Risk factors for lymphedema after breast surgery: A prospective cohort study in the era of sentinel lymph node biopsy.

INTRODUCTION: The Objective was to investigate the incidence of lymphedema after breast cancer treatment and to analyze the risk factors involved in a tertiary level hospital. METHODS: Prospective longitudinal observational study over 3 years post-breast surgery. 232 patients undergoing surgery for breast cancer at our institution between September 2013 and February 2018. Sentinel lymph node biopsy (SLNB) or axillary lymphadenectomy (ALND) were mandatory in this cohort. In total, 201 patients met the inclusion criteria and had a median follow-up of 31 months (range, 1-54 months). Lymphedema was diagnosed by circumferential measurements and truncated cone calculations. Patients and tumor characteristics, shoulder range of motion limitation and local and systemic therapies were analyzed as possible risk factors for lymphedema. RESULTS: Most cases of lymphedema appeared in the first 2 years. 13.9% of patients developed lymphedema: 31% after ALND and 4.6% after SLNB (p < 0.01), and 46.7% after mastectomy and 11.3% after breast-conserving surgery (p < 0.01). The lymphedema rate increased when axillary radiotherapy (RT) was added to radical surgery: 4.3% for SLNB alone, 6.7% for SLNB + RT, 17.6% for ALND alone, and 35.2% for ALND + RT (p < 0.01). In the multivariate analysis, the only risk factors associated with the development of lymphedema were ALND and mastectomy, which had hazard ratios (95% confidence intervals) of 7.28 (2.92-18.16) and 3.9 (1.60-9.49) respectively. CONCLUSIONS: The main risk factors for lymphedema were the more radical surgeries (ALND and mastectomy). The risk associated with these procedures appeared to be worsened by the addition of axillary radiotherapy. A follow-up protocol in patients with ALND lasting at least two years, in which special attention is paid to these risk factors, is necessary to guarantee a comprehensive control of lymphedema that provides early detection and treatment.

GEIS-SEHOP clinical practice guidelines for the treatment of rhabdomyosarcoma.

Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma (STS) in children and adolescents. In Spain the annual incidence is 4.4 cases per million children < 14 years. It is an uncommon neoplasm in adults, but 40% of RMS are diagnosed in patients over 20 years of age, representing 1% of all STS in this age group. RMS can appear anywhere in the body, with some sites more frequently affected including head and neck, genitourinary system and limbs. Assessment of a patient with suspicion of RMS includes imaging studies (MRI, CT, PET-CT) and biopsy. All patients with RMS should receive chemotherapy, either at diagnosis in advanced or metastatic stages, or after initial resection in early local stages. Local control includes surgery and/or radiotherapy depending on site, stage, histology and response to chemotherapy. This guide provides recommendations for diagnosis, staging and treatment of this neoplasm.

The paediatric cancer clinical research landscape in Spain: a 13-year multicentre experience of the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

PURPOSE: Early phase trials are crucial in developing innovative effective agents for childhood malignancies. We report the activity in early phase paediatric oncology trials in Spain from its beginning to the present time and incorporate longitudinal data to evaluate the trends in trial characteristics and recruitment rates. METHODS: Members of SEHOP were contacted to obtain information about the open trials at their institutions. The study period was split into two equal periods for analysis: 2007-2013 and 2014-2020. RESULTS: Eighty-one trials and two molecular platforms have been initiated. The number of trials has increased over the time of the study for all tumour types, with a predominance of trials available for solid tumours (66%). The number of trials addressed to tumours harbouring specific molecular alterations has doubled during the second period. The proportion of industry-sponsored compared to academic trials has increased over the same years. A total of 565 children and adolescents were included, with an increasing trend over the study period. For international trials, the median time between the first country study approval and the Spanish competent authority approval was 2 months (IQR 0-6.5). Fourteen out of 81 trials were sponsored by Spanish academic institutions. CONCLUSIONS: The number of available trials, and the number of participating patients, has increased in Spain from 2007. Studies focused on molecular-specific targets are now being implemented. Barriers to accessing new drugs for all ranges of age and cancer diseases remain. Additionally, opportunities to improve academic research are still required in Spain.

An ab initio study of the magnetic properties of strontium hexaferrite.

The magnetic properties of [Formula: see text], a paradigmatic hexaferrite for permanent magnet applications, have been addressed in detail combining density functional theory including spin-orbit coupling and a Hubbard U term with Monte Carlo simulations. This multiscale approach allows to estimate the Néel temperature of the material from ab initio exchange constants, and to determine the influence of different computational conditions on the magnetic properties by direct comparison versus available experimental data. It is found that the dominant influence arises from the choice of the Hubbard U term, with a value in the 2-3 eV range as the most adequate to quantitatively reproduce the two most relevant magnetic properties of this material, namely: its large perpendicular magnetocrystalline anisotropy and its elevated Néel temperature.

[Facial and labial lymphedema after oncological treatment. A propos of clinical case]. / Linfedema facial y labial secundario a tratamiento oncológico. A propósito de un caso clínico.

Facial lymphedema secondary to treatment by a neoplastic process is a rare and disabling pathology, causing functional and aesthetic alterations. A case report of facial and labial lymphedema describing the functional repercussion and aesthetic defect. We present a 61-years-old female patient suffered a tongue neoplasia and bilateral cervical lymphadenectomy in 2015. After several treatments, including diverse surgical interventions and adjuvant radiotherapy, developed facial and labial lymphedema. The patient was sent to our Rehabilitation Department complaining about swelling of the face and lips, dysphagia, sialorrhea, xerostomia, dysarthria and decubitus in lower lip by labia protusion. Due to the functional repercussion that it caused in the patient, rehabilitating physical treatment was planned with manual lymph drainage, facial silicone orthosis and lymphatic taping. The patient improved both subjectively as well as objectively in terms of hardness, volume and slight improvement of lip lymphedema.

Qualitative disorder measurements from backscattering spectra through an optical fiber.

In the processes related to the development of cancer, there are different genetic and epigenetic events involved that result in structural changes of the affected cells. In the early stages of the disease, these changes occur at the nanoscale, remaining undetectable by conventional light microscopy, due to diffraction-limited resolution (∼250 - 550 nm). In this sense, a technique termed partial wave spectroscopy (PWS) allows the detection of these nanostructural changes by measuring a statistical parameter called disorder strength (L d ). PWS uses a combination of a tunable filter and a camera to acquire the backscattering spectra for each pixel on the image. In this paper, we study and validate the possibility of obtaining a qualitative measurement of the disorder using the spectrum of the averaged spatial information. Instead of using spatial information and measuring sequentially spectral ranges, we measure the backscattered signal gathered by an optical fiber by means of a spectrograph. This will allow this method to be applied in systems where it is not possible to acquire a complete high resolution image for many spectral bands, while significantly enhancing speed.

miRNA-7 and miRNA-324-5p regulate alpha9-Integrin expression and exert anti-oncogenic effects in rhabdomyosarcoma.

The prognosis of patients with metastatic rhabdomyosarcoma (RMS), the most common type of soft tissue sarcoma in children, is poor and no strategies have been identified to improve their dismal prognosis. Alpha-9 integrin (ITGA9) plays a particularly crucial role in cancer progression and invasiveness. Despite the consensus on the remarkable pro-oncogenic potential of this protein, the miRNA-mediated regulation of ITGA9 has barely been studied to date. In the present study, miR-7 and miR-324-5p were selected as the best candidates after a screening to find ITGA9 regulators, and their effects on cell proliferation and invasion in RMS are described and characterized for the first time. Interestingly, the overexpression of both miRNA produced a clear impairment of cell proliferation, while miR-7 also induced a remarkable drop in cell invasion. Furthermore, the stable overexpression of both miRNA was found to reduce tumor growth in orthotopic RMS models and miR-7 was able to impair metastatic lung colonization. Consequently, we conclude that miR-7 and miR-324-5p show anti-oncogenic and anti-metastatic potential, thereby opening up the possibility of being used as novel therapeutic tools to avoid RMS progression.

ECLIM-SEHOP, a new platform to set up and develop international academic clinical trials for childhood cancer and blood disorders in Spain.

INTRODUCTION: Cancer and blood disorders in children are rare. The progressive improvement in survival over the last decades largely relies on the development of international academic clinical trials that gather the sufficient number of patients globally to elaborate solid conclusions and drive changes in clinical practice. The participation of Spain into large international academic trials has traditionally lagged behind of other European countries, mainly due to the burden of administrative tasks to open new studies, lack of financial support and limited research infrastructure in our hospitals. METHODS: The objective of ECLIM-SEHOP platform (Ensayos Clínicos Internacionales Multicéntricos-SEHOP) is to overcome these difficulties and position Spain among the European countries leading the advances in cancer and blood disorders, facilitate the access of our patients to novel diagnostic and therapeutic approaches and, most importantly, continue to improve survival and reducing long-term sequelae. ECLIM-SEHOP provides to the Spanish clinical investigators with the necessary infrastructural support to open and implement academic clinical trials and registries. RESULTS: In less than 3 years from its inception, the platform has provided support to 20 clinical trials and 8 observational studies, including 8 trials and 4 observational studies where the platform performs all trial-related tasks (integral support: trial setup, monitoring, etc.) with more than 150 patients recruited since 2017 to these studies. In this manuscript, we provide baseline metrics for academic clinical trial performance that permit future comparisons. CONCLUSIONS: ECLIM-SEHOP facilitates Spanish children and adolescents diagnosed with cancer and blood disorders to access state-of-the-art diagnostic and therapeutic strategies.

Strontium hexaferrite platelets: a comprehensive soft X-ray absorption and Mössbauer spectroscopy study.

Platelets of strontium hexaferrite (SrFe12O19, SFO), up to several micrometers in width, and tens of nanometers thick have been synthesized by a hydrothermal method. They have been studied by a combination of structural and magnetic techniques, with emphasis on Mössbauer spectroscopy and X-ray absorption based-measurements including spectroscopy and microscopy on the iron-L edges and the oxygen-K edge, allowing us to establish the differences and similarities between our synthesized nanostructures and commercial powders. The Mössbauer spectra reveal a greater contribution of iron tetrahedral sites in platelets in comparison to pure bulk material. For reference, high-resolution absorption and dichroic spectra have also been measured both from the platelets and from pure bulk material. The O-K edge has been reproduced by density functional theory calculations. Out-of-plane domains were observed with 180° domain walls less than 20 nm width, in good agreement with micromagnetic simulations.

Holographic waveguides in photopolymers.

The possibilities that offer the holographic optical elements for photovoltaic and "see through display" applications open new windows for holographic recording materials. In this sense, some specific characteristics are required for each particular application. Waveguides are one of the key elements for these applications. Photopolymers are one of the most competitive candidates for waveguide fabrication. In this work, we evaluate the performance of one example from each of three families of photopolymer material in fabrication of a 633nm waveguide. Firstly, polyvinyl alcohol acrylamide, PVA/AA, the second one, a nanoparticle-thiol-ene, NPC, and on the last place a penta/hexa-acrylate based polymer with dispersed nematic liquid crystal molecules, PDLC. We study the critical role of the material and in particular, spatial resolution for this application.

[Evolution of the incidence of colonized and infected patients by VIM carbapenemase-producing bacteria in a pediatric hospital in Spain]. / Evolución de la incidencia de pacientes con colonización e infección por bacterias productoras de carbapenemasas VIM en un hospital pediátrico en España.

OBJECTIVE: The aim of this study is to describe the evolution of the incidence of infected and colonized patients with carbapenemase VIM-producing bacteria (CPB-VIM) at a national referral pediatric center in Madrid, Spain, between 2012 and 2015. METHODS: Descriptive epidemiological surveillance study. The surveillance system included case detection (screening for BPC colonization in all admitted patients, with periodicity according to the ward) and control measures (contact precautions, identification of previously colonized patients at admission, environmental cleaning, education, supervision of contact precautions, and patient cohort). All hospitalized patients with first positive microbiological sample for CPB-VIM in 2012-2015 were included. Colonized patients were followed through clinical history to evaluate later infection. RESULTS: We found 239 colonized and 51 infected patients with CPB-VIM (49.3% women, 47.6% were 5 months old or younger, 52.1% admitted at Intensive Care Unit). Infection and colonization incidence were, respectively, 2.6 and 6.7 cases per one thousand hospitalized patients in 2012, 1.8 and 10.0 in 2014 and 0.3 and 5.0 in 2015. Within these patients, 84.4% shared ward with other patient with previous positive sample. 13.0% (31/239) of colonized patients had a subsequent infection. CONCLUSIONS: We have shown data of pediatric patients affected by BPC-VIM, collected from an epidemiological surveillance system that included systematic screening at a national referral center. After an epidemic period, the incidence of cases went down. The surveillance and infection control measures intensification, as well as coordination with involved departments, were key in the handling of the situation.

Control of endemic multidrug-resistant Gram-negative bacteria after removal of sinks and implementing a new water-safe policy in an intensive care unit.

BACKGROUND: Contaminated handwashing sinks have been identified as reservoirs that can facilitate colonization/infection of patients with multidrug-resistant (MDR) Gram-negative bacteria (GNB) in intensive care units (ICUs). AIM: To assess the impact of removing patients' sinks and implementing other water-safe strategies on the annual rates of ICU-acquired MDR-GNB. METHODS: This six-year quasi-experimental study was conducted from January 2011 to December 2016. The intervention was carried out in August 2014 in two adult ICU wards with 12 rooms each. To assess the changes in annual MDR-GNB rates before and after the intervention, we used segmented regression analysis of an interrupted time-series. Crude relative risk (RR) rates were also calculated. FINDINGS: The incidence rates of MDR-GNB were 9.15 and 2.20 per 1000 patient-days in the pre- and post-intervention periods, respectively. This yielded a crude RR of acquiring MDR-GNB of 0.24 (95% confidence interval: 0.17-0.34). A significant change in level was observed between the MDR-GNB rate at the first point of the post-intervention period and the rate predicted by the pre-intervention time trend. CONCLUSION: The implementation of a new water-safe policy, which included the removal of sinks from all patient rooms, successfully improved the control of MDR-GNB spread in an ICU with endemic infection. Our results support the contribution of sink use with the incidence of MDR-GNB in endemic environments.

Ligand-dependent Hedgehog pathway activation in Rhabdomyosarcoma: the oncogenic role of the ligands.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children. The Hedgehog (HH) pathway is known to develop an oncogenic role in RMS. However, the molecular mechanism that drives activation of the pathway in RMS is not well understood. METHODS: The expression of HH ligands was studied by qPCR, western blot and immunohistochemistry. Functional and animal model studies were carried out with cells transduced with shRNAs against HH ligands or treated with HH-specific inhibitors (Vismodegib and MEDI-5304). Finally, the molecular characterisation of an off-target effect of Vismodegib was also made. RESULTS: The results showed a prominent expression of HH ligands supporting an autocrine ligand-dependent activation of the pathway. A comparison of pharmacologic Smoothened inhibition (Vismodegib) and HH ligand blocking (MEDI-5304) is also provided. Interestingly, a first description of pernicious off-target effect of Vismodegib is also reported. CONCLUSIONS: The clarification of the HH pathway activation mechanism in RMS opens a door for targeted therapies against HH ligands as a possible alternative in the future development of better treatment protocols. Moreover, the description of a pernicious off-target effect of Vismodegib, via unfolded protein response activation, may mechanistically explain its previously reported inefficiency in several ligand-dependent cancers.

Fluoride-promoted carbonylation polymerization: a facile step-growth technique to polycarbonates.

Fluoride-Promoted Carbonylation (FPC) polymerization is herein presented as a novel catalytic polymerization methodology that complements ROP and unlocks a greater synthetic window to advanced polycarbonates. The overall two-step strategy is facile, robust and capitalizes on the synthesis and step-growth polymerization of bis-carbonylimidazolide and diol monomers of 1,3- or higher configurations. Cesium fluoride (CsF) is identified as an efficient catalyst and the bis-carbonylimidazolide monomers are synthesized as bench-stable white solids, easily obtained on 50-100 g scales from their parent diols using cheap commercial 1,1'-carbonyldiimidazole (CDI) as activating reagent. The FPC polymerization works well in both solution and bulk, does not require any stoichiometric additives or complex settings and produces only imidazole as a relatively low-toxicity by-product. As a proof-of-concept using only four diol building-blocks, FPC methodology enabled the synthesis of a unique library of polycarbonates covering (i) rigid, flexible and reactive PC backbones, (ii) molecular weights 5-20 kg mol-1, (iii) dispersities of 1.3-2.9 and (iv) a wide span of glass transition temperatures, from -45 up to 169 °C.

VIM-Klebsiella oxytoca outbreak in a Neonatal Intensive Care Unit. This time it wasn't the drain.

OBJECTIVE: We describe an outbreak of VIM-carbapenemase Klebsiella oxytoca (VIM-Kox) in a NICU. MATERIALS AND METHODS: Prospective Epidemiological Surveillance:Systematically (weekly screening cultures) or on admission, if the patient had a history of previous colonization by VIM-Kox.Clinical cultures, done if infection was suspected.Other possible microorganism sources were investigated: their mothers (rectal microbiota), milk packages and preparation apparata in the lactodietary section, echocardiagram transductors, cribs, the sinks (faucets and drains), washing bowls, etc.Molecular typing was performed using the DiversiLab (bioMérieux) system on all VIM-Kox isolated from environment or patients (one by neonate). RESULTS: We identified 20 VIM-Kox cases, the most only presented colonization, but 4 showed infection. Three of the ten sinks (drains) in our NICU, were positive for VIM-Kox. Another four drains harbored P.aeruginosa, S. maltophilia and/or Enterobacter sp. Nevertheless the VIM-Kox bacteria in the sinks (drains) were not the same as those in the patients, who showed three different strains. CONCLUSIONS: A VIM-Kox colonization or infection outbreak in a NICU is described. Rather than environment, not even drains, the source of the outbreak was other patients. The outbreak was relatively brief, as a result of the rapidness with which appropriate measures were taken and followed.

Patient-derived xenografts for childhood solid tumors: a valuable tool to test new drugs and personalize treatments.

The use of preclinical models is essential in translational cancer research and especially important in pediatric cancer given the low incidence of each particular type of cancer. Cell line cultures have led to significant advances in cancer biology. However, cell lines have adapted to growth in artificial culture conditions, thereby undergoing genetic and phenotypic changes which may hinder the translational application. Tumor grafts developed in mice from patient tumor tissues, generally known as patient-derived xenografts (PDXs), are interesting alternative approaches to reproducing the biology of the original tumor. This review is focused on highlighting the interest of PDX models in pediatric cancer research and supporting strategies of personalized medicine. This review provides: (1) a description of the background of PDX in cancer, (2) the particular case of PDX in pediatric cancer, (3) how PDX can improve personalized medicine strategies, (4) new methods to increase engraftment, and, finally, (5) concluding remarks.

Symmetry conditions for type II multiferroicity in commensurate magnetic structures.

Type II multiferroics are magnetically ordered phases that exhibit ferroelectricity as a magnetic induced effect. We show that in single-k magnetic phases the presence in the paramagnetic phase of non-symmorphic symmetry combined with some specific type of magnetic propagation vector can be sufficient for the occurrence of this type of multiferroic behaviour. Other symmetry scenarios especially favourable for spin driven multiferroicity are also presented. We review and classify known type II multiferroics under this viewpoint. In addition, some other magnetic phases which due to their symmetry properties can exhibit type II multiferroicity are pointed out.

BRG1/SMARCA4 is essential for neuroblastoma cell viability through modulation of cell death and survival pathways.

Neuroblastoma (NB) is a neoplasm of the sympathetic nervous system, and is the most common solid tumor of infancy. NBs are very heterogeneous, with a clinical course ranging from spontaneous regression to resistance to all current forms of treatment. High-risk patients need intense chemotherapy, and only 30-40% will be cured. Relapsed or metastatic tumors acquire multi-drug resistance, raising the need for alternative treatments. Owing to the diverse mechanisms that are responsible of NB chemoresistance, we aimed to target epigenetic factors that control multiple pathways to bypass therapy resistance. We found that the SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4/BRG1) was consistently upregulated in advanced stages of NB, with high BRG1 levels being indicative of poor outcome. Loss-of-function experiments in vitro and in vivo showed that BRG1 is essential for the proliferation of NB cells. Furthermore, whole-genome transcriptome analysis revealed that BRG1 controls the expression of key elements of oncogenic pathways such as PI3K/AKT and BCL2, which offers a promising new combination therapy for high-risk NB.

Diffractive lenses recorded in absorbent photopolymers.

Photopolymers can be appealing materials for diffractive optical elements fabrication. In this paper, we present the recording of diffractive lenses in PVA/AA (Polyvinyl alcohol acrylamide) based photopolymers using a liquid crystal device as a master. In addition, we study the viability of using a diffusion model to simulate the lens formation in the material and to study the influence of the different parameters that govern the diffractive formation in photopolymers. Once we control the influence of each parameter, we can fit an optimum recording schedule to record each different diffractive optical element with the optimum focalization power.

Experimental evaluation of neutron dose in radiotherapy patients: Which dose?

PURPOSE: The evaluation of peripheral dose has become a relevant issue recently, in particular, the contribution of secondary neutrons. However, after the revision of the Recommendations of the International Commission on Radiological Protection, there has been a lack of experimental procedure for its evaluation. Specifically, the problem comes from the replacement of organ dose equivalent by the organ-equivalent dose, being the latter "immeasurable" by definition. Therefore, dose equivalent has to be still used although it needs the calculation of the radiation quality factor Q, which depends on the unrestricted linear energy transfer, for the specific neutron irradiation conditions. On the other hand, equivalent dose is computed through the radiation weighting factor wR, which can be easily calculated using the continuous function provided by the recommendations. The aim of the paper is to compare the dose equivalent evaluated following the definition, that is, using Q, with the values obtained by replacing the quality factor with wR. METHODS: Dose equivalents were estimated in selected points inside a phantom. Two types of medical environments were chosen for the irradiations: a photon- and a proton-therapy facility. For the estimation of dose equivalent, a poly-allyl-diglicol-carbonate-based neutron dosimeter was used for neutron fluence measurements and, additionally, Monte Carlo simulations were performed to obtain the energy spectrum of the fluence in each point. RESULTS: The main contribution to dose equivalent comes from neutrons with energy higher than 0.1 MeV, even when they represent the smallest contribution in fluence. For this range of energy, the radiation quality factor and the radiation weighting factor are approximately equal. Then, dose equivalents evaluated using both factors are compatible, with differences below 12%. CONCLUSIONS: Quality factor can be replaced by the radiation weighting factor in the evaluation of dose equivalent in radiotherapy environments simplifying the practical procedure.