worsening (CDW6M) and improvement (CDI6M) were compared between treatment groups. Comparative effectiveness results were used in a cost-effectiveness model comparing natalizumab and fingolimod, using an established Markov structure over a lifetime horizon with health states based on the Expanded Disability Status Scale. Additional model data sources included the UK MS Survey 2015, published literature, and publicly available sources. RESULTS: In the comparative effectiveness analysis, we found a significantly lower ARR for patients starting natalizumab compared with fingolimod (rate ratio [RR] = 0.65; 95% confidence interval [CI], 0.57-0.73) or BRACETD (RR = 0.46; 95% CI, 0.42-0.53). Similarly, CDI6M was higher for patients starting natalizumab compared with fingolimod (hazard ratio [HR] = 1.25; 95% CI, 1.01-1.55) and BRACETD (HR = 1.46; 95% CI, 1.16-1.85). In patients starting fingolimod, we found a lower ARR (RR = 0.72; 95% CI, 0.65-0.80) compared with starting BRACETD, but no difference in CDI6M (HR = 1.17; 95% CI, 0.91-1.50). Differences in CDW6M were not found between the treatment groups. In the base-case cost-effectiveness analysis, natalizumab dominated fingolimod (0.302 higher quality-adjusted life-years [QALYs] and £17,141 lower predicted lifetime costs). Similar cost-effectiveness results were observed across sensitivity analyses. CONCLUSIONS: This MSBase Registry analysis suggests that natalizumab improves clinical outcomes when compared with fingolimod, which translates to higher QALYs and lower costs in UK patients with RES-RRMS.

There are several medications used to treat people with relapsing remitting multiple sclerosis, such as interferon-based therapies (Betaferon/Betaseron (US), Rebif, Avonex, Extavia), glatiramer acetate (Copaxone), teriflunomide (Aubagio), and dimethyl fumarate (Tecfidera), collectively named BRACETD. Other treatments for multiple sclerosis (MS) have a narrower use, such as natalizumab (Tysabri) or fingolimod (Gilenya), among others.This study objective was to assess how well natalizumab and fingolimod helped treating MS (clinical effectiveness) and subsequently estimate what the cost of these treatments is in comparison to the benefit they bring to people with rapidly evolving severe MS that use them in the United Kingdom (UK) (cost-effectiveness).We used an international disease registry (MSBase), which collects clinical data from people with MS in various centers around the world to compare the effectiveness of natalizumab, fingolimod and BRACETD treatments. We used a technique called propensity score matching to obtain results from comparable patient groups. People treated with natalizumab had better disease control, namely with fewer relapses and higher improvement on their disability level, than patients on fingolimod or BRACETD. Conversely, there were no differences between each group of people on a measure called disability worsening.Based on these clinical results, we built an economic model that simulates the lifetime costs and consequences of treating people with MS with natalizumab in comparison with fingolimod. We found that using natalizumab was less costly and was more effective compared to using fingolimod in UK patients.

Textbook outcome in colon carcinoma: implications for overall survival and disease-free survival.

BACKGROUND: Textbook outcome (TO) is a multidimensional quality management tool that uses a set of traditional surgical measures to reflect an "ideal" surgical result for a particular pathology. The aim of the present study is to record the rate of TO in patients undergoing elective surgery for colon cancer (CC). MATERIAL AND METHODS: Retrospective study of all patients undergoing scheduled CC surgery at a Spanish university hospital from September 2012 to August 2016. Patients with rectal cancer were excluded. The variables included in the definition of TO were: R0 resection, number of isolated nodes ≥ 12, no Clavien-Dindo ≥ IIIa complications, no prolonged stay, no readmissions, and no mortality in the first 30 days. The main objective of this study is to analyse the achievement of TO in these patients and to assess the relationship between TO and overall and disease-free survival. RESULTS: Five hundred and sixty-four patients were included in the study. TO was achieved in 49.8%. The sample had a mean age of 69 ± 11 years, and 60% were male. Female sex (OR 1.61; 95% CI 2.30-1.13), T3 and T4 classification (OR 2.50, 95% CI 4.59-1.36, and OR 2.55, 95% CI 5.21-1.24 respectively) and laparoscopic approach (OR 1.53, 95% CI 2.33-1.00) were independent factors that were significantly associated with achieving a TO. Patients who achieved TO had higher overall survival (p = 0.008) than those who did not. However, with regard to disease-free survival, no statistically significant differences were found (p = 0.303). CONCLUSION: TO is a useful, easy-to-interpret management tool for measuring oncological results and for predicting patient survival.

Diagnóstico y evolución de los pacientes con derrames pleurales idiopáticos / Diagnosis and outcome of patients with idiopathic pleural effusions

Introducción No se ha determinado la evolución de los pacientes con derrames pleurales idiopáticos con un seguimiento a largo plazo. Métodos Entre octubre de 2013 y junio de 2021 se hizo un seguimiento prospectivo de todos los pacientes con derrame idiopático mediante exploración clínica y estudios de imagen al cabo de 1, 3 y seis meses y cada seis meses durante un mínimo de un año. Resultados Veintinueve pacientes fueron diagnosticados de derrame idiopático y objeto de seguimiento. Durante el seguimiento se detectó un mesotelioma en dos pacientes al cabo de siete y 18 meses; en uno de ellos se observó líquido pleural teñido de sangre y el otro refirió una pérdida de peso de 10%. En ninguno de los pacientes con derrame que cubriera menos de dos tercios del hemitórax y sin síntomas constitucionales ni aparición de líquido teñido de sangre se diagnosticó un mesotelioma. La mayoría de los derrames desaparecieron o mostraron una clara mejoría en los primeros seis meses. Conclusiones Los pacientes sin pérdida de peso y con derrames no hemáticos pequeños pueden beneficiarse de un tratamiento conservador y un seguimiento clínico-radiológico (AU)

Introduction Long-term follow-up course for patients with idiopathic pleural effusions has not been established. Methods From October 2013 to June 2021 all patients with idiopathic effusion were prospectively followed up with clinical examination and imaging at 1,3,6 and every 6 months for a minimum of 1 year. Results Twenty-nine patients were diagnosed with idiopathic effusion and followed up. Mesothelioma was detected during the follow-up in two patients at 7 and 18 months, one of whom had blood-tinged pleural fluid and the other reported a 10% weight loss. Mesothelioma was not diagnosed in any of the patients with effusion covering less than two thirds of the hemithorax, and without constitutional symptoms or a blood-tinged fluid appearance. Most of the effusions resolved or showed a clear improvement in the first six months. Conclusions Patients without weight loss and with small, non-hematic effusions, may benefit from conservative treatment and clinical-radiological follow-up (AU)

Diagnosis and outcome of patients with idiopathic pleural effusions.

INTRODUCTION: Long-term follow-up course for patients with idiopathic pleural effusions has not been established. METHODS: From October 2013 to June 2021 all patients with idiopathic effusion were prospectively followed up with clinical examination and imaging at 1, 3, 6 and every 6 months for a minimum of 1 year. RESULTS: Twenty-nine patients were diagnosed with idiopathic effusion and followed up. Mesothelioma was detected during the follow-up in two patients at 7 and 18 months, one of whom had blood-tinged pleural fluid and the other reported a 10% weight loss. Mesothelioma was not diagnosed in any of the patients with effusion covering less than two thirds of the hemithorax, and without constitutional symptoms or a blood-tinged fluid appearance. Most of the effusions resolved or showed a clear improvement in the first six months. CONCLUSION: Patients without weight loss and with small, non-hematic effusions, may benefit from conservative treatment and clinical-radiological follow-up.

Hemophilia and non-accidental head trauma in two siblings: lessons and legal implications.

Non-accidental head trauma (NAHT) is a common cause of traumatic brain injury in childhood, origin of profound and disabling neurological sequalae, and in the most disgraceful cases, ultimately death.Subdural hematoma (SDH) is the most common intracranial finding in NAHT. On the other hand, congenital bleeding disorders are a minor but a significant cause of ICH in the neonate and toddler. Not uncommonly, intracranial bleeding is the first sign of a severe inherited coagulation disorder. In the presence of an unexpected intracranial bleeding after a minor trauma or without a clear history of the related events, physicians and caregivers may be confronted to the dilemma of a possible child abuse. It must be bear in mind that physical abuse and bleeding disorders can co-exist in the same child.We report here the case of two siblings in whom a diagnosis of hemophilia coexisted with the presumption of a non-accidental head trauma. Child abuses were inflicted in both children with a spare time of 2 years. A diagnosis of mild hemophilia was prompted in the first sibling after initial NAHT, while inflicted trauma was evident in the second sibling after neuroimaging findings and concomitant lesions. Lessons from this case in co-existing bleeding disorders and inflicted trauma and legal implications derived will be discussed thereafter.The possibility of a bleeding disorder should be considered in all children presenting with unexplained bleeding at a critical site in the setting of suspected physical maltreatment, particularly intracranial hemorrhage (ICH).

Validation and comparison of Breast Graded Prognostic Assessment scores in patients with breast cancer and brain metastases.

PURPOSE: Brain metastases (BM) occur in 15-35% of patients with metastatic breast cancer, conferring poor prognosis and impairing quality of life. Clinical scores have been developed to classify patients according to their prognosis. We aimed to check the utility of the Breast Graded Prognostic Assessment (B-GPA) and its modified version (mB-GPA) and compare them in routine clinical practice. METHODS: This is an ambispective study including all patients with breast cancer BM treated in a single cancer comprehensive center. We analyzed the overall survival (OS) from BM diagnosis until death. The Kaplan-Meier method and Cox proportional hazard regression model were used in the analyses. ROC curves were performed to compare both scores. RESULTS: We included 169 patients; median age was 50 years. HER2-positive and triple negative patients were 33.7% and 20.7%, respectively. At the last follow-up, 90% of the patients had died. Median OS was 12 months (95% confidence interval 8.0-16.0 months). OS was worse in patients with > 3 BM and in patients with triple negative subtype. CONCLUSIONS: In our series, we confirm that B-GPA and mB-GPA scores correlated with prognosis. ROC curves showed that B-GPA and mB-GPA have similar prognostic capabilities, slightly in favor of mB-GPA.

A population-based epidemiological study of neuromyelitis optica spectrum disorder in Hungary.

BACKGROUND AND PURPOSE: The goal of this study was to determine the prevalence and incidence of neuromyelitis optica spectrum disorder (NMOSD) in Hungary based on the 2015 International Panel of NMO Diagnosis (IPND) criteria. METHODS: A retrospective population-based cohort study was conducted of 6.4 million Hungarians (age ≥ 16 years) between 1 January 2006 and 31 December 2016. Possible NMOSD patients were selected via multistage re-evaluation from multiple sources. Crude and sex- and serostatus-specific prevalence (per 100 000 persons) and incidence rates (per 1 000 000 person-years) from 2006 to 2015 were estimated and age-adjusted rates were determined. RESULTS: Of 2262 study candidates, 154 NMOSD patients (age ≥ 16 years) with onset until 31 December 2016 were identified based on 2015 IPND criteria. The prevalence analysis on 1 January 2016 included 123 NMOSD living cases, resulting in a prevalence of 1.91 [95% confidence interval (CI) 1.52-2.28] per 100 000 persons. The 101 incident cases emerging from the observed 76 394 288 person-years provided an incidence rate of 1.32 (95% CI 1.08-1.61) per 1 000 000 person-years. Age-adjusted prevalence was 1.87 (95% CI 1.56-2.23) per 100 000 persons and incidence was 1.20 (95% CI 0.98-1.46) per 1 000 000 person-years. CONCLUSIONS: In this first report of a large population-based epidemiological study from an Eastern European Caucasian population using robust case validation, a greater prevalence and incidence of NMOSD was found compared to previous large studies in Caucasian populations.

[Radiation-induced cognitive toxicity in adults]. / Neurotoxicidad cognitiva inducida por la radioterapia cerebral en adultos.

Cognitive toxicity induced by cranial radiation is one of the most important limitations of radiation therapy and has a significant impact on brain tumor survivors' quality of life. This review comprehends an up to date of recent studies including complete neuropsychological battery and/or advanced neuroimaging techniques. These studies identified critical anatomical and/or functional brain areas related to radiation-induced brain injury, thus improving clinical and radiological diagnosis. Pathophysiological mechanisms underlying cognitive toxicity are complex and involve different cell lines and molecules. Although there is no currently therapeutic strategy that has a demonstrated efficacy, several studies including sparing of hippocampus or the use of memantine are quite promising. A better knowledge of the characteristics of cognitive toxicity induced by cranial radiation, will help us to identify patients who will benefit from treatment and also to examine new therapeutic targets in order to improve patients' quality of life.

TITLE: Neurotoxicidad cognitiva inducida por la radioterapia cerebral en adultos.La toxicidad cognitiva inducida por la radioterapia craneal es una de las limitaciones mas importantes del tratamiento radioterapico y con mas impacto sobre la calidad de vida de los largos supervivientes de tumores cerebrales. Esta revision incluye una actualizacion del diagnostico clinico y radiologico de la toxicidad radioinducida con la incorporacion de baterias neuropsicologicas y tecnicas avanzadas en neuroimagen. Ambas herramientas han permitido en los ultimos años no solo una mejor definicion de la disfuncion cognitiva, sino tambien la identificacion de los cambios anatomicos y funcionales asociados. La fisiopatologia subyacente implica diferentes estirpes celulares y vias de señalizacion molecular, y el mecanismo es multifactorial. Aunque no existe actualmente una estrategia terapeutica que haya demostrado una clara eficacia, varios estudios, incluyendo los que proponen respetar el hipocampo o el uso de la memantina, han resultado prometedores. Profundizar en el estudio de la toxicidad cognitiva inducida por la radioterapia permitira definir mejor los pacientes que se benefician de la radioterapia, asi como estudiar nuevas dianas terapeuticas para mejorar la calidad de vida de los pacientes con daño cerebral radioinducido.

Performance monitoring in lung cancer patients pre- and post-chemotherapy using fine-grained electrophysiological measures.

No previous event-related potentials (ERPs) study has explored the error-related negativity (ERN) - an ERP component indexing performance monitoring - associated to cancer and chemotherapy-induced cognitive impairment in a lung cancer population. The aim of this study was to examine differences in performance monitoring in a small-cell lung cancer group (SCLC, C +) 1-month following chemotherapy and two control groups: a non-small cell lung cancer patient group (NSCLC, C -) prior to chemotherapy and a healthy control group (HC). Seventeen SCLC (C +) underwent a neuropsychological assessment and an ERP study using a flanker and a stop-signal paradigm. This group was compared to fifteen age-, gender- and education-matched NSCLC (C -) and eighteen HC. Between 20 and 30% of patients in both lung cancer groups (C + and C -) met criteria for cognitive impairment. Concerning ERPs, lung cancer patients showed lower overall hit rate and a severe ERN amplitude reduction compared to HC. Lung cancer patients exhibited an abnormal pattern of performance monitoring thus suggesting that chemotherapy and especially cancer itself, may contribute to cognitive deterioration. ERN appeared as an objective laboratory tool sensitive to cognitive dysfunction in cancer population.

Long-term impact of temozolomide on 1p/19q-codeleted low-grade glioma growth kinetics.

Although upfront temozolomide (TMZ) has been widely-used to treat 1p/19q-codeleted diffuse low-grade gliomas (LGG), its long-term impact on the growth kinetics of these tumors has not been determined. Based on serial magnetic resonance images we retrospectively evaluated the evolution of the mean tumor diameter (MTD) in 36 progressive 1p/19q-codeleted LGG treated with upfront TMZ. After TMZ onset, all but two patients (94.4%) presented a progressive MTD decrease that lasted for a median duration of 23 months (range 3-114). In 10 patients (27%) MTD regrowth occurred during TMZ treatment and in 22 patients (66%) after TMZ discontinuation. In these patients, median time to MTD regrowth after TMZ discontinuation was 12 months (range 1-88). The rate of MTD regrowth at 3 and 5 years after TMZ onset was 77 and 94%, respectively. Time to tumor progression (TTP) based on volumetric analysis was shorter than TTP based on Response Assessment in Neuro-Oncology (RANO) bidimensional criteria (23 vs. 35 months, p = 0.05) and shorter than time to next oncological treatment (23 vs. 46 months, p = 0.001). In 10 patients (27%), absence of volumetric analysis led to continue TMZ for a median of 10 cycles after MTD had started to regrow. Volumetric analysis is important to precisely assess chemotherapy efficacy in 1p/19q-codeleted LGG, identify early tumor progression and avoid futile chemotherapy continuation. In the present series, although some long-lasting volumetric responses were observed, most tumors resumed their growth within 3 years after TMZ onset.

Brain functional connectivity in lung cancer population: an exploratory study.

The present study aimed to explore the functional connectivity differences in Resting State Networks (RSNs) induced by cancer and chemotherapy in Lung Cancer (LC) patients using an Independent Component Analysis (ICA). Three matched groups of 15 LC patients following Chemotherapy (C+), 15 LC patients before Chemotherapy (C-) and 15 Healthy Controls (HC) were included. Analysis was performed using ICA and a multivariate pattern analysis (MVPA) to classify groups based on profiles of functional connectivity. We found significant differences in four of the RSN identified: Default Mode Network (DMN), Predominantly Left and Right Anterior Temporal Network, and Cerebellum Network. Whereas DMN showed decreased connectivity, the other RSNs exhibited increased connectivity in both LC groups compared to HC and in C+ in comparison to C-. MVPA discriminated significantly and accurately between all groups. Our study showed that disrupted functional connectivity associated with cancer and chemotherapy-induced cognitive deficits is not only related to DMN decreased connectivity abnormalities but also to an increased connectivity of other RSNs, suggesting a potential compensatory mechanism. Graphical abstract.

Seizure-susceptible brain regions in glioblastoma: identification of patients at risk.

BACKGROUND AND PURPOSE: The main aim of this study was to identify which patients with glioblastoma multiforme (GBM) have a higher risk of presenting seizures during follow-up. METHODS: Patients with newly diagnosed GBM were reviewed (n = 306) and classified as patients with (Group 1) and without (Group 2) seizures at onset. Group 2 was split into patients with seizures during follow-up (Group 2A) and patients who never had seizures (Group 2B). The anatomical location of GBM was identified and compared by voxel-based lesion symptom mapping (discovery set). Seizure-susceptible brain regions obtained were assessed visually and automatically in external GBM validation series (n = 85). RESULTS: In patients with GBM who had no seizures at onset, an increased risk of presenting seizures during follow-up was identified in the superior frontal and inferior occipital lobe, as well as in inferoposterior regions of the temporal lobe. Conversely, those patients with GBM located in medial and inferoanterior temporal areas had a significantly lower risk of suffering from seizures during follow-up. Additionally, the seizure-susceptible brain region maps obtained classified patients in the validation set with high positive and negative predictive values. CONCLUSIONS: Tumor location is a useful marker to identify patients with GBM who are at risk of suffering from seizures during follow-up. These results may help to support the use of antiepileptic prophylaxis in a selected GBM population and to improve stratification in antiepileptic clinical trials.

First report of the novel atypical porcine pestivirus in Spain and a retrospective study.

This study aimed to provide information regarding viral pathogenesis and molecular epidemiology linked with recently reported atypical porcine pestivirus (APPV) strains and to determine the circulation of APPV in Spain from 1997 to 2016. Two-day-old piglets with moderate-severe congenital tremor (CT) from a Spanish farm were received for diagnostic purposes. Sera, nasal and rectal swabs and tissue samples were collected. qRT-PCR was performed in these samples, and a retrospective study to detect APPV RNA was carried out using a serum collection from 1997 to 2016. APPV genome was identified with high and moderate RNA loads in different tissues of the CT affected pigs. High APPV RNA load was detected in lymphoid organs, suggesting that these constitute a target for APPV replication. In 89 of the 642 retrospectively analysed samples (13.9%), APPV genome was detected. CT cases were related to the presence of APPV in viraemic piglets below 1 week of age, in which the viral RNA load was the highest. A considerable number of animals between 4 and 14 weeks of age and some 1-week-old piglets were viraemic in the absence of CT, which can act as carriers of the virus. The relative risk of APPV and CT was 8.5 (CI 95% 5.8-12.5). Thus, our data show that APPV infection is epidemiologically related to CT. Phylogenetic analysis from 1615 NS2-3 nucleotides showed only one defined APPV clade, grouping the most phylogenetically related strains from Europe and China. Of this clade, there are other strains from Europe, USA and China. This data confirm the high APPV genetic diversity, not being able to cluster this virus according to the geographic area. Our result showed that APPV has been circulating in Spain at least since 1997, being the earliest date of detection of this virus worldwide and suggesting that APPV may be widespread.

Post-Natal Persistent Infection With Classical Swine Fever Virus in Wild Boar: A Strategy for Viral Maintenance?

In this study, fifteen wild boar piglets were intranasally inoculated <10 h after birth with the moderately virulent classical swine fever virus (CSFV) strain Catalonia 01. At 5 days post-inoculation, seven other animals within 48 h of birth were put in contact with them. Viral replication and innate and specific immune responses were evaluated. Of the inoculated animals, 46.67% remained post-natally persistently infected and were apparently healthy with neither humoral nor cellular immunological responses specific to CSFV and with high viral loads in their blood, organs and body secretions. Moreover, the present data extend the time period to 48 h after birth when a moderately virulent CSFV strain could lead to post-natal persistent infection given the generation of persistently infected wild boars in the contact group (33.33%). The innate immune response to the virus, as measured by type I IFN-α in serum, was mostly not impaired in the persistently infected wild boars. Interestingly, a decrease and lack of IFN-γ-producing cells against CSFV and PHA was observed. In endemic countries where wild swine species are increasing and low and moderate virulence CSFV strains are prevalent, the possible generation of this form of disease cannot be ruled out.

Estudio comparativo en la definición del volumen de tratamiento en radioterapia con «Slow TC Scan» vs. 4D PET/TC Scan en estadios iniciales de cáncer de pulmón de célula no pequeña / A comparative study of the target volume definition in radiotherapy with «Slow CT Scan» vs. 4D PET/CT Scan in early stages non-small cell lung cancer

Objetivos. Evaluar el uso de la 4D PET/TC para capturar el movimiento respiratorio en comparación con la «slow»-TC (TCs), en el procedimiento de planificación de radioterapia. Material y métodos. Se ha incluido a 25 pacientes diagnosticados de estadio inicial de cáncer de pulmón de célula no pequeña (NSCLC) médicamente inoperable. A cada paciente se le realizó una TCs (4 s/corte) y una 4D PET/TC. La idoneidad de cada técnica en la captura del movimiento respiratorio fue evaluada comparando el volumen definido por cada una de ellas: internal target volumen (ITV) 4D y el ITVslow, con relación a la suma de los volúmenes de la 4D PET/TC y la TCs (ITVsuma). La máxima diferencia entre el volumen definido por cada técnica respecto al volumen suma fue evaluada en una proyección antero-posterior y otra lateral. Resultados. Los volúmenes generados con 4D PET/TC consiguen una definición más precisa del ITV que los volúmenes obtenidos con TCs (ITV4D/ITVsuma 78% vs. ITVslow/ITVsuma 63%). En general, los volúmenes de la 4D PET/TC son de mayor tamaño (19,9 vs. 16,3 cc). El ITV4D muestra menor diferencia con el ITVsuma en los ejes cráneo-caudal y antero-posterior respecto al ITVslow y capta el movimiento de forma más exacta. La máxima diferencia observada es de 0,36mm en la 4D PET/TC y de 0,57mm en la TCs en el eje antero-posterior. Conclusiones. La planificación con 4D PET/TC en comparación con TCs permite cuantificar el movimiento respiratorio del tumor y mejorar la planificación de radioterapia en estadios iniciales de NSCLC (AU)

Objectives. To evaluate the use of 4D PET/CT to quantify tumor respiratory motion compared to the «Slow»-CT (CTs) in the radiotherapy planning process. Material and methods. A total of 25 patients with inoperable early stage non small cell lung cancer (NSCLC) were included in the study. Each patient was imaged with a CTs (4s/slice) and 4D PET/CT. The adequacy of each technique for respiratory motion capture was evaluated using the volume definition for each of the following: Internal target volume (ITV) 4D and ITVslow in relation with the volume defined by the encompassing volume of 4D PET/CT and CTs (ITVtotal). The maximum distance between the edges of the volume defined by each technique to that of the total volume was measured in orthogonal beam's eye view. Results. The ITV4D showed less differences in relation with the ITVtotal in both the cranio-caudal and the antero-posterior axis compared to the ITVslow. The maximum differences were 0.36mm in 4D PET/CTand 0.57mm in CTs in the antero-posterior axis. 4D PET/CT resulted in the definition of more accurate (ITV4D/ITVtotal 0.78 vs. ITVs/ITVtotal 0.63), and larger ITVs (19.9 cc vs. 16.3 cc) than those obtained with CTs. Conclusion. Planning with 4D PET/CT in comparison with CTs, allows incorporating tumor respiratory motion and improving planning radiotherapy of patients in early stages of lung cancer (AU)

Recommendations of «not-to-do¼: Proposals of the Spanish Association of Surgeons to the project «Commitment to quality of scientific societies¼ / Recomendaciones de «no hacer¼: propuestas de la Asociación Española de Cirujanos al proyecto de «Compromiso por la calidad de las sociedades científicas¼

"INTRODUCTION: The initiative of the Spanish Ministry of Health «Commitment to quality of scientific societies¼, aims to reduce unnecessary interventions of healthcare professionals. METHODS: The Spanish Association of Surgeons has selected 22 experts from the different sections that have participated in the identification of 26 proposals «do not do¼ to be ordered by the expected impact its implementation would have according to the GRADE methodology. From these proposals, the Delphi technique was used to select 5 recommendations presented in more detail in this article. RESULTS: The 5 selected recommendations are: Do not perform cholecystectomy in patients with asymptomatic cholelithiasis; do not keep bladder catheterization more than 48hours; do not extend antibiotic prophylaxis treatments more than 24hours after a surgical procedure; do not perform routine antibiotic prophylaxis for uncomplicated clean and no prosthetic surgery; and do not use antibiotics postoperatively after uncomplicated appendicitis. CONCLUSION: The Spanish Association of Surgeons's participation in this campaign has allowed a reflection on those activities that do not add value in the field of surgery and it is expected that the spread of this process serves to reduce its performance."

"Introducción La iniciativa del Ministerio de Sanidad «Compromiso por la calidad de las sociedades científicas¼ tiene como objetivo disminuir las intervenciones innecesarias de los profesionales sanitarios. Métodos La Asociación Española de Cirujanos ha seleccionado a 22 expertos de las diferentes secciones que han participado en la identificación de 26 propuestas de «no hacer¼ que se ordenaron por el impacto esperado que tendría su puesta en marcha según la metodología GRADE. A partir de estas propuestas, se ha utilizado una técnica de Delphi para seleccionar las 5 recomendaciones más importantes en relación con el impacto potencial que tendría su aplicación. Resultados Las 5 recomendaciones seleccionadas son: no realizar colecistectomía en pacientes con colelitiasis asintomática; no mantener sondaje vesical más de 48 h; no prolongar más de 24 h, tras un procedimiento quirúrgico, los tratamientos de profilaxis antibiótica; no realizar profilaxis antibiótica de rutina para la cirugía no protésica limpia y no complicada, y no emplear tratamiento antibiótico postoperatorio tras apendicitis no complicada. Conclusión La participación de la Asociación Española de Cirujanos en esta campaña ha permitido una reflexión sobre aquellas actuaciones que no aportan valor en el ámbito de nuestra especialidad y es esperable que la difusión de este proceso sirva para reducir su realización."

Bloodstream infections caused by Escherichia coli producing AmpC ß-lactamases: epidemiology and clinical features.

The aim of the study was to investigate the epidemiology and clinical features of bloodstream infections due to Escherichia coli producing AmpC ß-lactamases (AmpC-Ec-BSI). In a multi-centre case-control study, all third-generation-cephalosporin-resistant Escherichia coli BSI (3GC-Ec-BSI) isolates were analysed. Acquired bla AmpC (bla ac-AmpC) detection was done by polymerase chain reaction (PCR) and sequencing. Chromosomal bla AmpC (bla c-AmpC) expression was quantified by real-time PCR. Cases were patients with AmpC-Ec-BSI. Controls were patients with cephalosporin-susceptible E. coli BSI, matched 1:1 by sex and age. Demographics, comorbidities, intrinsic and extrinsic risk factors for antimicrobial resistance, clinical presentation and outcomes were investigated. Among 841 E. coli BSI, 17 were caused by AmpC-Ec (2 %). Eleven isolates (58.8 %) had bla ac-AmpC and six were bla c-AmpC overproducers. The mean age of cases was 66.2 years and 71 % were men. Cases were more frequently healthcare-related (82 vs. 52 % controls, p < 0.05) and presented more intrinsic and extrinsic risk factors. At least one risk factor was present in 94.1 % of cases vs. 41.7 % of controls (p = 0.002). Severity and length of stay (LOS) were higher among cases (mean Pitt Score 2.6 vs. 0.38 in controls, p = 0.03; LOS 17.5 days vs. 6 in controls, p = 0.02). Inappropriate empirical therapy (IET) was administered to 70.6 % of cases and 23.5 % of controls (p < 0.003). No differences were found in terms of cure rate at the 14th day and mortality. Bloodstream infections due to AmpC-Ec (mostly plasmid-mediated) are infrequent in our area. AmpC-Ec-BSI affects mainly patients with intrinsic risk factors and those with previous antibiotic exposure. A high proportion received IET.

A comparative study of the target volume definition in radiotherapy with «Slow CT Scan¼ vs. 4D PET/CT Scan in early stages non-small cell lung cancer. / Estudio comparativo en la definición del volumen de tratamiento en radioterapia con «Slow TC Scan¼ vs. 4D PET/TC Scan en estadios iniciales de cáncer de pulmón de célula no pequeña.

OBJECTIVES: To evaluate the use of 4D PET/CT to quantify tumor respiratory motion compared to the «Slow¼-CT (CTs) in the radiotherapy planning process. MATERIAL AND METHODS: A total of 25 patients with inoperable early stage non small cell lung cancer (NSCLC) were included in the study. Each patient was imaged with a CTs (4s/slice) and 4D PET/CT. The adequacy of each technique for respiratory motion capture was evaluated using the volume definition for each of the following: Internal target volume (ITV) 4D and ITVslow in relation with the volume defined by the encompassing volume of 4D PET/CT and CTs (ITVtotal). The maximum distance between the edges of the volume defined by each technique to that of the total volume was measured in orthogonal beam's eye view. RESULTS: The ITV4D showed less differences in relation with the ITVtotal in both the cranio-caudal and the antero-posterior axis compared to the ITVslow. The maximum differences were 0.36mm in 4D PET/CTand 0.57mm in CTs in the antero-posterior axis. 4D PET/CT resulted in the definition of more accurate (ITV4D/ITVtotal 0.78 vs. ITVs/ITVtotal 0.63), and larger ITVs (19.9 cc vs. 16.3 cc) than those obtained with CTs. CONCLUSION: Planning with 4D PET/CT in comparison with CTs, allows incorporating tumor respiratory motion and improving planning radiotherapy of patients in early stages of lung cancer.

Prediction of anastomotic leak in colorectal cancer surgery based on a new prognostic index PROCOLE (prognostic colorectal leakage) developed from the meta-analysis of observational studies of risk factors.

PURPOSE: To obtain a prognostic index, which has been named PROCOLE (prognostic colorectal leakage), it can predict the risk that a certain individual may suffer anastomotic leakage. METHODS: The methodology consists of a systematic review to identify potential risk factors for anastomotic leakage and a meta-analysis of studies of each of these factors. In the meta-analysis, the prognostic index integrates factors that are statistically significant, which are weighted according to the estimated value of the effect size. The prognostic index was validated using retrospectively collected data from patients who underwent colorectal cancer surgery anastomosis at our institution. RESULTS: The mean and standard deviation of the PROCOLE prognostic index in patients with anastomotic leakage is 1.9 ± 6.13, whereas in controls, it is 3.63 ± 2.1. The predictive ability of the PROCOLE, assessed by calculating the area under the curve (AUC) of the receiver operating characteristic (ROC), results in an AUC of 0.82 with a 95% confidence interval (CI) (0.75, 0.89) of the AUC, and it can be considered a good prognostic indicator. CONCLUSIONS: The PROCOLE prognostic index predicts the risk of a certain individual developing anastomotic leakage after colorectal cancer surgery. Specifically, the PROCOLE prognostic index establishes a discrimination value threshold of 4.83 for recommending the implementation of a protective stoma. We have developed free software with a simple interface that only requires the selection of risk factors to obtain the PROCOLE value.