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OBJECTIVE: To compare the short-term effects on acid base, electrolyte status and urine output of a single fluid bolus of saline to that of the balanced solution Plasmalyte® in critically ill patients. METHODS: Prospective, randomized, controlled trial. Adult patients (≥ 18 years) admitted to the ICU receiving a fluid bolus were randomized to receive 1 L of saline (NaCl 0.9%, Baxter) or a balanced fluid [Plasmalyte® (Baxter)]. Blood samples and urine output were collected just before (T0), just after (T1), 2 h after (T2) (only for urinary output) and three hours after termination of the fluid bolus (T4). The effect of fluid boluses on serum chloride, apparent strong ion difference, base excess, urinary output and blood pressure or vasopressor need were analyzed. MAIN RESULTS: Patients who received a 1 L saline fluid bolus had a significant increase in serum chloride (1.60; 95% CI 1.10 to 2.10; P < 0.001) and short-term decrease in apparent strong ion difference (- 1.85; 95% CI - 2.71 to - 0.99; P < 0.001) and base excess (- 0.90; 95% CI - 1.31 to - 0.50; P < 0.001). We observed a 17% increase in patients developing hyperchloremia in the saline group (0.17; 95% CI 0.05 to 0.29; P = 0.005). No significant difference in urinary output, blood pressure or vasopressor need was observed in either group. CONCLUSION: Even a single, small bolus of saline, administered to critically ill patients, causes a significant increase in chloride concentration and a decrease in apparent strong ion difference and base excess, and an increase in the number of patients developing hyperchloremia. No difference in effect on urinary output, blood pressure or vasopressor need was observed between the two groups. EUDRACT NUMBER: 2014-001005-41; date of registration: 28/10/2014. LOCAL EC APPROVAL: EC project number 2014/038.
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There is a crucial need for low-cost energy storage technology based on abundant sodium ions to realize sustainable development with renewable energy resources. Poly(vinylidene fluoride) (PVDF) is applied as a binder in sodium-ion batteries (SIBs). Nevertheless, PVDF is also known to suffer from a larger irreversible capacity, especially when PVDF is used as the binder of negative electrode materials. In this research, a poly(acrylonitrile)-grafted poly(vinyl alcohol) copolymer (PVA-g-PAN) is tested as a binder with Ti-based layered oxides as potential negative electrode materials for SIBs. The chemical stability tests of PVDF and PVA-g-PAN contacted with metallic sodium have been conducted, which reveals that PVDF experiences a defluorination process, while PVA-g-PAN demonstrates excellent chemical stability. Composite electrodes with PVA-g-PAN demonstrate superior electrochemical performances when compared with the PVDF binder, allowing improvement for initial CE, higher rate capability, and long cyclability over 1500 cycles. Detailed characterization of electrodes via soft X-ray photoelectron spectroscopy and field emission scanning electron microscopy demonstrates that the PVA-g-PAN branched structure allows a more uniform distribution of acetylene black with higher coatability, unlocking enhanced rate performances and efficient passivation of Ti-based oxides without the excessive electrolyte decomposition. These findings open a new way to design practical and durable sodium-ion batteries with a high-power density.
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All-solid-state-batteries (ASSBs) necessitate the preparation of a solid electrolyte and an electrode couple with individually dense and compact structures with superior interfacial contact to minimize overall cell resistance. A conventional preparation method of solid polymer electrolyte (SPE) with polyethylene-oxide (PEO) generally consists in employing uni-axial hot press (HP) to densify SPE. However, while uni-axial press with moderate pressure effectively densifies PEO with Li salts, excessive pressure also unavoidably results in perpendicular elongation and deformation for polymer matrix. In this research, to overcome this limitation for the uni-axial press technique, a cold isostatic press (CIP) is applied to the fabrication of ASSB with PEO and LiFePO4 . CIP effectively and uniformly applies pressure as high as 500â MPa without deformation. Characterizations confirm that CIP treated SPE has enhanced mechanical puncture strength, increasing from 499.3±22.6 to 539.3±22.6â g, and ionic conductivity, increasing from 1.04×10-4 to 1.91×10-4 â S cm-1 at 50 °C. ASSB treated by CIP demonstrates remarkably enhanced rate capability and cyclability compared with the cell processed by HP, which is further evidenced by improvement of the apparent Li ion diffusion constant based on Sand equation analysis. The improvement enabled by CIP treatment originates from the superior interface uniformity between electrodes and SPE and from the densification of the LiFePO4 and SPE composite electrode.
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Ge-rich Ge2Sb2Te5(GGST) is considered as one of the best candidates for industrial phase change memory production. GGST memory cells are generally embedded with Si or Ti nitride layers to prevent oxidation, as it leads to an undesired decrease of the GGST crystallization temperature. Furthermore, GGST films are usually doped with elements such as N, C, O, or Bi, aiming to delay GGST crystallization during the fabrication process as well as during memory cell operation. In this work, ultrahigh vacuum thermal desorption spectroscopy (TDS) was performed during isochronal annealing of a N-doped GGST film covered by a 10 nm-thick TiNxlayer. Desorption is observed before GGST crystallization, but the comparison between TDS andin situx-ray diffraction measurements shows that the main desorption peak, observed between 653 K and 703 K, occurs after GGST full crystallization. The most prominent desorbing species are Ar, N2, H2, and H. These results show that the TiNxpolycrystalline layer cannot prevent N atoms from leaving the GGST layer during annealing, suggesting a progressive change of the N-doped GGST chemical composition during thermal annealing and crystallization.
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This Delphi exercise aimed to gather consensus surrounding risk factors, diagnosis, and management of chyle leaks after esophagectomy and to develop recommendations for clinical practice. Background: Chyle leaks following esophagectomy for malignancy are uncommon. Although they are associated with increased morbidity and mortality, diagnosis and management of these patients remain controversial and a challenge globally. Methods: This was a modified Delphi exercise was delivered to clinicians across the oesophagogastric anastomosis collaborative. A 5-staged iterative process was used to gather consensus on clinical practice, including a scoping systematic review (stage 1), 2 rounds of anonymous electronic voting (stages 2 and 3), data-based analysis (stage 4), and guideline and consensus development (stage 5). Stratified analyses were performed by surgeon specialty and surgeon volume. Results: In stage 1, the steering committee proposed areas of uncertainty across 5 domains: risk factors, intraoperative techniques, and postoperative management (ie, diagnosis, severity, and treatment). In stages 2 and 3, 275 and 250 respondents respectively participated in online voting. Consensus was achieved on intraoperative thoracic duct ligation, postoperative diagnosis by milky chest drain output and biochemical testing with triglycerides and chylomicrons, assessing severity with volume of chest drain over 24 hours and a step-up approach in the management of chyle leaks. Stratified analyses demonstrated consistent results. In stage 4, data from the Oesophagogastric Anastomosis Audit demonstrated that chyle leaks occurred in 5.4% (122/2247). Increasing chyle leak grades were associated with higher rates of pulmonary complications, return to theater, prolonged length of stay, and 90-day mortality. In stage 5, 41 surgeons developed a set of recommendations in the intraoperative techniques, diagnosis, and management of chyle leaks. Conclusions: Several areas of consensus were reached surrounding diagnosis and management of chyle leaks following esophagectomy for malignancy. Guidance in clinical practice through adaptation of recommendations from this consensus may help in the prevention of, timely diagnosis, and management of chyle leaks.
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Utilisation of CO2 as a chemical reagent is challenging, due to the molecule's inherent chemical stability. However, CO2 reacts promptly at high temperature (â¼1000 °C) with alkaline-earth oxides to form carbonates and such reactions are used towards capture and re-utilisation. In this work, this concept is extended and CO2 is utilised as a reagent to modify the crystal structure of mixed-metal inorganic solids. Modification of the crystal structure is a "tool" used by materials scientists to tailor the physical property of solids. CO2 gas was reacted with several isostructural mixed-metal oxides Sr2 CuO3 , Sr1.8 Ba0.2 CuO3 and Ba2 PdO3 . These oxides are carefully selected to show anion vacancies in their crystal structure, to act as host sites for CO2 molecules, leading to the formation of carbonate anions, (CO3 )2- . The corresponding oxide carbonates were formed successfully and the favourable formation of SrCO3 as secondary phase was minimised via an innovative, yet simple synthetic procedure involving alternating of CO2 and air. We also derived a simple model to predict the kinetics of the reactions for the cuprates, using first-principles density functional theory and assimilating the reaction to a gas-surface process.
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Cerebral ischemia is a pathology involving a cascade of cellular mechanisms, leading to the deregulation of proteostasis, including macroautophagy/autophagy, and finally to neuronal death. If it is now accepted that cerebral ischemia induces autophagy, the effect of thrombolysis/energy recovery on proteostasis remains unknown. Here, we investigated the effect of thrombolysis by PLAT/tPA (plasminogen activator, tissue) on autophagy and neuronal death. In two in vitro models of hypoxia reperfusion and an in vivo model of thromboembolic stroke with thrombolysis by PLAT/tPA, we found that ischemia enhances neuronal deleterious autophagy. Interestingly, PLAT/tPA decreases autophagy to mediate neuroprotection by modulating the PI3K-AKT-MTOR pathways both in vitro and in vivo. We identified IGF1R (insulin-like growth factor I receptor; a tyrosine kinase receptor) as the effective receptor and showed in vitro, in vivo and in human stroke patients and that PLAT/tPA is able to degrade IGFBP3 (insulin-like growth factor binding protein 3) to increase IGF1 (insulin-like growth factor 1) bioavailability and thus IGF1R activation.Abbreviations: AKT/protein kinase B: thymoma viral proto-oncogene 1; EGFR: epidermal growth factor receptor; Hx: hypoxia; IGF1: insulin-like growth factor 1; IGF1R: insulin-like growth factor I receptor; IGFBP3: insulin-like growth factor binding protein 3; Ka: Kainate; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAPK/ERK: mitogen-activated protein kinase; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; OGD: oxygen and glucose deprivation; OGDreox: oxygen and glucose deprivation + reoxygentation; PepA: pepstatin A1; PI3K: phosphoinositide 3-kinase; PLAT/tPA: plasminogen activator, tissue; PPP: picropodophyllin; SCH77: SCH772984; ULK1: unc-51 like kinase 1; Wort: wortmannin.
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Isquemia Encefálica , Accidente Cerebrovascular , Autofagia , Isquemia Encefálica/tratamiento farmacológico , Glucosa/farmacología , Humanos , Hipoxia , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/farmacología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Oxígeno/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Accidente Cerebrovascular/tratamiento farmacológico , Serina-Treonina Quinasas TOR/metabolismo , Terapia Trombolítica , Activador de Tejido Plasminógeno/metabolismo , Activador de Tejido Plasminógeno/farmacologíaRESUMEN
Tissue-type plasminogen activator (tPA) plays roles in the development and the plasticity of the nervous system. Here, we demonstrate in neurons, that by opposition to the single chain form (sc-tPA), the two-chains form of tPA (tc-tPA) activates the MET receptor, leading to the recruitment of N-Methyl-d-Aspartate receptors (NMDARs) and to the endocytosis and proteasome-dependent degradation of NMDARs containing the GluN2B subunit. Accordingly, tc-tPA down-regulated GluN2B-NMDAR-driven signalling, a process prevented by blockers of HGFR/MET and mimicked by its agonists, leading to a modulation of neuronal death. Thus, our present study unmasks a new mechanism of action of tPA, with its two-chains form mediating a crosstalk between MET and the GluN2B subunit of NMDARs to control neuronal survival.
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Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , Activador de Tejido Plasminógeno/metabolismo , Animales , Muerte Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Feto , Ratones , Cultivo Primario de Células , Isoformas de Proteínas , Proteínas Proto-Oncogénicas c-met/fisiología , Receptor Cross-Talk/fisiología , Receptores de N-Metil-D-Aspartato/metabolismo , Transducción de Señal , Activador de Tejido Plasminógeno/fisiologíaRESUMEN
BACKGROUND: After lung transplantation (LT), gastroparesis is frequent, occurring in 25-63% of cases and leading to pulmonary infections. In refractory disease, classical management has demonstrated limited efficacy. Gastric peroral endoscopic myotomy (G-POEM) is a recently developed safe and effective procedure that has been performed here on five patients with severe post-LT gastroparesis. METHODS: In all patients, the diagnosis was confirmed by disturbed gastric emptying scintigraphy and GCSI calculation showing severe disease. Upper gastrointestinal endoscopies confirmed the absence of organic lesions. All patients were informed about the procedure and signed informed consent forms. The procedure consisted of performing an endoscopic pyloromyotomy under general anesthesia. RESULTS: The patients were between 35 and 64 years of age. Four had chronic disease, starting approximately 1 year following LT, and one had acute, severe gastroparesis requiring intubation in the intensive care unit. All patients underwent G-POEM after failure of medical treatment, without any complications. Three of the patients with chronic disease improved; they resumed a normal diet and gained weight. The patient with acute disease was discharged within a few days following the procedure and resumed oral intake. CONCLUSION: G-POEM is promising for managing post-LT refractory gastroparesis and should be further evaluated.
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Acalasia del Esófago , Gastroparesia , Trasplante de Pulmón , Piloromiotomia , Esfínter Esofágico Inferior , Gastroparesia/etiología , Gastroparesia/cirugía , Humanos , Trasplante de Pulmón/efectos adversos , Resultado del TratamientoRESUMEN
Carbon materials with controlled pore sizes at the nanometer level have been obtained by template methods, chemical vapor desorption, and extraction of metals from carbides. However, to produce porous carbons with controlled pore sizes at the Ångstrom-level, syntheses that are simple, versatile, and reproducible are desired. Here, we report a synthetic method to prepare porous carbon materials with pore sizes that can be precisely controlled at the Ångstrom-level. Heating first induces thermal polymerization of selected three-dimensional aromatic molecules as the carbon sources, further heating results in extremely high carbonization yields (>86%). The porous carbon obtained from a tetrabiphenylmethane structure has a larger pore size (4.40 Å) than those from a spirobifluorene (4.07 Å) or a tetraphenylmethane precursor (4.05 Å). The porous carbon obtained from tetraphenylmethane is applied as an anode material for sodium-ion battery.
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This study examines the synthesis and electrochemical performance of three-dimensional graphene for Li-ion batteries and Na-ion batteries. The in situ formation of iron hydroxide nanoparticles (Fe(OH)x NPs) of various weights on the surface of graphene oxide, followed by thermal treatment at elevated temperature and washing using hydrochloric acid, furnished 3D graphene. The characterization studies confirmed the prevention of graphene layer stacking by over 90% compared with thermal treatment without Fe(OH)x. The electrochemical performance of the 3D graphene was evaluated as a counter electrode for lithium metal and sodium metal in a half-cell configuration. This material showed good performances with a charging capacity of 507 mA h g-1 at 372 mA g-1 in Li-ion batteries and 252 mA h g-1 at 100 mA g-1 in Na-ion batteries, which is 1.4 and 1.9 times higher, respectively, than the graphene prepared without Fe(OH)x templates.
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Cerebral ischemia is a complex pathology involving a cascade of cellular mechanisms, which deregulate proteostasis and lead to neuronal death. Proteostasis refers to the equilibrium between protein synthesis, folding, transport, and protein degradation. Within the brain proteostasis plays key roles in learning and memory by controlling protein synthesis and degradation. Two important pathways are implicated in the regulation of proteostasis: the unfolded protein response (UPR) and macroautophagy (called hereafter autophagy). Both are necessary for cell survival, however, their over-activation in duration or intensity can lead to cell death. Moreover, UPR and autophagy can activate and potentiate each other to worsen the issue of cerebral ischemia. A better understanding of autophagy and ER stress will allow the development of therapeutic strategies for stroke, both at the acute phase and during recovery. This review summarizes the latest therapeutic advances implicating ER stress or autophagy in cerebral ischemia. We argue that the processes governing proteostasis should be considered together in stroke, rather than focusing either on ER stress or autophagy in isolation.
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Although recent technical advances in thrombectomy have revolutionised acute stroke treatment, prevalence of disability and death related to stroke remain high. Therefore, plasminogen activators-eukaryotic, bacterial, or engineered forms that can promote fibrinolysis by converting plasminogen into active plasmin and facilitate clot breakdown-are still commonly used in the acute treatment of ischaemic stroke. Hence, plasminogen activators have become a crucial area for clinical investigation for their ability to recanalise occluded arteries in ischaemic stroke and to accelerate haematoma clearance in haemorrhagic stroke. However, inconsistent results, insufficient evidence of efficacy, or reports of side-effects in trial settings might reduce the use of plasminogen activators in clinical practice. Additionally, the mechanism of action for plasminogen activators could extend beyond the vessel lumen and involve plasminogen-independent processes, which would suggest that plasminogen activators have also non-fibrinolytic roles. Understanding the complex mechanisms of action of plasminogen activators can guide future directions for therapeutic interventions in patients with stroke.
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Fibrinólisis/efectos de los fármacos , Accidente Cerebrovascular/terapia , Activador de Tejido Plasminógeno/farmacología , Activador de Tejido Plasminógeno/uso terapéutico , Animales , HumanosRESUMEN
Coagulopathy during lung transplantation leads to 2 major problems: first, control of diffuse bleeding becomes challenging and second, massive lung edema can cause significant volume expansion. To control these potentially lethal complications, we used a combined technique of pleural packing and delayed chest wall closure with negative pressure wound therapy. We retrospectively reviewed 100 bilateral lung transplants performed in our institute over the past 30 months and identified 7 cases of coagulopathy. Five of the 7 were weaned from pleural packing and ECMO, and had a secondary chest wall closure. The combination of pleural packing and delayed wall closure is a effective management option in cases of coagulopathy and lung edema.
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Trasplante de Pulmón/efectos adversos , Terapia de Presión Negativa para Heridas/métodos , Pleura/cirugía , Complicaciones Posoperatorias/terapia , Edema Pulmonar/terapia , Terapia Recuperativa/métodos , Técnicas de Sutura , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Edema Pulmonar/etiología , Reoperación , Estudios RetrospectivosRESUMEN
PURPOSE: Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown. METHODS: In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis. RESULTS: Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0-1.00) and 85.9% (75.4-92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20-2.92) or receiving a written TLD (HR 2.32, CI 1.11-4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former. CONCLUSION: Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life.
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Unidades de Cuidados Intensivos , Cultura Organizacional , Calidad de Vida , Procedimientos Innecesarios , Factores de Edad , Europa (Continente) , Humanos , Unidades de Cuidados Intensivos/ética , Estudios ProspectivosRESUMEN
Radiotherapy for head and neck cancers commonly causes damage to salivary gland tissue, resulting in xerostomia (dry mouth) and numerous adverse medical and quality-of-life issues. Amifostine is the only Food and Drug Administration-approved radioprotective drug used clinically to prevent xerostomia. However, systemic administration of amifostine is limited by severe side effects, including rapid decrease in blood pressure (hypotension), nausea, and a narrow therapeutic window. In this study, we demonstrate that retroductal delivery of amifostine and its active metabolite, WR-1065, to murine submandibular glands prior to a single radiation dose of 15 Gy maintained gland function and significantly increased acinar cell survival. Furthermore, in vivo stimulated saliva secretion was maintained in retrograde-treated groups at levels significantly higher than irradiated-only and systemically treated groups. In contrast to intravenous injections, retroductal delivery of WR-1065 or amifostine significantly attenuated hypotension. We conclude that localized delivery to salivary glands markedly improves radioprotection at the cellular level, as well as mitigates the adverse side effects associated with systemic administration. These results support the further development of a localized delivery system that would be compatible with the fractionated dose regimen used clinically.
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Amifostina/administración & dosificación , Protectores contra Radiación/administración & dosificación , Glándulas Salivales/efectos de la radiación , Células Acinares/efectos de los fármacos , Células Acinares/efectos de la radiación , Amifostina/uso terapéutico , Animales , Femenino , Técnica del Anticuerpo Fluorescente , Inyecciones , Mercaptoetilaminas/administración & dosificación , Mercaptoetilaminas/uso terapéutico , Ratones , Ratones Endogámicos C57BL , Traumatismos Experimentales por Radiación/patología , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/uso terapéutico , Glándulas Salivales/efectos de los fármacos , Glándulas Salivales/patología , Glándula Submandibular/efectos de los fármacos , Glándula Submandibular/efectos de la radiaciónRESUMEN
A systematic approach to the synthesis of organocatalyzed oligo(d,l-lactide) demonstrates that choice of initiator, catalytic ratio, and reaction time yields well-controlled oligomers. Ring-opening polymerization of d,l-lactide with the initiator α-methyl propargyl alcohol, a secondary alcohol, used in excess of 4-dimethylaminopyridine catalyst mitigates cyclicization, transesterification, and catalyst-initiated side reactions. This approach enables the design of uniform lactide oligomers for controlled release applications, such as delivery systems for drugs, prodrugs, and molecular sensors.
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Boerhaave syndrome (BS) is a spontaneous esophageal perforation which carries high mortality. Surgical treatment is well established, but the development of interventional endoscopy has proposed new therapies. We expose our experience in a Gastrointestinal and Endoscopy Unit. With a retrospective, observational, open-label, single center, consecutive case series. All patients diagnosed with BS who were managed in our center were included. Treated conservatively, endoscopically or surgically, according to their clinical condition and lesion presentation. Fourteen patients were included. Ten were treated with primary surgery. One conservatively. In total, 7/14 patients required an endoscopic treatment. All required metallic stents deployment, 3 cases over-the-scope-clips concomitantly and one case a novel technique an internal drain. 6/7 cases endoscopically treated achieved complete esophageal healing. In conclusion, endoscopy is an useful tool at all stages BS management: difficult diagnosis, primary treatment in selected patients and as salvage when surgery fails. With mortality rates and outcomes comparables to surgery.
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Humanos , Diagnóstico , Endoscopía , Perforación del Esófago , Procedimientos Quirúrgicos Mínimamente Invasivos , Mortalidad , Estudios Retrospectivos , Stents , Instrumentos QuirúrgicosRESUMEN
The unfolded protein response (UPR) is an endoplasmic reticulum (ER) -related stress conserved pathway that aims to protect cells from being overwhelmed. However, when prolonged, UPR activation converts to a death signal, which relies on its PERK-eIF2α branch. Overactivation of the UPR has been implicated in many neurological diseases, including cerebral ischaemia. Here, by using an in vivo thromboembolic model of stroke on transgenic ER stress-reporter mice and neuronal in vitro models of ischaemia, we demonstrate that ischaemic stress leads to the deleterious activation of the PERK branch of the UPR. Moreover, we show that the serine protease tissue-type plasminogen activator (tPA) can bind to cell surface Grp78 (78 kD glucose-regulated protein), leading to a decrease of the PERK pathway activation, thus a decrease of the deleterious factor CHOP, and finally promotes neuroprotection. Altogether, this work highlights a new role and a therapeutic potential of the chaperone protein Grp78 as a membrane receptor of tPA capable to prevent from ER stress overactivation.