Safety and effectiveness of direct-acting antiviral drugs in the treatment of hepatitis C in patients with inflammatory bowel disease.

BACKGROUND AND AIMS: Hepatitis C virus (HCV) management in Inflammatory Bowel Disease (IBD) is uncertain. The ECCO guidelines 2021 recommended HCV treatment but warn about the risk of IBD reactivation. We aimed to evaluate 1) the effectiveness and safety of direct-acting antivirals (DAAs) in IBD; 2) the interaction of DAAs with IBD drugs. METHODS: Multicentre study of IBD patients and HCV treated with DAAs. Variables related to liver diseases and IBD, as well as adverse events (AEs) and drug interactions, were recorded. McNemar's test was used to assess differences in the proportion of active IBD during the study period. RESULTS: We included 79 patients with IBD and HCV treated with DAAs from 25,998 IBD patients of the ENEIDA registry. Thirty-one (39.2 %) received immunomodulators/biologics. There were no significant differences in the percentage of active IBD at the beginning (n = 11, 13.9 %) or at the 12-week follow-up after DAAs (n = 15, 19 %) (p = 0.424). Sustained viral response occurred in 96.2 % (n = 76). A total of 8 (10.1 %) AEs occurred and these were unrelated to activity, type of IBD, liver fibrosis, immunosuppressants/biologics, and DAAs. CONCLUSIONS: We demonstrate a high efficacy and safety of DAAs in patients with IBD and HCV irrespective of activity and treatment of IBD.

A focus on the multiple interfaces between action and perception and their neural correlates.

Successful behaviour relies on the appropriate interplay between action and perception. The well-established dorsal and ventral stream theories depicted two distinct functional pathways for the processes of action and perception, respectively. In physiological conditions, the two pathways closely cooperate in order to produce successful adaptive behaviour. As the coupling between perception and action exists, this requires an interface that is responsible for a common reading of the two functions. Several studies have proposed different types of perception and action interfaces, suggesting their role in the creation of the shared interaction channel. In the present review, we describe three possible perception and action interfaces: i) the motor code, including common coding approaches, ii) attention, and iii) object affordance; we highlight their potential neural correlates. From this overview, a recurrent neural substrate that underlies all these interface functions appears to be crucial: the parieto-frontal circuit. This network is involved in the mirror mechanism which underlies the perception and action interfaces identified as common coding and motor code theories. The same network is also involved in the spotlight of attention and in the encoding of potential action towards objects; these are manifested in the perception and action interfaces for common attention and object affordance, respectively. Within this framework, most studies were dedicated to the description of the role of the inferior parietal lobule; growing evidence, however, suggests that the superior parietal lobule also plays a crucial role in the interplay between action and perception. The present review proposes a novel model that is inclusive of the superior parietal regions and their relative contribution to the different action and perception interfaces.

Validation of Visual Analogue Scale for loss of smell as a quick test in chronic rhinosinusitis with nasal polyps.

BACKGROUND AND OBJECTIVE: Diagnostic criteria of chronic rhinosinusitis with nasal polyps (CRSwNP) include, among others, olfactory dysfunction (OD). We hypothesize that patients suffering with CRSwNP are good at self-assessing their sense of smell through visual analogue scale (VAS) compared to smell tests. METHODS: A controlled cross-sectional study was planned. Adults diagnosed with severe CRSwNP waiting for endoscopic sinus surgery were included. A cohort of healthy controls was also studied. All participants performed Barcelona smell test (BAST-24), sinonasal outcomes test 22 (SNOT-22), and VAS for loss of smell. CRSwNP underwent blood test (eosinophils count, total serum IgE), CT scan (Lund-Mackay Score), and nasal endoscopy. RESULTS: 138 severe CRSwNP and 40 controls subjects were included. The BAST-24 identification score was strongly correlated with the VAS score in the CRSwNP group (rho=-0.79, p<0.001) but not in the control group (rho=-0.14; p=0.39), this difference between groups being statistically significant (p<0.001). A significant correlation of SNOT-22 item 21 (loss of smell) was also found with BAST-24 identification (rho=-0.65, p<0.001), this difference being statistically significant (Z=-2.43; p=0.015). In the ROC curve, the area under the curve (AUC) was 0.85 with 72.5% sensitivity and 93.1% specificity. CONCLUSION: This study demonstrates a potential role of the VAS score for the screening of OD in severe CRSwNP in daily clinical practice.

UK 2022 Consensus on Normal Tissue Dose-Volume Constraints for Oligometastatic, Primary Lung and Hepatocellular Carcinoma Stereotactic Ablative Radiotherapy.

The use of stereotactic ablative radiotherapy (SABR) in the UK has expanded over the past decade, in part as the result of several UK clinical trials and a recent NHS England Commissioning through Evaluation programme. A UK SABR Consortium consensus for normal tissue constraints for SABR was published in 2017, based on the existing literature at the time. The published literature regarding SABR has increased in volume over the past 5 years and multiple UK centres are currently working to develop new SABR services. A review and update of the previous consensus is therefore appropriate and timely. It is hoped that this document will provide a useful resource to facilitate safe and consistent SABR practice.

Prognostic implications of Anemia in patients with acute heart failure in emergency departments. ANEM-AHF Study.

INTRODUCTION: The presence of anaemia leads to a worse prognosis in patients with heart failure (HF). There are few data on the impact of anaemia on mortality in patients with acute heart failure (AHF), and the studies available are mainly retrospective, and include hospitalised patients. OBJECTIVE: Evaluate the role of anaemia on 30-day and 1-year mortality in patients with AHF attended in hospital emergency departments (HEDs). METHODS: We performed a multicentre, observational study of prospective cohorts of patients with AHF. The study variables were: Anaemia (haemoglobin < 12g/dL in women and <13g/dL in men), mortality at 30 days and at 1 year, risk factors, comorbidity, functional impairment, basal functional grade for dyspnoea, chronic and acute treatment, clinical and analytical data of the episode, and patient destination. STATISTICAL ANALYSIS: Bivariate analysis and survival analyses using Cox regression. RESULTS: A total of 13 454 patients were included, 7662 (56.9%) of whom had anaemia. Those with anaemia were older, had more comorbidity, a worse functional status and New York Heart Association class, greater renal function impairment, and more hyponatraemia. The mortality was higher in patients with anaemia at 30 days and 1 year: 7.5% vs 10.7% (P < .001) and 21.2% vs 31.4% (P < .001), respectively. The crude and adjusted hazard ratios of anaemia for 30-day mortality were: 1.46 (confidence interval [CI] 95% 1.30-1.64); P < .001 and 1.20 (CI 95% 1.05-1.38); P = .009, respectively, and 1.57 (CI 95% 1.47-1.68) and 1.30 (CI 95% 1.20-1.40) for mortality at 1 year. The weight of anaemia on mortality was different in each follow-up period. CONCLUSIONS: Anaemia is an independent predictor of mortality at 30 days and 1 year in patients with AHF attended in HEDs. It is important to study the aetiology of AHF since adequate treatment would reduce mortality.

Combined effects of land-use intensification and plant invasion on native communities.

Land-use intensification (LUI) and biological invasions are two of the most important global change pressures driving biodiversity loss. However, their combined impacts on biological communities have been seldom explored, which may result in misleading ecological assessments or mitigation actions. Based on an extensive field survey of 445 paired invaded and control plots of coastal vegetation in SW Spain, we explored the joint effects of LUI (agricultural and urban intensification) and invasion on the taxonomic and functional richness, mean plant height and leaf area of native plants. Our survey covered five invasive species with contrasting functional similarity and competitive ability in relation to the native community. We modeled the response of native communities for the overall and invader-specific datasets, and determined if invader-native functional differences could influence the combined impacts of LUI and invasion. Overall, we found that urban intensification reduced taxonomic richness more strongly at invaded plots (synergistic interactive effects). In contrast, functional richness loss caused by urban intensification was less pronounced at invaded plots (antagonistic interactive effects). Overall models showed also that urban intensification led to reduced mean leaf area, while agriculture was linked to higher mean plant height. When exploring invader-specific models, we observed that the combined effects of agricultural and urban intensification with invasion were heterogeneous. At invaded plots, invader-native functional differences accounted for part of this variability. Our findings demonstrate the importance of considering the interactive effects of global change pressures for a better assessment and management of ecosystems.

Provision of Organ at Risk Contouring Guidance in UK Radiotherapy Clinical Trials.

AIMS: Accurate delineation of organs at risk (OAR) is vital to the radiotherapy planning process. Inaccuracies in OAR delineation arising from imprecise anatomical definitions may affect plan optimisation and risk inappropriate dose delivery to normal tissues. The aim of this study was to review the provision of OAR contouring guidance in National Institute of Health Research Clinical Research Network (NIHR CRN) portfolio clinical trials. MATERIALS AND METHODS: The National Radiotherapy Quality Trials Assurance (RTTQA) Group carried out a two-round Delphi assessment to determine which OAR descriptions provided optimal guidance. RESULTS: Eighty-four clinical trials involving radiotherapy quality assurance were identified as either in recruitment or in setup within the NIHR CRN portfolio. Fifty-nine trials mandated OAR contouring. In total there were 412 OAR; 171 were uniquely named; 159 OAR had more than one name associated with a single structure, with the greatest nomenclature variation seen for the femoral head ± neck, the parotid gland, and bowel. The two-round Delphi assessment determined 42 OAR descriptions as providing optimal contouring guidance. CONCLUSIONS: This study identified the need for OAR nomenclature and contouring guidance consistency across clinical trials. In response to this study and in conjunction with the Global Quality Assurance of Radiation Therapy Clinical Trials Harmonisation Group, the RTTQA Group is in collaboration with international partners to provide consensus recommendations for OAR delineation in clinical trials.

A multicentre audit of HDR/PDR brachytherapy absolute dosimetry in association with the INTERLACE trial (NCT015662405).

A UK multicentre audit to evaluate HDR and PDR brachytherapy has been performed using alanine absolute dosimetry. This is the first national UK audit performing an absolute dose measurement at a clinically relevant distance (20 mm) from the source. It was performed in both INTERLACE (a phase III multicentre trial in cervical cancer) and non-INTERLACE brachytherapy centres treating gynaecological tumours. Forty-seven UK centres (including the National Physical Laboratory) were visited. A simulated line source was generated within each centre's treatment planning system and dwell times calculated to deliver 10 Gy at 20 mm from the midpoint of the central dwell (representative of Point A of the Manchester system). The line source was delivered in a water-equivalent plastic phantom (Barts Solid Water) encased in blocks of PMMA (polymethyl methacrylate) and charge measured with an ion chamber at 3 positions (120° apart, 20 mm from the source). Absorbed dose was then measured with alanine at the same positions and averaged to reduce source positional uncertainties. Charge was also measured at 50 mm from the source (representative of Point B of the Manchester system). Source types included 46 HDR and PDR 192Ir sources, (7 Flexisource, 24 mHDR-v2, 12 GammaMed HDR Plus, 2 GammaMed PDR Plus, 1 VS2000) and 1 HDR 60Co source, (Co0.A86). Alanine measurements when compared to the centres' calculated dose showed a mean difference (±SD) of +1.1% (±1.4%) at 20 mm. Differences were also observed between source types and dose calculation algorithm. Ion chamber measurements demonstrated significant discrepancies between the three holes mainly due to positional variation of the source within the catheter (0.4%-4.9% maximum difference between two holes). This comprehensive audit of absolute dose to water from a simulated line source showed all centres could deliver the prescribed dose to within 5% maximum difference between measurement and calculation.

CSF analysis for protein biomarker identification in patients with leptomeningeal metastases from CNS lymphoma.

INTRODUCTION: Leptomeningeal metastases (LM) from lymphoma remain a difficult complication for oncologist due to the high incidence in morbidity and mortality. Early diagnostic and initiation of treatment are essential to prevent neurological deterioration. Areas covered: In this review, several proteomic approaches are described in order to help and provide the basis for the identification of biomarkers useful in early diagnosis, also in discovery novel targets for therapeutic agents. In fact, the identification of biomarkers will have a high potential to detect leptomeningeal lymphoma, as well as to predict its progression and treatment response. Expert commentary: In the case of LM by Central nervous system (CNS) lymphoma, these studies generated the first insights into the utility of proteomic analysis for biomarker identification and will be demonstrated that identifying specific proteins in cerebrospinal fluid (CSF) had much greater sensitivity for detecting LM in comparison to standard cytological protocols.

Recommendations for Radiotherapy Technique and Dose in Extra-nodal Lymphoma.

Extra-nodal sites may be involved in around 40% of patients with non-Hodgkin lymphoma. The general principles for target volume delineation in this setting are presented, together with specific examples. In general, the entire organ affected should be encompassed in the clinical target volume with an expansion of at least 10 mm, increased in some instances to account for patterns of potential lymphatic flow. Adjacent lymph nodes may be treated using standard techniques for nodal irradiation. Doses for extra-nodal lymphoma follow the same principles as nodal lymphoma, delivering 30 Gy in 15 fractions for Hodgkin and aggressive non-Hodgkin lymphoma and 24 Gy in 12 fractions for indolent lymphomas, with the exception of certain palliative situations, mycosis fungoides, central nervous system lymphoma and natural killer/T-cell lymphoma.

HIN-1: a New Epigenetic Biomarker Crucial for Therapy Selection in Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common brain tumor in adults. The role of high in normal-1 (HIN-1) as a potential biomarker in combating this disease is being described for the first time in this study. A combination of O6-methylguanine DNA methyltransferase (MGMT) and HIN-1 methylation could be a possible biomarker in therapy choice. Interestingly, survival data shows a similar trend for the methylation of MGMT and for unmethylation of HIN-1 and vice versa. Eighty-eight paraffin-embedded brain tumors were analyzed to screen methylation rates of different genes and evaluate the association between genes methylation and clinicopathologic variables. Our study is the first of its kind to indicate that MGMT and HIN-1 methylation status are inverted (97.7% of methylated ones) and could be new markers in the study of GBM prognosis, especially in the therapy selection.

Una rara causa de dolor abdominal en un niño sano / A rare cause of abdominal pain in a healthy child

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Características clínicas y epidemiológicas de carcinoma basoescamoso en cinco años en un hospital de alta complejidad / Clinical and epidemiological features of basosquamous carcinoma in five years in a high complexity hospital

Introducción: el carcinoma basoescamoso es un tipo histológico poco frecuente y de mal pronóstico, presenta características clínicas e histológicas intermedias entre carcinoma espinocelular y basocelular; su diagnóstico es mediante la biopsia y el tratamiento es principalmente quirúrgico. Objetivo: determinar características epidemiológicas y clínicas de casos de carcinomas basoescamosos, diagnosticados en el Hospital Dr. Hernán Henríquez Aravena de Temuco, durante el período 2003-2007 y comparar nuestra realidad con la literatura. Materiales y Métodos: estudio descriptivo retrospectivo, donde se incluyeron todos los individuos con diagnóstico histológico de carcinoma basoescamoso, registrados entre 2003 y 2007 en el Hospital Dr. Hernán Henríquez Aravena de Temuco. Se estudiaron las variables epidemiológicas de sexo y edad al momento del diagnóstico; apellidos mapuches y las variables clínicas de ubicación, forma de presentación (única o múltiple) y correlación clínico-histológica. Resultados: se encontraron 36 casos, 52,8% presentó sexo masculino, el promedio de edades al diagnóstico fue de 74,6 años. 5,6% tenía algún apellido mapuche. Un 80,6% se presentó en cabeza y cuello. En un 63,9% de los casos, el diagnóstico clínico en base a la morfología de la lesión, fue de carcinoma basocelular, no existiendo correlación clínico-histológica en ningún caso. Discusión: los resultados obtenidos por nosotros, mantienen la tendencia respecto de lo que se registra en la literatura en cuanto a: distribución por sexo, edad y ubicación. No encontramos trabajos donde se hable de las características de esta enfermedad en población mapuche. La macroscopía lleva a confusión diagnóstica, por lo que en todos los casos el diagnóstico es histológico.

Introduction: basosquamous cell carcinoma is a rare and poor prognosis histological type, that presents intermediate clinical and histological features between squamous and basal cell carcinoma. The diagnosis is made by biopsy, and the treatment is primarily surgical. Objective: determine epidemiological and clinical characteristics of cases of diagnosed basosquamous cell carcinomas, at Dr. Hernán Henríquez Aravena Hospital of Temuco, during the period 2003-2007 and proceed to compare the results with the literature. Materials and Methods: a retrospective review including all individuals with histological confirmation of basosquamous carcinoma, between 2003 and 2007 at Dr. Hernán Henríquez Aravena Hospital of Temuco. Were considered epidemiological variables of sex, age at diagnosis and mapuche surname, and clinical variables of location of the lesion, presentación (single or multiple) and the clinical-pathologic correlation. Results: 36 cases were found, 52.8% male, the average age at diagnosis was 74.6 years. 5.6% had a mapuche surname. 80.6% occurred in the head and neck. In the 63.9% of the cases, the clinical diagnosis based on the morphology of the lesion was basal cell carcinoma. We did not found clinical-pathologic correlation in any case. Discussion: our results maintain the trend recorded in the literature in relation to sex distribution, age of presentation and location. We did not found works about characteristics of this disease in mapuche population. The macroscopic diagnosis leads to confusion, so the diagnosis it has to be histological in every case.

Características clínicas y epidemiológicas de carcinoma basoescamoso en cinco años en un hospital de alta complejidad / Clinical and epidemiological features of basosquamous carcinoma in five years in a high complexity hospital

Introducción: el carcinoma basoescamoso es un tipo histológico poco frecuente y de mal pronóstico, presenta características clínicas e histológicas intermedias entre carcinoma espinocelular y basocelular; su diagnóstico es mediante la biopsia y el tratamiento es principalmente quirúrgico. Objetivo: determinar características epidemiológicas y clínicas de casos de carcinomas basoescamosos, diagnosticados en el Hospital Dr. Hernán Henríquez Aravena de Temuco, durante el período 2003-2007 y comparar nuestra realidad con la literatura. Materiales y Métodos: estudio descriptivo retrospectivo, donde se incluyeron todos los individuos con diagnóstico histológico de carcinoma basoescamoso, registrados entre 2003 y 2007 en el Hospital Dr. Hernán Henríquez Aravena de Temuco. Se estudiaron las variables epidemiológicas de sexo y edad al momento del diagnóstico; apellidos mapuches y las variables clínicas de ubicación, forma de presentación (única o múltiple) y correlación clínico-histológica. Resultados: se encontraron 36 casos, 52,8% presentó sexo masculino, el promedio de edades al diagnóstico fue de 74,6 años. 5,6% tenía algún apellido mapuche. Un 80,6% se presentó en cabeza y cuello. En un 63,9% de los casos, el diagnóstico clínico en base a la morfología de la lesión, fue de carcinoma basocelular, no existiendo correlación clínico-histológica en ningún caso. Discusión: los resultados obtenidos por nosotros, mantienen la tendencia respecto de lo que se registra en la literatura en cuanto a: distribución por sexo, edad y ubicación. No encontramos trabajos donde se hable de las características de esta enfermedad en población mapuche. La macroscopía lleva a confusión diagnóstica, por lo que en todos los casos el diagnóstico es histológico.(AU)

Introduction: basosquamous cell carcinoma is a rare and poor prognosis histological type, that presents intermediate clinical and histological features between squamous and basal cell carcinoma. The diagnosis is made by biopsy, and the treatment is primarily surgical. Objective: determine epidemiological and clinical characteristics of cases of diagnosed basosquamous cell carcinomas, at Dr. Hernán Henríquez Aravena Hospital of Temuco, during the period 2003-2007 and proceed to compare the results with the literature. Materials and Methods: a retrospective review including all individuals with histological confirmation of basosquamous carcinoma, between 2003 and 2007 at Dr. Hernán Henríquez Aravena Hospital of Temuco. Were considered epidemiological variables of sex, age at diagnosis and mapuche surname, and clinical variables of location of the lesion, presentación (single or multiple) and the clinical-pathologic correlation. Results: 36 cases were found, 52.8% male, the average age at diagnosis was 74.6 years. 5.6% had a mapuche surname. 80.6% occurred in the head and neck. In the 63.9% of the cases, the clinical diagnosis based on the morphology of the lesion was basal cell carcinoma. We did not found clinical-pathologic correlation in any case. Discussion: our results maintain the trend recorded in the literature in relation to sex distribution, age of presentation and location. We did not found works about characteristics of this disease in mapuche population. The macroscopic diagnosis leads to confusion, so the diagnosis it has to be histological in every case.(AU)