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.

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.

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.

Recommendations for the use of radiotherapy in nodal lymphoma.

These guidelines have been developed to define the use of radiotherapy for lymphoma in the current era of combined modality treatment taking into account increasing concern over the late side-effects associated with previous radiotherapy. The role of reduced volume and reduced doses is addressed, integrating modern imaging with three-dimensional planning and advanced techniques of treatment delivery. Both wide-field and involved-field techniques have now been supplanted by the use of defined volumes based on node involvement shown on computed tomography (CT) and positron emission tomography (PET) imaging and applying the International Commission on Radiation Units and Measurements concepts of gross tumour volume (GTV), clinical target volume (CTV) and planning target volume (PTV). The planning of lymphoma patients for radical radiotherapy should now be based upon contrast enhanced 3 mm contiguous CT with three-dimensional definition of volumes using the convention of GTV, CTV and PTV. The involved-site radiotherapy concept defines the CTV based on the PET-defined pre-chemotherapy sites of involvement with an expansion in the cranio-caudal direction of lymphatic spread by 1.5 cm, constrained to tissue planes such as bone, muscle and air cavities. The margin allows for uncertainties in PET resolution, image registration and changes in patient positioning and shape. There is increasing evidence in both Hodgkin and non-Hodgkin lymphoma that traditional doses are higher than necessary for disease control and related to the incidence of late effects. No more than 30 Gy for Hodgkin and aggressive non-Hodgkin lymphoma and 24 Gy for indolent lymphomas is recommended; lower doses of 20 Gy in combination therapy for early-stage low-risk Hodgkin lymphoma may be sufficient. As yet there are no large datasets validating the use of involved-site radiotherapy; these will emerge from the current generation of clinical trials. Radiotherapy remains the most effective single modality in the treatment of lymphoma. A reduction in both treatment volume and overall treatment dose should now be considered to minimise the risks of late sequelae. However, it is important that this is not at the expense of the excellent disease control currently achieved.

Three novel mutations in the CFTR gene identified in Galician patients.

We report three novel CFTR missense mutations detected in Spanish patients from Galicia (North West of Spain). In the first case, a patient homozygous for a novel S1045Y mutation died due to pulmonary problems. In the other two cases, both heterozygous for novel mutations combined with the F508del mutation, clinical symptoms were different depending on the mutation, detected as M595I and A107V.

Treatment planning and delivery of involved field radiotherapy in advanced Hodgkin's disease: results from a questionnaire-based audit for the UK Stanford V regimen vs ABVD clinical trial quality assurance programme (ISRCTN 64141244).

This questionnaire forms the basis of the quality assurance (QA) programme for the UK randomized Phase III study of the Stanford V regimen versus ABVD for treatment of advanced Hodgkin's disease to assess differences between participating centres in treatment planning and delivery of involved-field radiotherapy for Hodgkin's lymphoma The questionnaire, which was circulated amongst 42 participating centres, consisted of seven sections: target volume definition and dose prescription; critical structures; patient positioning and irradiation techniques; planning; dose calculation; verification; and future developments The results are based on 25 responses. One-third plan using CT alone, one-third use solely the simulator and the rest individualize, depending on disease site. Eleven centres determine a dose distribution for each patient. Technique depends on disease site and whether CT or simulator planning is employed. Most departments apply isocentric techniques and use immobilization and customized shielding. In vivo dosimetry is performed in 7 centres and treatment verification occurs in 24 hospitals. In conclusion, the planning and delivery of treatment for lymphoma patients varies across the country. Conventional planning is still widespread but most centres are moving to CT-based planning and virtual simulation with extended use of immobilization, customized shielding and compensation.

Hemorragia subaracnoidea espontánea / Subarachnoid haemorrahage

La hemorragia subaracnoidea espontánea, es la ruptura de una arteria al espacio subaracnoidea, la causa más frecuente es la ruptura de un aneurisma cerebral, la mortalidad en el momento de la rupturaes cercana a 50, los aneurisma cerebrales son más frecuentes en mujeres en la quinta y sexta década de la vida; los aneurismas del sistema carotideo o circulación anterior representan el 90 y los del sistema vertebro basilar el 8-10. Los aneurismas de la arteria comunicante anterior, arteri comunicante posterior y arteria cerebral media son los más frecuentes. En el territorio posterior lo aneurismas más frecuentes son los de la bifurcación de la arteria basilar. El síntoma cardinal de la ruptura de un aneurisma cerebrocerebral, punción lumbar y panangiografía cerebral. El tratamiento de elección es la oclusión del aneurisma mediante técnicas microquirúrgicas. Otra opción de tratamiento es el tratamiento endovascular del aneurisma. Las principales complicaciones de la ruptura de un aneurisma cerebral son: el resangrado, el vasoespasmo, las convulsiones y la hidrocefaliaal es la cefalea súbita de gran intensidad. El diagnóstico es clínico y se confirma con la escanografía.

Microscale purification of proteins exhibiting anomalous electrophoretic migration: application to the analysis of GAP-43 phosphorylation.

Quite often, in vivo analysis of posttranslational protein modifications is complicated by the lack of specific antibodies or unsatisfactory immunoprecipitation efficiency. Here, we present an alternative method to immunoprecipitation that takes advantage of the anomalous electrophoretic behavior exhibited by GAP-43. This method can be applied to other proteins which show similar characteristics, such as myristoylated alanine-rich C kinase, NAP-22, and Neurogranin, among others. All these proteins display relative mobility values that depend on the concentration of polyacrylamide used in the resolving gel. Cell extracts or tissue homogenates are first separated by SDS-PAGE in 15% polyacrylamide gels, and the bands containing GAP-43 are identified, excised from the gel, and rerun on a second SDS-PAGE in 7.5% polyacrylamide/6 M urea gels. To quickly identify the position of GAP-43 in the first gel, a small amount of fluorescein-labeled recombinant GAP-43 was added to the initial extracts. The method, applied to the analysis of GAP-43 phosphorylation in rat hippocampal slices, can be typically completed in less than 4 h. The excellent yields of purification obtained contributed to a greater accuracy and increased reliability of the radioactivity measurements. It also allowed further processing of the samples, including the analysis of the different phosphorylation sites by proteolytic digestion and peptide mapping.

[Evaluation of transparietal hepatic cholangiography in the diagnosis of cholestatic syndrome]. / Valoración de la colangiografía transparietohepática en el diagnóstico del síndrome colestásico.

Three hundred and thirty-two percutaneous cholangiograms were done in 313 patients. The etiology was benign in 137 cases and malignant in 152 instances. The level of obstruction was correctly localized in 97.8% of cases. The total sensitivity was 88.5% and specificity 95.9%. Positive predictive value 95.4% and negative predictive value 89.6%. Major complications occurred in 3.3% of cases. Complications occurred more frequently when the bile ducts were dilated. They were not related to the number of attempts to puncture ther biliary tree or the experience of the physician.

[Antibiotic prevention in gastroduodenal surgery]. / Profilaxis antibiótica en cirugía gastroduodenal.

The authors present a prospective randomized double-blind clinical trial, including 179 patients submitted to elective gastrointestinal surgery, for the purpose of evaluating three philosophic conceps of antibiotic prophylaxis (PA): systematic antibiotic prophylaxis for 48 h with sodium cefuroxim, 1.5 g the first dose and subsequent doses of 750 mg iv; selective antibiotic prophylaxis based on determination of preoperative gastric pH (pH less than 4, no antibiotic prophylaxis, and pH greater than 4, prophylaxis as in group I); and antibiotic therapy beginning postoperatively with cefuroxim 750 mg every 78 h for 4 days. The postoperative infection rate was 2% in the systematic prophylaxis group, 4% in the selective prophylaxis group, 24% in the antibiotic therapy group and 17.2% in the control group (p less than 0.001). The postoperative infection rate between the systematic and elective prophylaxis groups was statistically similar (p = NS). In conclusion, selective antibiotic prophylaxis has an incidence of postoperative infection similar to that of systematic prophylaxis, and, oriented by gastric pH determination, can be indicated only in patients with bacterogastria. Finally, we confirm that antibiotic therapy of postoperative onset should be eliminated as a method of prevention of postoperative infection.