Social robotics as an adjuvant during the hospitalization process in pediatric oncology patients.

OBJECTIVE: To describe the experience of implementing social robotics as an adjuvant during the hospitalization process in pediatric oncology patients. METHODS: Before and after cohort study, applying an intervention with the Lego Mindstorms EV3 kit in patients between 8 and 17 years old that are hospitalized with a cancer diagnosis. We excluded patients from the intensive care unit or when their treating physician recommended so. The intervention consisted of a three-phase workshop: an open architecture story, building a car robot using the Lego Mindstorm EV3 kit, and cooperative playing activities such as races and passing obstacles. RESULTS: Thirteen patients received the intervention with robotic lego. The median age was 15 years (IQR = 3), and 84.6% of the population (n = 11) were male. We found significant improvement in the language (topic management p = .011 and communicative intention p = .034). Other characteristics improved, but not significantly (self-care activities index, catching). No adverse events occurred during the intervention. CONCLUSIONS: The results of this pilot study suggest that implementing social robotics during hospitalization in children with cancer is a therapeutic adjuvant and safe intervention that promotes better communication, self-care, and a physical activity improvement. For future studies, the impact of this intervention could be measured in hospitalized pediatric cancer patients.

Education by a social robot on nutrition and catheter care in pediatric oncology patients.

PURPOSE: To improve knowledge on nutrition and catheter care in children with cancer by an educational intervention with a social robot. METHODS: We conducted a cohort study on pediatric cancer patients in a high complexity Hospital in Bogotá, Colombia. We included 14 patients (8-17 years old) who underwent an educational intervention with the help of a humanoid robot (Nao V6). The robot was programmed to transmit educational messages about self-care in feeding and using the central venous catheter. A survey with yes-no questions was administered before and after the intervention. RESULTS: We found an improvement in understanding of the subject matter related to nutrition and catheter care, when comparing the knowledge on topics before and after the educational intervention (p < .001). CONCLUSION: Education by a social robot on nutrition and catheter care showed a positive effect on children's knowledge on these topics. Therefore, it potentially decreases the risk of poor feeding habits and inadequate central venous catheter management, and improves adherence to recommendations and quality of life.

N-Acetylcistein for thrombotic thrombocytopenic purpura: an observational case series study.

Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder. N-Acetylcysteine (NAC) rapidly degrades ultra-large von Willebrand factor multimers by disrupting the disulfide bonds. We report a series of twelve consecutive patients diagnosed with acquired TTP successfully treated with high-dose NAC (150 mg/kg/day) in combination with plasma exchange and steroids. Eight patients also received rituximab. Two patients presented refractory TTP. All patients achieved a quick clinical response in a median time of 5.5 days after starting NAC and are alive after a median follow-up of 29 months. The treatment was feasible and well tolerated. These data provide further evidence of the potential benefit and safety of adding NAC to the standard of care.

¿Psicosis luego de sobredosis por opioides? Lesión isquémica bilateral del globo pálido como causa orgánica insospechada / ¿Psychosis after opioid overdose? Bilateral globus pallidus ischaemic injury as an unsuspected organic cause

RESUMEN El abordaje de pacientes intoxicados que presentan antecedentes de patología psiquiátrica supone un reto en la atención médica. La presencia de una patología dual puede conducir a que algunos síntomas somáticos sean desestimados y no se consideren como manifestación de una posible patología grave subyacente. Se reporta el caso de una paciente que, durante su hospitalización debida a un episodio depresivo, presentó una sobredosis incidental de opioides. Al recuperarse de ella, sin embargo, presentó comportamiento desorganizado e ideas delirantes, inicialmente atribuidas a la depresión. Estudios ulteriores demostraron una causa orgánica grave subyacente: lesión isquémica bilateral del globo pálido. Se analiza el cuadro clínico a la luz de la literatura pertinente, abordando los temas de delirium, espectro clínico debido a las lesiones del globo pálido y finalizando con una breve descripción sobre la sobredosis y neurotoxicidad por opioides. Frente a síntomas no concordantes con la evolución usual de una descompensación psicopatológica o una intoxicación por drogas, debe ahondarse en la exploración de posibles causas orgánicas, objetivo para el cual se sugiere considerar estudios de neuroimágenes en todo paciente que experimente una sobredosis de opioides y que posteriormente presente graves manifestaciones de una alteración cognitiva.

SUMMARY The approach to intoxicated patients with a previous history of psychopathological manifestations represents a challenge to medical care. The presence of a dual pathology can lead to somatic symptoms being dismissed and not considered as possible manifestations of a serious underlying pathology. We report the case of a patient who, during her hospitalization for a depressive episode, presented an incidental opioid overdose. Upon recovery, she presented disorganized behavior and delusions, initially attributed to her depression. Further studies demonstrated, however, a serious underlying organic cause: A bilateral ischaemic injury of the globus pallidus. The clinical picture is analyzed in the light of the relevant literature, addressing the issues of delirium, clinical spectrum of globus pallidus lesions and ending with a brief description of opioid overdoses and neurotoxicity. Faced with symptoms that are not consistent with the usual course of a psychopathological decompensation or drug intoxication, possible organic causes should be delved into. It is suggested that neuroimaging studies be considered in any patient who suffers from an opioid overdose and who later presents severe cognitive alterations.

Near-Room-Temperature Magnetoelectric Coupling via Spin Crossover in an Iron(II) Complex.

Magnetoelectric coupling is achieved near room temperature in a spin crossover FeII molecule-based compound, [Fe(1bpp)2 ](BF4 )2 . Large atomic displacements resulting from Jahn-Teller distortions induce a change in the molecule dipole moment when switching between high-spin and low-spin states leading to a step-wise change in the electric polarization and dielectric constant. For temperatures in the region of bistability, the changes in magnetic and electrical properties are induced with a remarkably low magnetic field of 3 T. This result represents a successful expansion of magnetoelectric spin crossovers towards ambient conditions. Moreover, the observed 0.3-0.4 mC m-2 changes in the H-induced electric polarization suggest that the high strength of the coupling obtained via this route is accessible not just at cryogenic temperatures but also near room temperature, a feature that is especially appealing in the light of practical applications.

Promoters of ASCL1- and NEUROD1-dependent genes are specific targets of lurbinectedin in SCLC cells.

Small-Cell Lung Cancer (SCLC) is an aggressive neuroendocrine malignancy with a poor prognosis. Here, we focus on the neuroendocrine SCLC subtypes, SCLC-A and SCLC-N, whose transcription addiction was driven by ASCL1 and NEUROD1 transcription factors which target E-box motifs to activate up to 40% of total genes, the promoters of which are maintained in a steadily open chromatin environment according to ATAC and H3K27Ac signatures. This leverage is used by the marine agent lurbinectedin, which preferentially targets the CpG islands located downstream of the transcription start site, thus arresting elongating RNAPII and promoting its degradation. This abrogates the expression of ASCL1 and NEUROD1 and of their dependent genes, such as BCL2, INSM1, MYC, and AURKA, which are responsible for relevant SCLC tumorigenic properties such as inhibition of apoptosis and cell survival, as well as for a part of its neuroendocrine features. In summary, we show how the transcription addiction of these cells becomes their Achilles's heel, and how this is effectively exploited by lurbinectedin as a novel SCLC therapeutic endeavor.

Disección espontánea del tronco celíaco. Una emergencia vascular inusual / Spontaneous dissection of the celiac trunk. An unusual vascular emergency

Introducción. La disección espontánea del tronco o arteria celíaca es una emergencia vascular abdominal inusual, con una incidencia desconocida. Actualmente no existen guías o consensos para su tratamiento, el cual va desde intervenciones vasculares mayores hasta la conducta expectante. Caso clínico. Paciente masculino de 42 años sin antecedentes patológicos, con dolor abdominal intenso de un mes de evolución. Ante la sospecha clínica de patología inflamatoria se realizó una tomografía computarizada abdominal con medio de contraste, en la que se observó una disección del tronco celíaco asociada a un infarto esplénico. Se realizó manejo endovascular de forma exitosa. Discusión. La disección espontánea del tronco celíaco es una patología infrecuente, que puede presentarse en pacientes con hipertensión arterial, tabaquismo, enfermedad ateroesclerótica y vasculitis. Los síntomas más comunes son el dolor abdominal asociado a náuseas y vómito. La sospecha clínica debe ser confirmada mediante estudios imagenológicos que orienten al tratamiento conservador, endovascular o quirúrgico, ante la sospecha de infarto intestinal o ruptura arterial. Conclusiones. La disección espontánea del tronco celíaco es una patología vascular inusual que puede relacionarse con una alta mortalidad. Es importante tener siempre presente la interrelación entre la anatomía vascular abdominal, la anamnesis y el examen físico como elementos claves para realizar este diagnóstico.

Introduction. Spontaneous dissection of the celiac artery or trunk is an unusual abdominal vascular emergency, with an unknown incidence. Currently there are no guidelines or consensus for its treatment, which ranges from major vascular interventions to expectant management. Clinical case. A 42-year-old male patient with no medical history, with intense abdominal pain of one month of evolution. Given the clinical suspicion of inflammatory pathology, an abdominal computed tomography with contrast was performed, in which a dissection of the celiac trunk associated with a splenic infarction was observed. Endovascular management was performed successfully. Discussion. Spontaneous dissection of the celiac trunk is an infrequent pathology, which can occur in patients with high blood pressure, smoking, atherosclerotic disease, and vasculitis. The most common symptoms are abdominal pain associated with nausea and vomiting. Clinical suspicion must be confirmed by imaging studies that guide conservative, endovascular or surgical treatment in the event of suspected intestinal infarction or arterial rupture. Conclusions. Spontaneous dissection of the celiac trunk is an unusual vascular pathology that can be associated with high mortality. It is important to always keep in mind the relationship between the abdominal vascular anatomy, anamnesis, and physical examination as key elements in making this diagnosis.

Low-affinity immunoglobulin gamma Fc region receptor III-B (FcγRIIIB, CD16B) deficiency in patients with blood and immune system disorders.

Low-affinity immunoglobulin gamma Fc region receptor III-B (FcγRIIIB) deficiency is present in ˜0·05% of the general population. Among our patients, FcγRIIIB deficiency was less frequent in those with immune-system disorders (one of 1815 patients, 0·05%) than in those with blood disorders (nine of 2147 patients, 0·42%, P = 0·023): mainly primary immune thrombocytopenia (4·34%), therapy related myeloid neoplasms (1·16%) and myelodysplastic syndrome with excess blasts (1·28%). Four of the nine (44·4%) patients with blood disorders were diagnosed with or quickly evolved to acute myeloid leukaemia (AML), suggesting that FcγRIIIB deficiency could be an adverse prognostic factor for progression to AML that should be confirmed in large multicentre studies.

Ataque isquémico transitorio por embolia aérea iatrogénica secundaria a inyecciones intracavernosas en procedimiento urológico / Transient ischemic attack due to iatrogenic air embolism secondary to intracavernous injections during an urologic procedure

RESUMEN Se presenta un caso de ataque isquémico transitorio con sintomatología compatible con lesión de la circulación cerebral posterior, secundario a embolia aérea iatrogénica. Se describe la evolución clínica y las consideraciones más relevantes de la atención y el diagnóstico del ataque cerebrovascular de la circulación posterior. En cuanto a la embolia gaseosa, se describen los métodos diagnósticos, las intervenciones clínicas y las opciones de tratamiento disponibles.

SUMMARY Here ia a case of transient ischemic attack with symptoms compatible with injury to the posterior cerebral circulation, secondary to iatrogenic air embolism. Clinical evolution and the most relevant aspects for the care and diagnosis of cerebrovascular stroke of the posterior circulation are described. Regarding air embolism, the diagnostic methods, clinical interventions, and available treatment options are described.

Specific Effects of Trabectedin and Lurbinectedin on Human Macrophage Function and Fate-Novel Insights.

BACKGROUND: Tumor-associated macrophages (TAMs) play a crucial role in suppressing the immunosurveillance function of the immune system that prevents tumor growth. Indeed, macrophages can also be targeted by different chemotherapeutic agents improving the action over immune checkpoints to fight cancer. Here we describe the effect of trabectedin and lurbinectedin on human macrophage cell viability and function. METHODS: Blood monocytes from healthy donors were differentiated into macrophages and exposed to different stimuli promoting functional polarization and differentiation into tumor-associated macrophages. Cells were challenged with the chemotherapeutic drugs and the effects on cell viability and function were analyzed. RESULTS: Human macrophages exhibit at least two different profiles in response to these drugs. One-fourth of the blood donors assayed (164 individuals) were extremely sensitive to trabectedin and lurbinectedin, which promoted apoptotic cell death. Macrophages from other individuals retained viability but responded to the drugs increasing reactive oxygen production and showing a rapid intracellular calcium rise and a loss of mitochondrial oxygen consumption. Cell-membrane exposure of programmed-death ligand 1 (PD-L1) significantly decreased after treatment with therapeutic doses of these drugs, including changes in the gene expression profile of hypoxia-inducible factor 1 alpha (HIF-1α)-dependent genes, among other. CONCLUSIONS: The results provide evidence of additional onco-therapeutic actions for these drugs.

Brain manifestations secondary to auricular myxoma.

Cardiac myxoma is the most common benign tumor of the heart. In most cases, it is in the left atrium, which can generate neurological embolization; that can manifest as an ischemic event, aneurysm formation and less frequently as brain metastases. This is a case report of a 56-year-old male patient with cerebral embolisms secondary to a left cardiac myxoma. In these patients, the role of neurologic imaging is to detect the firsts complications and avoid secondary complications.

Characterization of plastic beach litter by Raman spectroscopy in South-western Spain.

The characteristics and distribution of plastic litter were evaluated in October 2018 at 40 beaches along the coast of Cádiz Province, in Spain. A total of 14,261 plastic items, appertaining to 57 litter groups, were identified along the study area at different beach zones, i.e. at low tide water level (2%), along the foreshore (6%), at high tide water level (67%) and in the backshore area (25%). Plastic items have a great floatability, being this one of the main reasons for their proportional dominance among beach litter, especially in the wrack line. Hundreds of measurements were made of different items using Raman spectroscopy, an effective technique to determine the type of plastic. Cellulose acetate represented the most abundant material (79%) linked to cigarette butts, followed by polypropylene, 9% and polyethylene, 8%. The remaining were composed by polystyrene, polyethylene terephthalate and polyvinyl chloride. Smoke related items were the most common in the study area, followed by film and hard pieces, cotton bud sticks, fishing strings, food wrappers, caps/lids and single-use plastics. Beach litter can be related to beachgoers but some categories can be attributed to fishing activities or wastewater discharges. Plastics cause a multitude of damages to the coastal ecosystem, due to their toxic components and adsorbed substances and their facility of fragmentation and dispersion. Principal objective is the compositional characterization of plastic beach litter items and their spatial variability. It is therefore important to avoid unnecessary consumption, promote recycling and use other materials that are less harmful to the environment.

Arritmias graves en el síndrome de takotsubo: ¿cuándo dar de alta? / Severe arrhythmias in Takotsubo syndrome: when to discharge?

Resumen El síndrome de takotsubo o miocardiopatía por estrés es una alteración de la funcionalidad miocárdica, que se asocia con frecuencia a situaciones de estrés físico o emocional. Corresponde entre el 1 y el 2% de todos los ingresos a urgencias por síndrome coronario agudo y tiene una prevalencia y tasa de mortalidad de 4,1% y 2% a 8%, respectivamente. Hasta el 10% de los pacientes presenta algún tipo de complicación. En Colombia los datos epidemiológicos son limitados. En la actualidad se desconoce con exactitud la fisiopatología subyacente y no hay consenso acerca del tratamiento del síndrome y las complicaciones asociadas; por consiguiente, estos interrogantes son posibles temas de investigación. Se expone un caso clínico de características inusuales, que cursó con alteraciones electrocardiográficas, cinéticas y de conducción miocárdica infrecuentes, además de evolución clínica inesperada, que culminó en paro cardiorrespiratorio secundario a taquicardia ventricular polimórfica por persistencia del intervalo QT prolongado. Con base en la experiencia clínica y en la evidencia científica disponible se recomienda monitorizar estrechamente a los pacientes con alteración adquirida de la repolarización miocárdica hasta que esta se normalice y considerar la implantación de un dispositivo cardiaco tipo cardiodesfibrilador en casos de alto riesgo.

Abstract Takotsubo syndrome or stress cardiomyopathy is a myocardial functional disorder, which is often associated with situations of physical or emotional stress. It accounts for between 1% and 2% of all those admitted to the Emergency Department due to acute coronary syndrome, and has a prevalence and mortality rate of 4.1% and 2% to 8%, respectively. Up to 10% of the patients have some type of complication. Epidemiological data are scarce in Colombia. The underlying pathophysiology is still not exactly known, and there is no consensus on the treatment of the syndrome and the associated complications. Therefore, these questions are possible research topics. A clinical case of unusual characteristics is presented, which included rare electrocardiographic, kinetic, and myocardial conduction characteristics. It also had an unexpected clinical outcome, which culminated in cardiorespiratory arrest secondary to a polymorphic ventricular tachycardia due to persistence of the prolonged QT interval. Based on clinical experience and on the available scientific evidence, it is recommended to closely monitor patients with an acquired change in myocardial repolarisation until it returns to normal, and to consider an implantable cardioverter defibrillator in cases of high risk.

Diagnosis of rhomboencephalosynapsis by MRI in a 5-year-old child.

Rhombencephalosynapsis is a rare defect in the development of the cerebellum, characterized by partial or total agenesis of the vermis, with fusion of the cerebellar hemispheres in the midline. It is usually related to Gómez-López-Hernández Syndrome (cerebellar-trigeminal dermal dysplasia) and VACTERL association association (vertebral defects, vascular anomalies, anal atresia, cardiac anomalies, tracheoesophageal fistula with esophageal atresia, renal dysplasia and limb anomalies). A 5-year-old female patient with spastic cerebral palsy and hydrocephalus presented here, neuroimages documented the next features: absence of cerebellar vermis, periventricular leukomalacia, cerebellar tonsils descent and rhombencephalosynapsis. Other important imaging findings and associations in these cases are discussed.

Generation of endoplasmic reticulum stress and inhibition of autophagy by plitidepsin induces proteotoxic apoptosis in cancer cells.

Plitidepsin (PLD, Aplidin®), a cyclic depsipeptide originally isolated from the marine tunicate Aplidium albicans, has been recently approved by Australian regulatory authorities for the treatment of multiple myeloma patients. Plitidepsin binds to eEF1A2 and induces oxidative stress, Rac1 activation and JNK1 phosphorylation, triggering a rapid apoptotic program in tumor cells. Since oxidative stress is one of the known sources of endoplasmic reticulum stress, we investigated whether PLD was inducing a bona fide ER stress in HeLa cells and whether this process was essential in the mechanism of action of the compound. Indeed, PLD activated an ER stress-induced unfolded protein response (UPR), including the alternative splicing of XBP1, the proteolytic processing of ATF6 and the phosphorylation of eIF2α and JNK. Interestingly, though PLD induced a strong phosphorylation of eIF2α in all the analyzed cell lines, it did not elicit an increased expression of ATF4 and CHOP, a transcription factor involved in launching UPR-mediated apoptosis. On the contrary, a clear reduction of CHOP protein levels was observed after PLD treatment, most probably due to both the lack of transactivation by ATF4 and its rapid degradation by the ubiquitin/proteasome machinery. Using fibroblasts devoid of each one of the four possible kinases involved in eIF2α phosphorylation, we observed that only PKR was involved in the response to PLD treatment and, accordingly, PKR-/- fibroblasts are shown to be resistant to the apoptogenic activity of the compound. Furthermore, eIF2α phosphorylation itself was shown to be irrelevant for the induction of cell death by PLD. Instead, we reveal that PLD induces an increase in the levels of misfolded proteins while simultaneously inhibiting the autophagic flux. These two effects combined prevent PLD-treated cells from reducing proteotoxic stress and lead to apoptosis. Other anti-myeloma drugs like bortezomib, which target the proteasome, also inhibit the degradation of misfolded proteins through alternate pathways and a synergistic anticancer effect of the PLD plus bortezomib combination has been previously disclosed. The present results extend this synergy to in vivo experiments and provide a mechanistic rationale for this synergy.

Novel non-resorbable polymeric-nanostructured scaffolds for guided bone regeneration.

OBJECTIVE: The aim of this study was to evaluate the bone-regeneration efficiency of novel polymeric nanostructured membranes and the effect of zinc, calcium, titanium, and bone morpho-protein loading on membranes, through an in vivo rabbit model. MATERIAL AND METHODS: Nanostructured membranes of methylmethacrylate were loaded with zinc, calcium, TiO2 nanoparticles, and bone-morphogenetic protein (BMP). These membranes covered the bone defects prepared on the skulls of six rabbits. Animals were sacrificed 6 weeks after surgery. Micro computed tomography was used to evaluate bone architecture through BoneJ pluging and ImageJ script. Three histological processing of samples, including von Kossa silver nitrate, toluidine blue, and fluorescence by the deposition of calcein were utilized. RESULTS: Zn-membranes (Zn-Ms) promoted the highest amount of new bone and higher bone perimeter than both unloaded and Ti-membranes (Ti-Ms). Ca-membranes (Ca-Ms) attained higher osteoid perimeter and bone perimeter than Zn-Ms. The skeleton analysis showed that Zn-Ms produced more branches and junctions at the trabecular bone than BMP-loaded membranes (BMP-Ms). Samples treated with Ti-Ms showed less bone formation and bony bridging processes. Both Zn-Ms and Ca-Ms achieved higher number of osteoblasts than the control group. BMP-Ms and Ca-Ms originated higher number of blood vessels than Ti-Ms and control group. CONCLUSIONS: Zn incorporation in novel nanostructured membranes provided the highest regenerative efficiency for bone healing at the rabbit calvarial defects. CLINICAL RELEVANCE: Zn-Ms promoted osteogenesis and enhanced biological activity, as mineralized and osteoid new bone with multiple interconnected ossified trabeculae appeared in close contact with the membrane.

Lurbinectedin synergizes with immune checkpoint blockade to generate anticancer immunity.

Systemic treatment with the active transcription inhibitor lurbinectedin aims at inducing tumor cell death in hyperproliferative neoplasms. Here we show that cell death induced by lurbinectedin reinstates and enhances systemic anticancer immune responses. Lurbinectedin treatment showed traits of immunogenic cell death, including the exposure of calreticulin, the release of ATP, the exodus of high mobility group box 1 (HMGB1) and type 1 interferon responses in vitro. Lurbinectedin treated cells induced antitumor immunity when injected into immunocompetent animals and treatment of transplanted fibrosarcomas reduced tumor growth in immunocompetent yet not in immunodeficient hosts. Anticancer effects resulting from lurbinectedin treatment were boosted in combination with PD-1 and CTLA-4 double immune checkpoint blockade (ICB), and lurbinectedin combined with double ICB exhibited strong antineoplastic effects. Cured animals exhibited long term immune memory effects that rendered them resistant to rechallenge with syngeneic tumors underlining the potency of combination therapy with lurbinectedin.

Binding of eEF1A2 to the RNA-dependent protein kinase PKR modulates its activity and promotes tumour cell survival.

BACKGROUND: Through several not-fully-characterised moonlighting functions, translation elongation factor eEF1A2 is known to provide a fitness boost to cancer cells. Furthermore, eEF1A2 has been demonstrated to confer neoplastic characteristics on preneoplastic, nontumourigenic precursor cells. We have previously shown that eEF1A2 is the target of plitidepsin, a marine drug currently in development for cancer treatment. Herein, we characterised a new signalling pathway through which eEF1A2 promotes tumour cell survival. METHODS: Previously unknown binding partners of eEF1A2 were identified through co-immunoprecipitation, high-performance liquid chromatography-mass spectrometry and proximity ligation assay. Using plitidepsin to release eEF1A2 from those protein complexes, their effects on cancer cell survival were analysed in vitro. RESULTS: We uncovered that double-stranded RNA-activated protein kinase (PKR) is a novel eEF1A2-interacting partner whose pro-apoptotic effect is hindered by the translation factor, most likely through sequestration and inhibition of its kinase activity. Targeting eEF1A2 with plitidepsin releases PKR from the complex, facilitating its activation and triggering a mitogen-activated protein kinase signalling cascade together with a nuclear factor-κB-dependent activation of the extrinsic apoptotic pathway, which lead to tumour cell death. CONCLUSIONS: Through its binding to PKR, eEF1A2 provides a survival boost to cancer cells, constituting an Achilles heel that can be exploited in anticancer therapy.