Clinical and economic burden of acute exacerbations of idiopathic pulmonary fibrosis: a prospective observational study in Spain (OASIS study).

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal progressive lung disease entailing significant impairment in health-related quality of life (HRQoL) and high socioeconomic burden. The course of IPF includes episodes of acute exacerbations (AE-IPF) leading to poor outcomes. This study aimed to compare management, costs and HRQoL of patients with AE-IPF to patients without AE-IPF during one year in Spain. MATERIALS AND METHODS: In a 12-month, prospective, observational, multicenter study of IPF patients, healthcare resource use was recorded and costs related to AE-IPF were estimated and compared between patients with and without AE-IPF. HRQoL was measured with the St. George's Respiratory Questionnaire (SGRQ), EuroQoL 5 dimensions 5 levels questionnaire (EQ-5D-5L), EQ-5D visual analogue scale (EQ-VAS) and the Barthel Index. RESULTS: 204 IPF patients were included: 22 (10.8%) experienced ≥ 1 acute exacerbation, and 182 (89.2%) did not. Patients with exacerbations required more primary care visits, nursing home visits, emergency visits, hospital admissions, pharmacological treatments and transport use (p < 0.05 for all comparisons). Likewise, patients with exacerbations showed higher annual direct health AE-IPF-related costs. In particular, specialized visits, emergency visits, days of hospitalization, tests, palliative care, transport in ambulance and economic aid (p < 0.05 for all comparisons). Exploratory results showed that patients with AE-IPF reported a non-significant but substantial decline of HRQoL compared with patients without AE-IPF, although causality can be inferred. CONCLUSION: We observed significantly higher resource use and cost consumption and lower HRQoL among patients suffering exacerbations during the study. Thus, preventing or avoiding AE-IPF is key in IPF management.

Memory and language risk assessment with Wada test in patients candidates for epilepsy surgery. / Evaluación de la memoria y el lenguaje mediante el test de Wada en pacientes candidatos a cirugía de epilepsia.

AIM: To determine post-surgical cognitive risk and associated factors according to lesion location in a sample of patients evaluated for epilepsy surgery with Wada test at the Fundacion Instituto Neurologico de Colombia. MATERIALS AND METHODS: An observational, retrospective, analytical study was completed in patients with drug-resistant temporal lobe epilepsy candidates for epilepsy surgery treated from 2001 to 2021, who completed the Wada test as part of the pre-surgical evaluation. A descriptive analysis of sociodemographic, clinical, imaging and neuropsychological variables was completed; a multivariate logistic regression was performed analyzing factors associated with resection risk in patients with left lesions. RESULTS A total of 369 patients were included, 54.74% of the cases were women, with a median age of seizure onset of 11 years. 92.66% of the cases had lesional epilepsy and 68.56% were secondary to hippocampal sclerosis. Left hemisphere was the most frequently affected (65.68%) being dominant for memory and language in most of the patients with a proportion of 42.82% and 81.3%, respectively. The median functional adequacy was 43.75 (IQR 0-75) and the functional reserve was 75 (IQR 25 -93.75). In 104 patients, the Wada test determined a resection risk. In patients with a left lesion, it was found that functional reserve (PRadjusted 0.99, CI 95% 0.9997-0.9998) and having a right hemispheric dominance for memory (PRadjusted 0.92, CI 95% 0.547-0.999) were protective factors for post-surgical resection risk. CONCLUSION: Wada test is a useful tool for surgical decision-making in patients with drug-resistant temporal lobe epilepsy. When considering cognitive risk, components such as memory dominance and functional reserve should be considered as protective factors for postsurgical cognitive function preservation in patients with left lesions.

TITLE: Evaluación de la memoria y el lenguaje mediante el test de Wada en pacientes candidatos a cirugía de epilepsia.Objetivo. Determinar el riesgo cognitivo posquirúrgico y factores asociados según la localización de la lesión en una muestra de pacientes evaluados para cirugía de epilepsia con el test de Wada en la Fundación Instituto Neurológico de Colombia. Materiales y métodos. Se realizó un estudio observacional, retrospectivo y analítico en pacientes con epilepsia farmacorresistente del lóbulo temporal candidatos a cirugía de epilepsia tratados entre 2001 y 2021, que completaron el test de Wada como parte de la evaluación prequirúrgica. Se realizó un análisis descriptivo de variables sociodemográficas, clínicas, imagenológicas y neuropsicológicas. Se realizó una regresión logística multivariada analizando factores asociados al riesgo de resección en pacientes con lesiones izquierdas. Resultados. Se incluyó a 369 pacientes, el 54,74% de los casos fueron mujeres, con una mediana de edad de inicio de las convulsiones de 11 años. El 92,66% de los casos presentó epilepsia lesional; de éstos, el 68,56% fue secundario a esclerosis hipocampal. El hemisferio izquierdo fue el más frecuentemente afectado (65,68%), y éste fue dominante para la memoria y el lenguaje en la mayoría de los pacientes, con una proporción del 42,82 y el 81,3%, respectivamente. La mediana de adecuación funcional fue de 43,75 (rango intercuartílico: 0-75) y la reserva funcional de 75 (rango intercuartílico: 25-93,75). En 104 pacientes, el test de Wada determinó un riesgo de resección. En pacientes con lesiones izquierdas se encontró que la reserva funcional (razón de prevalencia ajustada: 0,99; intervalo de confianza al 95%: 0,9997-0,9998) y tener dominancia del hemisferio derecho para la memoria (razón de prevalencia ajustada: 0,92; intervalo de confianza al 95%: 0,547-0,999) fueron factores asociados para determinar el riesgo de resección posquirúrgico en el test de Wada. Conclusión. El test de Wada es una herramienta útil para la toma de decisiones quirúrgicas en pacientes con epilepsia del lóbulo temporal farmacorresistente. Componentes como la dominancia de la memoria y la reserva funcional en el test de Wada deben considerarse como factores que se deben tener en cuenta en la predicción de la preservación de la función cognitiva posquirúrgica en pacientes con lesiones izquierdas.

Immune-mediated hepatitis: Basic concepts and treatment.

Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized advanced cancer management. Nevertheless, the generalized use of these medications has led to an increase in the incidence of adverse immune-mediated events and the liver is one of the most frequently affected organs. Liver involvement associated with the administration of immunotherapy is known as immune-mediated hepatitis (IMH), whose incidence and clinical characteristics have been described by different authors. It often presents as mild elevations of amino transferase levels, seen in routine blood tests, that spontaneously return to normal, but it can also manifest as severe transaminitis, possibly leading to the permanent discontinuation of treatment. The aim of the following review was to describe the most up-to-date concepts regarding the epidemiology, diagnosis, risk factors, and progression of IMH, as well as its incidence in different types of common cancers, including hepatocellular carcinoma. Treatment recommendations according to the most current guidelines are also provided.

Population based study of morbidity and mortality rates associated to radical prostatectomy cases in Spain.

INTRODUCTION: There is no population-based study that accounts for the number of radical prostatectomies (RP) carried out in Spain, nor regarding the morbidity and mortality of this intervention. Our objective is to study the morbidity and mortality of RP in Spain from 2011 to 2015 and to evaluate the geographic variation. MATERIAL AND METHODS: We designed a retrospective observational study of all patients submitted to RP in Spain during five consecutive years (2011-2015). The data was extracted from the «Conjunto Mínimo Básico de Datos¼ (CMBD). We have evaluated geographic variations in terms of morbidity and hospital stay, and the impact of the mean annual surgical volume for each center on these variables. RESULTS: Between 2011-2015, a total of 37,725 RPs were performed in 221 Spanish public hospitals. The mean age of the series was 63.9±3.23 years. Of all RPs, 50% were performed through an open approach, and 43.4% have been operated on in hospitals with <500 beds. We observed an important variability in the distribution of the cases operated on in the different regions. The regions that perform more RPs are Andalusia, Catalonia, Galicia, and Madrid. Our study shows a complication rate of 8.6%, with hemorrhage and the need for transfusion being the most frequent (5.3 and 4%, respectively). There are significant differences in bleeding rates and hospital stay among regions, which are maintained after adjusting for patient characteristics and type of hospital. When studying the annual surgical volume of each hospital, we find that the impact on the rate of hemorrhage or transfusion is linear; however, hospital stay remains stable at around 5 days from 60 RPs/year. CONCLUSIONS: In national terms, morbidity and mortality rates after RP are comparable to those described in the literature. This study reveals a clear dispersion in the hospitals that carry out this intervention, showing clear differences in terms of morbidity and hospital stay between the different regions.

Mechanistic interrogation of mutation-independent disease modulators of RDEB identifies the small leucine-rich proteoglycan PRELP as a TGF-ß antagonist and inhibitor of fibrosis.

Recessive dystrophic epidermolysis bullosa (RDEB) is a genetic extracellular matrix disease caused by deficiency in type VII collagen (Col VII). The disease manifests with devastating mucocutaneous fragility leading to progressive fibrosis and metastatic squamous cell carcinomas. Although Col VII abundance is considered the main predictor of symptom course, previous studies have revealed the existence of mutation-independent mechanisms that control disease progression. Here, to investigate and validate new molecular modifiers of wound healing and fibrosis in a natural human setting, and toward development of disease-modulating treatment of RDEB, we performed gene expression profiling of primary fibroblast from RDEB siblings with marked phenotypic variations, despite having equal COL7A1 genotype. Gene enrichment analysis suggested that severe RDEB was associated with enhanced response to TGF-ß stimulus, oxidoreductase activity, and cell contraction. Consistently, we found an increased response to TGF-ß, higher levels of basal and induced reactive oxygen species (ROS), and greater contractile ability in collagen lattices in RDEB fibroblasts (RDEBFs) from donors with severe RDEB vs mild RDEB. Treatment with antioxidants allowed a reduction of the pro-fibrotic and contractile phenotype. Importantly, our analyses revealed higher expression and deposition in skin of the relatively uncharacterized small leucine-rich extracellular proteoglycan PRELP/prolargin associated with milder RDEB manifestations. Mechanistic investigations showed that PRELP effectively attenuated fibroblasts' response to TGF-ß1 stimulus and cell contractile capacity. Moreover, PRELP overexpression in RDEBFs enhanced RDEB keratinocyte attachment to fibroblast-derived extracellular matrix in the absence of Col VII. Our results highlight the clinical relevance of pro-oxidant status and hyper-responsiveness to TGF-ß in RDEB severity and progression. Of note, our study also reveals PRELP as a novel and natural TGF-ß antagonist with a likely dermo-epidermal pro-adhesive capacity.

Recommendations of the Society of Thoracic Surgery and the Section of Cardiothoracic and Vascular Surgery of the Spanish Society of Anesthesia, Resuscitation and Pain Therapy, for patients undergoing lung surgery included in an intensified recovery program.

In recent years, multidisciplinary programs have been implemented that include different actions during the pre, intra and postoperative period, aimed at reducing perioperative stress and therefore improving the results of patients undergoing surgical interventions. Initially, these programs were developed for colorectal surgery and from there they have been extended to other surgeries. Thoracic surgery, considered highly complex, like other surgeries with a high postoperative morbidity and mortality rate, may be one of the specialties that most benefit from the implementation of these programs. This review presents the recommendations made by different specialties involved in the perioperative care of patients who require resection of a lung tumor. Meta-analyzes, systematic reviews, randomized and non-randomized controlled studies, and retrospective studies conducted in patients undergoing this type of intervention have been taken into account in preparing the recommendations presented in this guide. The GRADE scale has been used to classify the recommendations, assessing on the one hand the level of evidence published on each specific aspect and, on the other hand, the strength of the recommendation with which the authors propose its application. The recommendations considered most important for this type of surgery are those that refer to pre-habilitation, minimization of surgical aggression, excellence in the management of perioperative pain and postoperative care aimed at providing rapid postoperative rehabilitation.

Usefulness of inflammatory markers in detecting esophagojejunostomy leakage.

INTRODUCTION AND AIM: Total gastrectomy is utilized in different pathologies. Esophagojejunostomy leakage is a frequent complication. Our aim was to determine the association of the neutrophil-lymphocyte ratio (NLR) with esophagojejunostomy leakage that subsequently required invasive treatment. MATERIALS AND METHODS: A retrospective study included patients that underwent esophagojejunostomy within the time frame of 2002-2017. Patients were grouped into those with or without anastomotic leakage that had conservative treatment (group A) and those with anastomotic leakage that had invasive treatment (group B). ROC curves and the Youden index were used for the optimum cutoff values of the NLR. RESULTS: Fifty-seven patients were included. Thirty-two (56.14%) were men, and mean patient age was 61.8 ± 13.4 years. Forty-five patients were assigned to group A and 12 to group B. Mean NLR was higher for group B on postoperative day 3 (group A 9.5 ± 7.5 vs. group B 13.9 ± 4.9) (p = 0.05). Mean total leukocytes was higher in group B on postoperative day 5 (group A 7.8 ± 3.4 × 103/mcl vs. group B 10.3 ± 4.4 × 103/mcl) (p = 0.03). NLR and total leukocyte accuracy on postoperative day 3 was calculated with ROC curves, at 0.78 and 0.63, respectively. For the NLR and leukocyte count, sensitivity was 91.7% and 58%, specificity was 64.4% and 60%, positive predictive value was 40% and 28%, and negative predictive value was 96% and 84%, respectively. CONCLUSIONS: Postoperatively, the NLR identified the total gastrectomy with esophagojejunostomy patients that subsequently required an invasive procedure secondary to esophagojejunostomy leakage.

Recommendations of the Society of Thoracic Surgery and the Section of Cardiothoracic and Vascular Surgery of the Spanish Society of Anesthesia, Resuscitation and Pain Therapy, for patients undergoing lung surgery included in an intensified recovery program. / Recomendaciones de la Sociedad Española de Cirugía Torácica y de la Sección de Cardiotorácica y Cirugía Vascular de la Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor, para los pacientes sometidos a cirugía pulmonar incluidos en un programa de recuperación intensificada.

In recent years, multidisciplinary programs have been implemented that include different actions during the pre, intra and postoperative period, aimed at reducing perioperative stress and therefore improving the results of patients undergoing surgical interventions. Initially, these programs were developed for colorectal surgery and from there they have been extended to other surgeries. Thoracic surgery, considered highly complex, like other surgeries with a high postoperative morbidity and mortality rate, may be one of the specialties that most benefit from the implementation of these programs. This review presents the recommendations made by different specialties involved in the perioperative care of patients who require resection of a lung tumor. Meta-analyses, systematic reviews, randomized and non-randomized controlled studies, and retrospective studies conducted in patients undergoing this type of intervention have been taken into account in preparing the recommendations presented in this guide. The GRADE scale has been used to classify the recommendations, assessing on the one hand the level of evidence published on each specific aspect and, on the other hand, the strength of the recommendation with which the authors propose its application. The recommendations considered most important for this type of surgery are those that refer to pre-habilitation, minimization of surgical aggression, excellence in the management of perioperative pain and postoperative care aimed at providing rapid postoperative rehabilitation.

Short communication: Saliva and salivary components affect goat rumen fermentation in short-term batch incubations.

The research about the role of saliva in ruminants has been mainly focused on its buffering capacity together with facilitation of the rumination process. However, the role of salivary bioactive components on modulating the activity of the rumen microbiota has been neglected until recently. This study developed an in vitro approach to assess the impact of different components in saliva on rumen microbial fermentation. Four different salivary fractions were prepared from four goats: (i) non-filtrated saliva (NFS), (ii) filtrated through 0.25 µm to remove microorganisms and large particles (FS1), (iii) centrifuged through a 30 kDa filter to remove large proteins, (FS2), and (iv) autoclaved saliva (AS) to keep only the minerals. Two experiments were conducted in 24 h batch culture incubations with 6 ml of total volume consisting of 2 ml of rumen fluid and 4 ml of saliva/buffer mix. In Experiment 1, the effect of increasing the proportion of saliva (either NFS or FS1) in the solution (0%, 16%, 33% and 50% of the total volume) was evaluated. Treatment FS1 promoted greater total volatile fatty acids (VFA) (+8.4%) and butyrate molar proportion (+2.8%) but lower NH3-N concentrations than NFS fraction. Replacing the bicarbonate buffer solution by increasing proportions of saliva resulted in higher NH3-N, total VFA (+8.0%) and propionate molar proportion (+11%). Experiment 2 addressed the effect of the different fractions of saliva (NFS, FS1, FS2 and AS). Saliva fractions led to higher total VFA and NH3-N concentrations than non-saliva incubations, which suggests that the presence of some salivary elements enhanced rumen microbial activity. Fraction FS1 promoted a higher concentration of total VFA (+7.8%) than the other three fractions, and higher propionate (+26%) than NFS and AS. This agrees with findings from Experiment 1 and supports that 'microbe-free saliva', in which large salivary proteins are maintained, boosts rumen fermentation. Our results show the usefulness of this in vitro approach and suggest that different salivary components can modulate rumen microbial fermentation, although the specific metabolites and effects they cause need further research.

MRI prostate contouring is not impaired by the use of a radiotherapy image acquisition set-up. An intra- and inter-observer paired comparative analysis with diagnostic set-up images.

PURPOSE: The use of MRI for radiotherapy planning purposes is growing but image acquisition using radiotherapy set-ups has impaired image quality. Whether differences in image acquisition set-up could modify organ contouring has not been evaluated. Therefore, we aimed to evaluate differences in contouring between paired of image sets that were acquired in the same scanning session using different parameters. MATERIAL AND METHODS: Ten patients underwent RT treatment planning with MRI co-registration. MRI was carried out using two different set-ups during the same session, MRI radiotherapy set-ups and MRI diagnostic set-ups. Prostates and rectums were retrospectively contoured in both image sets by 5 radiation oncologists and 4 radiologists. Intra-observer analysis was carried out comparing organ volumes, the Dice coefficient and hausdorff distance values between two contouring rounds. Inter-observer analysis was carried out by comparing individual contours to a generated STAPLE consensus contour, which is considered the gold standard reference. RESULTS: No significant differences were observed between MRI acquisition set-ups. Significant differences were observed for the dice and hausdorff parameters, comparing individual contours to the STAPLE consensus contour, when analysing diagnostic images between rounds, although raw values were similar. CONCLUSION: Prostate and rectum contours did not differ significantly when using diagnostic or radiotherapy MRI acquisition set-ups.

Catéter de drenaje de líquido cefalorraquídeo: usos, técnica y complicaciones para el anestesiólogo / Spinal fluid drainage catheter: uses, technique, and complications for the anesthesiologist

Spinal drainage catheter installation is a procedure indicated essentially in the repair of aortic aneurysms and the neurosurgery setting. It is not always a simple procedure where dilemmas arise about the indication, technique, and complications. The following article reviews each of these topics.

La instalación de un catéter de drenaje espinal es un procedimiento indicado principalmente en la reparación de aneurismas aórticos y en el escenario de neurocirugía. No siempre es un procedimiento fácil de realizar donde surgen dudas sobre indicación, técnica y eventuales complicaciones. En el siguiente artículo revisamos cada uno de estos temas.

Extrahepatic complications of non-alcoholic fatty liver disease: Its impact beyond the liver. / Complicaciones extrahepáticas de la enfermedad por hígado graso no alcohólico: impacto más allá del hígado.

Non-alcoholic fatty liver disease (NAFLD) is currently one of the main causes of chronic liver disease in Western countries, with a 25% prevalence reported in the general population worldwide. Visceral adiposity and liver fat promote a state of systemic inflammation, predisposing individuals with NAFLD to the extrahepatic pathologies of cardiovascular disease (the most common cause of death in patients with NAFLD), diabetes mellitus, chronic kidney disease, hypothyroidism, polycystic ovary syndrome, obstructive sleep apnea, and an increased risk for presenting with gastrointestinal and extraintestinal neoplasias. Different mechanisms between NAFLD and its association with extrahepatic diseases have been reported, and lipotoxicity is the main cause of inflammatory pathway activation that results in extrahepatic tissue damage.

Myths and realities in the management of the open abdomen with negative pressure systems. A case report and literature review.

INTRODUCTION: The open abdomen is a useful resource for treating patients with abdominal hypertension and abdominal compartment syndrome. Currently, early closure assisted with negative pressure devices is considered standard of treatment, and its use has demonstrated favorable outcomes and a decreased rate of complications. PRESENTATION OF A CASE: We present a case of a 32-year-old male patient with diagnosis of non-seminomatous germinal testicular tumor (Stage IIIB (T3-N3-M1), which was summited to surgery, as a complication he presented massive bleeding, that culminated in acute compartment syndrome. With the aforementioned findings the patient re entered the operating room and was managed with open abdomen combined with a medial retraction technique of the abdominal fascia. Currently, the patient has not presented recurrence or late complications after a year. DISCUSSION: The use of negative pressure techniques for open abdomen management began to be generalized in 1995. Subsequently, this technique evolved to V.A.C therapy (Vacuum-assisted closure therapy). Currently, these negative pressure techniques have become the most used method for the temporary closure and management of open abdomen. Controversies continue to limit its widespread use and effectiveness. CONCLUSION: Adequate application of negative pressure therapy in combination with techniques of medial retraction of the abdominal fascia, have proved to be useful in management for patients with open abdomen.

Medicina Regenerativa para Úlceras Crónicas: Aplicación Cutánea de Células Troncales Mesenquimales de Gelatina de Wharton / Regenerative Medicine for Chronic Ulcers: Cutaneous Application of Mesenchymal Stem Cells of Wharton's Jelly

Resumen El empleo de células mesenquimales ha emergido como una parte importante en la medicina regenerativa con efectos positivos en la recuperación de tejidos dañados o perdidos. Las úlceras crónicas incluyen lesiones cutáneas que afectan a una gran parte de la población con diabetes mellitus, (por ejemplo 9.14% desarrollan lesiones por pie diabético según ENSANUT 2016) y representan gastos económicos considerables, debido a la pobre calidad de vida que llevan los pacientes. El tratamiento convencional que se lleva a cabo en estos casos es a largo plazo, y los efectos benéficos generados que se presentan son limitados, ya que las lesiones reinciden por no contar con un tratamiento específico y regenerativo, solo paliativo. Es por ello que en este trabajo se obtuvieron y emplearon células troncales mesenquimales derivadas de gelatina de Wharton (CTM-GW) bajo los criterios propuestos por la Sociedad Internacional de la Terapia Celular. El tratamiento fue aplicado en dos pacientes con úlceras crónicas flebostáticas de diferentes condiciones médicas y se monitoreo a corto plazo, por lo que fue un estudio limitado. Los resultados mostraron que las CTM-GW indujeron la reconstrucción cutánea mediante formación de tejido de granulación, además de disminuir el proceso inflamatorio crónico en la zona de daño, lo que favoreció el índice de cierre de la herida. Por lo anterior, se propone la utilización de CTM-GW en úlceras flebostáticas crónicas como tratamiento en la regeneración de la estructura tisular con resultados a corto plazo.

Abstract Use of mesenchymal cells has emerged as an important part in regenerative medicine with positive effects in the recovery of damaged or lost tissues. Chronic ulcers include skin lesions that affect a large part of the population with diabetes mellitus, (for example, 9.14 develop diabetic foot according to ENSANUT 2016) and represent considerable economic expenses, due to poor quality of life in patients. The conventional treatment that is carried out in these cases is long term, and the generated beneficial effects that are presented are limited, since the injuries recur due to not having a specific and regenerative treatment, only palliative. That is why in this work they were obtained and used mesenchymal stem cells derived from Wharton's jelly (MSC-WJ) under the criteria proposed by the International Society for Cell Therapy. The treatment was applied in two patients with chronic ulcers phlebostatic of different medical conditions and short-term monitoring, so it was a limited study. The results showed that MSC-WJ induced skin reconstruction by tissue formation granulation, in addition to decreasing the chronic inflammatory process in the area of damage, which favored the index of wound healing. Therefore, the use of MSC-WJ in chronic phlebostatic ulcers is proposed as a treatment in the regeneration of the tissue structure with short-term results.

Liver damage in bleomycin-induced pulmonary fibrosis in mice.

Pulmonary fibrosis is an emerging disease with a poor prognosis and high mortality rate that is even surpassing some types of cancer. This disease has been linked to the concomitant appearance of liver cirrhosis. Bleomycin-induced pulmonary fibrosis is a widely used mouse model that mimics the histopathological and biochemical features of human systemic sclerosis, an autoimmune disease that is associated with inflammation and expressed in several corporal systems as fibrosis or other alterations. To determine the effects on proliferation, redox and inflammation protein expression markers were analyzed by immunohistochemistry. Analyses showed a significant increase in protein oxidation levels by lipoperoxidation bio-products and in proliferation and inflammation processes. These phenomena were associated with the induction of the redox status in mice subjected to 100 U/kg bleomycin. These findings clearly show that the bleomycin model induces histopathological alterations in the liver and partially reproduces the complexity of systemic sclerosis. Our results using the bleomycin-induced pulmonary fibrosis model provide a protocol to investigate the mechanism underlying the molecular alteration found in the liver linked to systemic sclerosis.

Effectiveness of fentanyl pectin nasal citrate in controlling episodes of breakthrough cancer pain triggered by routine radiotherapy procedures.

PURPOSE: The aim of the study was to evaluate the effectiveness of fentanyl pectin nasal spray (FPNS) in controlling procedural breakthrough cancer pain (BTCP) in advanced cancer patients undergoing radiotherapy. MATERIALS AND METHODS: This study involved 62 advanced cancer patients, with well-controlled background pain, who presented BTCP associated to routine radiotherapy procedures, treated with FPNS according to our protocol of administration. The BPE intensity was measured using a visual analog scale (VAS). RESULTS: The BTCP was triggered during the computed tomography simulation (79.3%) or treatment delivery (20.7%). Patients indicated a mean VAS of 8.8 (range 7-10) when attempting the procedure. After 4.5 min (range 2-10) of the first FPNS dose, the majority of patients (85.5%) indicated a VAS of 4.3 (range 2-6). 15.5% of the patients did not respond after 15 min; requiring a second dose. All these patients responded, reporting a mean VAS of 4.2 (range 4-6) after 3.0 min (range 2-5) of the second dose. None of the patients required a third dose, nor reported an AE after the administration of FPNS. CONCLUSIONS: In our knowledge, our study is the one of highest recruitment, and with the fastest response of BTCP treated with FPNS reported in advanced cancer patients undergoing radiotherapy. FPNS has proven to be highly effective in reducing the intensity of procedural BTCP in a very short period of time.

An MRI comparative image evaluation under diagnostic and radiotherapy planning set-ups using a carbon fibre tabletop for pelvic radiotherapy.

PURPOSE: To quantitatively and qualitatively evaluate and compare MR images acquired from the usual diagnostic set-up with images acquired in a radiotherapy set-up. MATERIALS AND METHODS: MR images of a phantom and 18 prostate cancer patients imaging using the usual diagnostic set-up with a curved tabletop (DX-set-up) and using a radiotherapy set-up (RT-set-up) with a flat tabletop, were analysed retrospectively. Quantitative assessments were made by measuring signal-to-noise ratio (SNR) and contrast to noise ratio (CNR). Non-parametric tests were used. Qualitative assessments were made independently by three radiologists. Inter-rater reliability was measured as the percentage of agreement and Gwet's AC2 test. RESULTS: The use of the RT-set-up was linked to 19.3% SNR drop on the phantom image. Up to 24% SNR prostate drop was observed in patients' images. Up to 34% CNR drop was observed in patients' images. Although image quality of the RT-set-up was acceptable, all measured domains were worse than the corresponding DX-set-up. Additionally diagnostic images were linked to a better percentage of agreement among raters. CONCLUSIONS: SNR, CNR and image quality were significantly worse when using the RT-set-up than with the DX-set-up although Image quality in the RT-set-up was acceptable.

A comprehensive analysis of factors related to carmustine/bevacizumab response in recurrent glioblastoma.

PURPOSE: Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM. METHODS/PATIENTS: In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status. RESULTS: Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0-9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2-28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5-11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%). CONCLUSIONS: BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.

Nodal FDG-PET/CT uptake influences outcome and relapse location among esophageal cancer patients submitted to chemotherapy or radiochemotherapy.

PURPOSE: Our aim was investigate whether lymph node uptake is associated with survival and regional relapses, and relapse patterns with respect to the radiotherapy fields in esophageal cancer (EC). MATERIALS AND METHODS: The FDG-PET/CT image datasets of 56 patients were analyzed. All patients underwent definitive or neoadjuvant radio/chemotherapy (RCT). All patients suffering from persistent or recurrent local/regional-only disease after RCT were considered for salvage resection. Patients with adenocarcinoma without metastatic disease were considered for planned resection (usually within 3 months of treatment). RESULTS: Patients with PET-positive lymph nodes before treatment had a worse overall survival and a shorter disease-free survival than those without PET-positive nodes. They also had worse node and metastatic relapse-free survival. N2 patients had statistically significant poorer outcomes than N1-N0 patients and a better survival if the involved nodes were closer to the esophageal tumor. Involved node location by PET/CT also affected global, nodal and metastatic relapses. In addition, an increment of SUVmax value increased relative risk of death and increased relative risk of node and metastatic relapses. The first site of relapse was metastatic recurrence and, second, local recurrence. The most frequent were "in-field" loco/regional recurrence. We observed a relationship between patients classified-N1 and out-field nodal recurrence (p = 0.024), and between patients-N2 and in-field nodal recurrence. The number of PET-positive nodes was an independent significant prognostic predictor for relapse (p < 0.001). CONCLUSION: Our study shows that only FDG-PET/CT can provide prognostic information in EC. Nodal PET/CT uptake influences outcome and relapse location among EC patients.