Rationale and design of RESILIENCE: A prospective randomized clinical trial evaluating remote ischaemic conditioning for the prevention of anthracycline cardiotoxicity.

AIMS: There is a lack of therapies able to prevent anthracycline cardiotoxicity (AC). Remote ischaemic conditioning (RIC) has shown beneficial effects in preclinical models of AC. METHODS: REmote iSchemic condItioning in Lymphoma PatIents REceiving ANthraCyclinEs (RESILIENCE) is a multinational, prospective, phase II, double-blind, sham-controlled, randomized clinical trial that evaluates the efficacy and safety of RIC in lymphoma patients receiving anthracyclines. Patients scheduled to undergo ≥5 chemotherapy cycles including anthracyclines and with ≥1 AC-associated risk factors will be randomized to weekly RIC or sham throughout the chemotherapy period. Patients will undergo three multiparametric cardiac magnetic resonance (CMR) studies, at baseline, after the third cycle (intermediate CMR), and 2 months after the end of chemotherapy. Thereafter, patients will be followed up for clinical events over an anticipated median of ≥24 months. The primary endpoint is the absolute change from baseline in CMR-based left ventricular ejection fraction (LVEF). The main secondary outcome is the incidence of AC events, defined as (1) a drop in CMR-based LVEF of ≥10 absolute points, or (2) a drop in CMR-based LVEF of ≥5 and <10 absolute points to a value <50%. Intermediate CMR will test the ability of T2 mapping to predict AC versus classical markers (left ventricular strain and cardiac injury biomarkers). A novel CMR sequence allowing ultrafast cine acquisition will be validated in this vulnerable population. CONCLUSIONS: The RESILIENCE trial will test RIC (a novel non-invasive intervention to prevent AC) in a cohort of high-risk patients. The trial will also test candidate markers for their capacity to predict AC and will validate a novel CMR sequence reducing acquisition time in a vulnerable population.

Magnetic resonance imaging reference values for cardiac morphology, function and tissue composition in adolescents.

Background: Cardiovascular magnetic resonance (CMR) is a precise tool for the assessment of cardiac anatomy, function, and tissue composition. However, studies providing CMR reference values in adolescence are scarce. We aim to provide sex-specific CMR reference values for biventricular and atrial dimensions and function and myocardial relaxation times in this population. Methods: Adolescents aged 15-18 years with no known cardiovascular disease underwent a non-contrast 3-T CMR scan between March 2021 and October 2021. The imaging protocol included a cine steady-state free-precession sequence for the analysis of chamber size and function, as well as T2-GraSE and native MOLLI T1-mapping for the characterization of myocardial tissue. Findings: CMR scans were performed in 123 adolescents (mean age 16 ± 0.5 years, 52% girls). Mean left and right ventricular end-diastolic indexed volumes were higher in boys than in girls (91.7 ± 11.6 vs 78.1 ± 8.3 ml/m2, p < 0.001; and 101.3 ± 14.1 vs 84.1 ± 10.5 ml/m2, p < 0.001), as was the indexed left ventricular mass (48.5 ± 9.6 vs 36.6 ± 6.0 g/m2, p < 0.001). Left ventricular ejection fraction showed no significant difference by sex (62.2 ± 4.1 vs 62.8 ± 4.2%, p = 0.412), whereas right ventricular ejection fraction trended slightly lower in boys (55.4 ± 4.7 vs. 56.8 ± 4.4%, p = 0.085). Indexed atrial size and function parameters did not differ significantly between sexes. Global myocardial native T1 relaxation time was lower in boys than in girls (1215 ± 23 vs 1252 ± 28 ms, p < 0.001), whereas global myocardial T2 relaxation time did not differ by sex (44.4 ± 2.0 vs 44.1 ± 2.4 ms, p = 0.384). Sex-stratified comprehensive percentile tables are provided for most relevant cardiac parameters. Interpretation: This cross-sectional study provides overall and sex-stratified CMR reference values for cardiac dimensions and function, and myocardial tissue properties, in adolescents. This information is useful for clinical practice and may help in the differential diagnosis of cardiac diseases, such as cardiomyopathies and myocarditis, in this population. Funding: Instituto de Salud Carlos III (PI19/01704).

Multicenter clinical trial for the resection of rectal polyps using a new laparoendoscopic hybrid transanal access device.

INTRODUCTION: Complex polyps require the use of advanced endoscopic techniques or minimally invasive surgery for their approach. In rectal polyps it is of special relevance to reach a consensus on the best approach to avoid under- or overtreatment that increases unnecessary morbidity and mortality. METHODS: We describe a prospective, multicenter, pilot clinical trial with a first-in-human medical device. It is hypothesized that UNI-VEC® facilitates transanal laparoendoscopic surgery for the removal of early rectal tumors. The primary objective is to evaluate that it is safe and meets the established functional requirements. Secondary objectives are to evaluate results, complications and level of satisfaction. RESULTS: 16 patients were recruited in 12 months with a minimum follow-up of 2 months. The mean size was 3.4 cm with the largest polyp being 6 cm. Regarding location, the mean was 6.6 cm from the anal margin. Endoscopic Mucosal Resection (EMR) (6.3%), Endoscopic Submucosal Dissection ESD (43.8%), REC (6.3%) and TAMIS (43.8%) were performed. The mean time was 73.25 min. The 56.3% used a 30° camera and 43.8% used the flexible endoscope as a viewing instrument. The 56.3% were benign lesions and 43.8% malignant. Complete resection is achieved in 87.5%. Regarding complications, mild bleeding (Clavien I) occurred in 25%, 6.3% and 21.4% at 24 h, 48 h and 7 days respectively. Continence was assessed according to the Wexner scale. At 7 days, 60% showed perfect continence, 26.7% mild FI and 13.3% moderate FI. At 30 days, 66.7% had perfect continence, 20% mild FI and 13.3% moderate FI. At 2 months, 4 patients were reviewed who at 30 days had a Wexner's degree higher than preoperative and perfect continence was demonstrated in 25% of the patients, 50% mild and 25% moderate. In no case did rectal perforation or major complications requiring urgent reintervention occur. As for the level of reproducibility, safety, level of satisfaction with the device and evaluation of the blister, the evaluation on a scale of 0-10 (9.43, 9.71, 9.29 and 9.50 respectively). All the investigators have previous experience with transanal devices. CONCLUSIONS: The study demonstrates the efficacy and safety of UNI-VEC® for the treatment of rectal lesions. It will facilitate the implementation of hybrid procedures that seek to solve the limitations of pure endoscopic techniques by allowing the concomitant use of conventional laparoscopic and robotic instrumentation with the flexible endoscope.

Bone marrow activation in response to metabolic syndrome and early atherosclerosis.

AIMS: Experimental studies suggest that increased bone marrow (BM) activity is involved in the association between cardiovascular risk factors and inflammation in atherosclerosis. However, human data to support this association are sparse. The purpose was to study the association between cardiovascular risk factors, BM activation, and subclinical atherosclerosis. METHODS AND RESULTS: Whole body vascular 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) was performed in 745 apparently healthy individuals [median age 50.5 (46.8-53.6) years, 83.8% men] from the Progression of Early Subclinical Atherosclerosis (PESA) study. Bone marrow activation (defined as BM 18F-FDG uptake above the median maximal standardized uptake value) was assessed in the lumbar vertebrae (L3-L4). Systemic inflammation was indexed from circulating biomarkers. Early atherosclerosis was evaluated by arterial metabolic activity by 18F-FDG uptake in five vascular territories. Late atherosclerosis was evaluated by fully formed plaques on MRI. Subjects with BM activation were more frequently men (87.6 vs. 80.0%, P = 0.005) and more frequently had metabolic syndrome (MetS) (22.2 vs. 6.7%, P < 0.001). Bone marrow activation was significantly associated with all MetS components. Bone marrow activation was also associated with increased haematopoiesis-characterized by significantly elevated leucocyte (mainly neutrophil and monocytes) and erythrocyte counts-and with markers of systemic inflammation including high-sensitivity C-reactive protein, ferritin, fibrinogen, P-selectin, and vascular cell adhesion molecule-1. The associations between BM activation and MetS (and its components) and increased erythropoiesis were maintained in the subgroup of participants with no systemic inflammation. Bone marrow activation was significantly associated with high arterial metabolic activity (18F-FDG uptake). The co-occurrence of BM activation and arterial 18F-FDG uptake was associated with more advanced atherosclerosis (i.e. plaque presence and burden). CONCLUSION: In apparently healthy individuals, BM 18F-FDG uptake is associated with MetS and its components, even in the absence of systemic inflammation, and with elevated counts of circulating leucocytes. Bone marrow activation is associated with early atherosclerosis, characterized by high arterial metabolic activity. Bone marrow activation appears to be an early phenomenon in atherosclerosis development.[Progression of Early Subclinical Atherosclerosis (PESA); NCT01410318].

Coronary microcirculation damage in anthracycline cardiotoxicity.

AIMS: The aim of this study was to study changes in coronary microcirculation status during and after several cycles of anthracycline treatment. METHODS AND RESULTS: Large-white male pigs (n=40) were included in different experimental protocols (ExPr.) according to anthracycline cumulative exposure [0.45 mg/kg intracoronary (IC) doxorubicin per injection] and follow-up: control (no doxorubicin); single injection and sacrifice either at 48 h (ExPr. 1) or 2 weeks (ExPr. 2); 3 injections 2 weeks apart (low cumulative dose) and sacrifice either 2 weeks (ExPr. 3) or 12 weeks (ExPr. 4) after third injection; five injections 2 weeks apart (high cumulative dose) and sacrifice 8 weeks after fifth injection (ExPr. 5). All groups were assessed by serial cardiac magnetic resonance (CMR) to quantify perfusion and invasive measurement of coronary flow reserve (CFR). At the end of each protocol, animals were sacrificed for ex vivo analyses. Vascular function was further evaluated by myography in explanted coronary arteries of pigs undergoing ExPr. 3 and controls. A single doxorubicin injection had no impact on microcirculation status, excluding a direct chemical toxicity. A series of five fortnightly doxorubicin injections (high cumulative dose) triggered a progressive decline in microcirculation status, evidenced by reduced CMR-based myocardial perfusion and CFR-measured impaired functional microcirculation. In the high cumulative dose regime (ExPr. 5), microcirculation changes appeared long before any contractile defect became apparent. Low cumulative doxorubicin dose (three bi-weekly injections) was not associated with any contractile defect across long-term follow-up, but provoked persistent microcirculation damage, evident soon after third dose injection. Histological and myograph evaluations confirmed structural damage to arteries of all calibres even in animals undergoing low cumulative dose regimes. Conversely, arteriole damage and capillary bed alteration occurred only after high cumulative dose regime. CONCLUSION: Serial in vivo evaluations of microcirculation status using state-of-the-art CMR and invasive CFR show that anthracyclines treatment is associated with progressive and irreversible damage to the microcirculation. This long-persisting damage is present even in low cumulative dose regimes, which are not associated with cardiac contractile deficits. Microcirculation damage might explain some of the increased incidence of cardiovascular events in cancer survivors who received anthracyclines without showing cardiac contractile defects.

Remote ischaemic preconditioning ameliorates anthracycline-induced cardiotoxicity and preserves mitochondrial integrity.

AIMS: Anthracycline-induced cardiotoxicity (AIC) is a serious adverse effect among cancer patients. A central mechanism of AIC is irreversible mitochondrial damage. Despite major efforts, there are currently no effective therapies able to prevent AIC. METHODS AND RESULTS: Forty Large-White pigs were included. In Study 1, 20 pigs were randomized 1:1 to remote ischaemic preconditioning (RIPC, 3 cycles of 5 min leg ischaemia followed by 5 min reperfusion) or no pretreatment. RIPC was performed immediately before each intracoronary doxorubicin injections (0.45 mg/kg) given at Weeks 0, 2, 4, 6, and 8. A group of 10 pigs with no exposure to doxorubicin served as healthy controls. Pigs underwent serial cardiac magnetic resonance (CMR) exams at baseline and at Weeks 6, 8, 12, and 16, being sacrifice after that. In Study 2, 10 new pigs received 3 doxorubicin injections (with/out preceding RIPC) and were sacrificed at week 6. In Study 1, left ventricular ejection fraction (LVEF) depression was blunted animals receiving RIPC before doxorubicin (RIPC-Doxo), which had a significantly higher LVEF at Week 16 than doxorubicin treated pigs that received no pretreatment (Untreated-Doxo) (41.5 ± 9.1% vs. 32.5 ± 8.7%, P = 0.04). It was mainly due to conserved regional contractile function. In Study 2, transmission electron microscopy (TEM) at Week 6 showed fragmented mitochondria with severe morphological abnormalities in Untreated-Doxo pigs, together with upregulation of fission and autophagy proteins. At the end of the 16-week Study 1 protocol, TEM revealed overt mitochondrial fragmentation with structural fragmentation in Untreated-Doxo pigs, whereas interstitial fibrosis was less severe in RIPC+Doxo pigs. CONCLUSION: In a translatable large-animal model of AIC, RIPC applied immediately before each doxorubicin injection resulted in preserved cardiac contractility with significantly higher long-term LVEF and less cardiac fibrosis. RIPC prevented mitochondrial fragmentation and dysregulated autophagy from AIC early stages. RIPC is a promising intervention for testing in clinical trials in AIC.

Afectación intestinal por un hongo dematiáceo / Intestinal disease by a dematiaceous fungi

Resumen Introducción: Los hongos dematiáceos se caracterizan por la presencia de abundante melanina en su pared celular. Presentan una distribución mundial, siendo más comunes en climas tropicales y subtropicales. Producen infecciones cutáneas y subcutáneas, además de enfermedades alérgicas, neumonías, abscesos cerebrales o infecciones diseminadas. Caso Clínico: Presentamos el caso de un paciente con adenocarcinoma de recto intervenido quirúrgicamente con hallazgo incidental de divertículo de Meckel y en el cual en el estudio anatomopatológico reveló la presencia de un hongo dematiáceo

Introduction: Dematiaceous fungi are characterized by the presence of brown melanine or melanine like pigments in their cell wall. They are generally distributed worldwide, being more common in tropical and subtropical climates. The clinical syndromes are often cutaneous and subcutaneous infections, but can be also responsible of allergic diseases, pneumonias, cerebral abscesses or disseminated infections. Clinical Case: We present the case of a patient with a diagnosis of rectal adenocarcinoma intervening surgically and with an incidental finding of Meckel's Diverticulum. The anatomopathological study revealed the presence of a dematiaceous fungi.

Follow-up of late-onset Pompe disease patients with muscle magnetic resonance imaging reveals increase in fat replacement in skeletal muscles.

BACKGROUND: Late-onset Pompe disease (LOPD) is a genetic disorder characterized by progressive degeneration of the skeletal muscles produced by a deficiency of the enzyme acid alpha-glucosidase. Enzymatic replacement therapy with recombinant human alpha-glucosidase seems to reduce the progression of the disease; although at the moment, it is not completely clear to what extent. Quantitative muscle magnetic resonance imaging (qMRI) is a good biomarker for the follow-up of fat replacement in neuromuscular disorders. The aim of this study was to describe the changes observed in fat replacement in skeletal muscles using qMRI in a cohort of LOPD patients followed prospectively. METHODS: A total of 36 LOPD patients were seen once every year for 4 years. qMRI, several muscle function tests, spirometry, activities of daily living scales, and quality-of-life scales were performed on each visit. Muscle MRI consisted of two-point Dixon studies of the trunk and thigh muscles. Computer analysis of the images provided the percentage of muscle degenerated and replaced by fat in every muscle (known as fat fraction). Longitudinal analysis of the measures was performed using linear mixed models applying the Greenhouse-Geisser test. RESULTS: We detected a statistically significant and continuous increase in mean thigh fat fraction both in treated (+5.8% in 3 years) and in pre-symptomatic patients (+2.6% in 3years) (Greenhouse-Geisser p < 0.05). As an average, fat fraction increased by 1.9% per year in treated patients, compared with 0.8% in pre-symptomatic patients. Fat fraction significantly increased in every muscle of the thighs. We observed a significant correlation between changes observed in fat fraction in qMRI and changes observed in the results of the muscle function tests performed. Moreover, we identified that muscle performance and mean thigh fat fraction at baseline visit were independent parameters influencing fat fraction progression over 4 years (analysis of covariance, p < 0.05). CONCLUSIONS: Our study identifies that skeletal muscle fat fraction continues to increase in patients with LOPD despite the treatment with enzymatic replacement therapy. These results suggest that the process of muscle degeneration is not stopped by the treatment and could impact muscle function over the years. Hereby, we show that fat fraction along with muscle function tests can be considered a good outcome measures for clinical trials in LOPD patients.

Higher-order diffusion MRI characterization of mesorectal lymph nodes in rectal cancer.

PURPOSE: Mesorectal lymph node staging plays an important role in treatment decision making. Here, we explore the benefit of higher-order diffusion MRI models accounting for non-Gaussian diffusion effects to classify mesorectal lymph nodes both 1) ex vivo at ultrahigh field correlated with histology and 2) in vivo in a clinical scanner upon patient staging. METHODS: The preclinical investigation included 54 mesorectal lymph nodes, which were scanned at 16.4 T with an extensive diffusion MRI acquisition. Eight diffusion models were compared in terms of goodness of fit, lymph node classification ability, and histology correlation. In the clinical part of this study, 10 rectal cancer patients were scanned with diffusion MRI at 1.5 T, and 72 lymph nodes were analyzed with Apparent Diffusion Coefficient (ADC), Intravoxel Incoherent Motion (IVIM), Kurtosis, and IVIM-Kurtosis. RESULTS: Compartment models including restricted and anisotropic diffusion improved the preclinical data fit, as well as the lymph node classification, compared to standard ADC. The comparison with histology revealed only moderate correlations, and the highest values were observed between diffusion anisotropy metrics and cell area fraction. In the clinical study, the diffusivity from IVIM-Kurtosis was the only metric showing significant differences between benign (0.80 ± 0.30 µm2 /ms) and malignant (1.02 ± 0.41 µm2 /ms, P = .03) nodes. IVIM-Kurtosis also yielded the largest area under the receiver operating characteristic curve (0.73) and significantly improved the node differentiation when added to the standard visual analysis by experts based on T2 -weighted imaging. CONCLUSION: Higher-order diffusion MRI models perform better than standard ADC and may be of added value for mesorectal lymph node classification in rectal cancer patients.

Vascular Inflammation in Subclinical Atherosclerosis Detected by Hybrid PET/MRI.

BACKGROUND: Atherosclerosis is a chronic inflammatory disease, but data on arterial inflammation at early stages is limited. OBJECTIVES: The purpose of this study was to characterize vascular inflammation by hybrid 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI). METHODS: Carotid, aortic, and ilio-femoral 18F-FDG PET/MRI was performed in 755 individuals (age 40 to 54 years; 83.7% men) with known plaques detected by 2-/3-dimensional vascular ultrasound and/or coronary calcification in the PESA (Progression of Early Subclinical Atherosclerosis) study. The authors evaluated the presence, distribution, and number of arterial inflammatory foci (increased 18F-FDG uptake) and plaques with or without inflammation (coincident 18F-FDG uptake). RESULTS: Arterial inflammation was present in 48.2% of individuals (24.4% femorals, 19.3% aorta, 15.8% carotids, and 9.3% iliacs) and plaques in 90.1% (73.9% femorals, 55.8% iliacs, and 53.1% carotids). 18F-FDG arterial uptakes and plaques significantly increased with cardiovascular risk factors (p < 0.01). Coincident 18F-FDG uptakes were present in 287 of 2,605 (11%) plaques, and most uptakes were detected in plaque-free arterial segments (459 of 746; 61.5%). Plaque burden, defined by plaque presence, number, and volume, was significantly higher in individuals with arterial inflammation than in those without (p < 0.01). The number of plaques and 18F-FDG uptakes showed a positive albeit weak correlation (r = 0.25; p < 0.001). CONCLUSIONS: Arterial inflammation is highly prevalent in middle-aged individuals with known subclinical atherosclerosis. Large-scale multiterritorial PET/MRI allows characterization of atherosclerosis-related arterial inflammation and demonstrates 18F-FDG uptake in plaque-free arterial segments and, less frequently, within plaques. These findings suggest an arterial inflammatory state at early stages of atherosclerosis. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).

Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity.

BACKGROUND: Anthracycline-induced cardiotoxicity is a major clinical problem, and early cardiotoxicity markers are needed. OBJECTIVES: The purpose of this study was to identify early doxorubicin-induced cardiotoxicity by serial multiparametric cardiac magnetic resonance (CMR) and its pathological correlates in a large animal model. METHODS: Twenty pigs were included. Of these, 5 received 5 biweekly intracoronary doxorubicin doses (0.45 mg/kg/injection) and were followed until sacrifice at 16 weeks. Another 5 pigs received 3 biweekly doxorubicin doses and were followed to 16 weeks. A third group was sacrificed after the third dose. All groups underwent weekly CMR examinations including anatomical and T2 and T1 mapping (including extracellular volume [ECV] quantification). A control group was sacrificed after the initial CMR. RESULTS: The earliest doxorubicin-cardiotoxicity CMR parameter was T2 relaxation-time prolongation at week 6 (2 weeks after the third dose). T1 mapping, ECV, and left ventricular (LV) motion were unaffected. At this early time point, isolated T2 prolongation correlated with intracardiomyocyte edema secondary to vacuolization without extracellular space expansion. Subsequent development of T1 mapping and ECV abnormalities coincided with LV motion defects: LV ejection fraction declined from week 10 (2 weeks after the fifth and final doxorubicin dose). Stopping doxorubicin therapy upon detection of T2 prolongation halted progression to LV motion deterioration and resolved intracardiomyocyte vacuolization, demonstrating that early T2 prolongation occurs at a reversible disease stage. CONCLUSIONS: T2 mapping during treatment identifies intracardiomyocyte edema generation as the earliest marker of anthracycline-induced cardiotoxicity, in the absence of T1 mapping, ECV, or LV motion defects. The occurrence of these changes at a reversible disease stage shows the clinical potential of this CMR marker for tailored anthracycline therapy.

Macrovascular Networks on Contrast-Enhanced Magnetic Resonance Imaging Improves Survival Prediction in Newly Diagnosed Glioblastoma.

A higher degree of angiogenesis is associated with shortened survival in glioblastoma. Feasible morphometric parameters for analyzing vascular networks in brain tumors in clinical practice are lacking. We investigated whether the macrovascular network classified by the number of vessel-like structures (nVS) visible on three-dimensional T1-weighted contrast⁻enhanced (3D-T1CE) magnetic resonance imaging (MRI) could improve survival prediction models for newly diagnosed glioblastoma based on clinical and other imaging features. Ninety-seven consecutive patients (62 men; mean age, 58 ± 15 years) with histologically proven glioblastoma underwent 1.5T-MRI, including anatomical, diffusion-weighted, dynamic susceptibility contrast perfusion, and 3D-T1CE sequences after 0.1 mmol/kg gadobutrol. We assessed nVS related to the tumor on 1-mm isovoxel 3D-T1CE images, and relative cerebral blood volume, relative cerebral flow volume (rCBF), delay mean time, and apparent diffusion coefficient in volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter. We also assessed Visually Accessible Rembrandt Images scoring system features. We used ROC curves to determine the cutoff for nVS and univariate and multivariate cox proportional hazards regression for overall survival. Prognostic factors were evaluated by Kaplan-Meier survival and ROC analyses. Lesions with nVS > 5 were classified as having highly developed macrovascular network; 58 (60.4%) tumors had highly developed macrovascular network. Patients with highly developed macrovascular network were older, had higher volumeCEL, increased rCBFCEL, and poor survival; nVS correlated negatively with survival (r = -0.286; p = 0.008). On multivariate analysis, standard treatment, age at diagnosis, and macrovascular network best predicted survival at 1 year (AUC 0.901, 83.3% sensitivity, 93.3% specificity, 96.2% PPV, 73.7% NPV). Contrast-enhanced MRI macrovascular network improves survival prediction in newly diagnosed glioblastoma.

Prognostic Nutritional Index predicts morbidity after curative surgery for colorectal cancer. / El Prognostic Nutritional Index predice la morbilidad postoperatoria tras la cirugía curativa del cáncer colorrectal.

INTRODUCTION: Colorectal cancer (CRC) is a major health concern and it is associated with significant morbidity and mortality. Over the last decades, the relationship between cancer and nutritional and inflammatory status in oncologic patients was studied thoroughly and multiple immunonutritional scores were developed. These scores have been mainly related to the prognosis of several cancers. An interaction between the tumour and the host is generated, triggering a systemic inflammatory reaction leading to several neuroendocrine changes. This situation favours a tendency towards anorexia and catabolism. Our hypothesis is that nutritional and inflammatory status of oncologic patients is correlated to postoperative morbidity. METHODS: This is a prospective observational cohort study with those patients undergoing curative surgery for CRC at our institution between September 2015 and March 2017. Nutritional and inflammatory status was established using Onodera's Prognostic Nutritional Index (PNI). Complications (overall, severe, infectious and anastomotic leakage) were carefully collected during the first 30 days of the postoperative period. RESULTS: After carrying out the multivariate analysis, PNI turned out to be a great predictive and protective factor for overall complications (RR: 0.279; 95% CI: 0.141-0.552), severe complications (RR: 0.355; 95% CI: 0.130-0.965), infectious complications (RR: 0.220; 95% CI: 0.099-0.489) and anastomotic leakage (RR: 0.151; 95% CI: 0.036-0.640). CONCLUSION: Our work reports that PNI is an independent predictive factor for the development of postoperative complications following curative surgery for CRC.

A new dimensional-reducing variable obtained from original inflammatory scores is highly associated to morbidity after curative surgery for colorectal cancer.

PURPOSE: Several scores have been developed to define the inflammatory status of oncological patients. We suspect they share iterative information. Our hypothesis is that we may summarise their information into one or two new variables which will be independent. This will help us to predict, more accurately, which patients are at an increased risk of suffering postoperative complications after curative surgery for CRC. METHODS: Observational prospective study with those patients undergoing curative surgery for CRC between September 2015 and February 2017. We analysed the influence of inflammatory scores (PNI, GPS, NLR, PLR) on postoperative morbidity (overall and severe complications, anastomotic leakage and reoperation). RESULTS: Finally, 168 patients were analysed. We checked these four original scores are interrelated among them. Using a complex and innovative statistical method, we created two new independent variables (resultant A and resultant B) which resume the information coming from them. One of these two new variables (resultant A) was statistically associated to overall complications (OR, 2.239; 95% CI, 1.541-3.253; p = 0.0001), severe complications (OR, 1.773; 95% CI, 1.129-2.785; p = 0.013), anastomotic leakage (OR, 3.208; 95% CI, 1.416-7.268; p = 0.005) and reoperation (OR, 2.349; 95% CI, 1.281-4.305; p = 0.006). CONCLUSIONS: We evinced the four original scores we used share redundant information. We created two new independent new variables which resume their information. In our sample of patients, one of these variables turned out to be a great predictive factor for the four complications we analysed.

Transplantation of Allogeneic Pericytes Improves Myocardial Vascularization and Reduces Interstitial Fibrosis in a Swine Model of Reperfused Acute Myocardial Infarction.

BACKGROUND: Transplantation of adventitial pericytes (APCs) promotes cardiac repair in murine models of myocardial infarction. The aim of present study was to confirm the benefit of APC therapy in a large animal model. METHODS AND RESULTS: We performed a blind, randomized, placebo-controlled APC therapy trial in a swine model of reperfused myocardial infarction. A first study used human APCs (hAPCs) from patients undergoing coronary artery bypass graft surgery. A second study used allogeneic swine APCs (sAPCs). Primary end points were (1) ejection fraction as assessed by cardiac magnetic resonance imaging and (2) myocardial vascularization and fibrosis as determined by immunohistochemistry. Transplantation of hAPCs reduced fibrosis but failed to improve the other efficacy end points. Incompatibility of the xenogeneic model was suggested by the occurrence of a cytotoxic response following in vitro challenge of hAPCs with swine spleen lymphocytes and the failure to retrieve hAPCs in transplanted hearts. We next considered sAPCs as an alternative. Flow cytometry, immunocytochemistry, and functional/cytotoxic assays indicate that sAPCs are a surrogate of hAPCs. Transplantation of allogeneic sAPCs benefited capillary density and fibrosis but did not improve cardiac magnetic resonance imaging indices of contractility. Transplanted cells were detected in the border zone. CONCLUSIONS: Immunologic barriers limit the applicability of a xenogeneic swine model to assess hAPC efficacy. On the other hand, we newly show that transplantation of allogeneic sAPCs is feasible, safe, and immunologically acceptable. The approach induces proangiogenic and antifibrotic benefits, though these effects were not enough to result in functional improvements.

Preoperative platelet-lymphocyte ratio is an independent factor of poor prognosis after curative surgery for colon cancer.

Interaction between tumour and host triggers a systemic inflammatory response. This situation has been associated to cancer progression. Several peripheral blood inflammatory scores have been recently developed, as PLR. Data about the relationship between these scores and cancer prognosis are contradictory. Therefore, the aim of our work is to evaluate the capability of PLR to predict long-term outcomes (OS and RFS) in patients who underwent curative surgery for colon cancer. A retrospective study was designed with patients who underwent curative surgery for colon cancer between September 2008 and January 2012 at Rio Hortega University Hospital, Valladolid (Spain). We analysed the influence of PLR and other clinical variables on OS and RFS. Finally, 201 patients were analysed. Optimal cut-off value for PLR, established with ROC curves, was 153. 1-, 3- and 5-year OS were: 99.0, 90.4 and 82.3% for low PLR, and 93.8, 74.9 and 61.9% for high PLR, p < 0.001. 1-, 3- and 5-year RFS were: 92.4, 84.7 and 77.6% for low PLR, and 83.3, 64.5 and 52.6% for high PLR, p < 0.001. In MVA, high PLR was an independent negative prognostic factor for OS (HR = 2.11; 95% CI 1.22-3.66; p = 0.008) and RFS (HR = 1.99; 95% CI 1.19-3.34; p = 0.009). PLR represents an independent negative prognostic factor for OS and RFS in our sample of patients who underwent curative surgery for colon cancer. However, further studies with a larger sample size from different populations are necessary to confirm this conclusion.