Polyphenol Iongel Patches with Antimicrobial, Antioxidant and Anti-Inflammatory Properties.

There is an actual need for developing materials for wound healing applications with anti-inflammatory, antioxidant, or antibacterial properties in order to improve the healing performance. In this work, we report the preparation and characterization of soft and bioactive iongel materials for patches, based on polymeric poly(vinyl alcohol) (PVA) and four ionic liquids containing the cholinium cation and different phenolic acid anions, namely cholinium salicylate ([Ch][Sal]), cholinium gallate ([Ch][Ga]), cholinium vanillate ([Ch][Van]), and cholinium caffeate ([Ch][Caff]). Within the iongels, the phenolic motif in the ionic liquids plays a dual role, acting as a PVA crosslinker and a bioactive compound. The obtained iongels are flexible, elastic, ionic conducting, and thermoreversible materials. Moreover, the iongels demonstrated high biocompatibility, non-hemolytic activity, and non-agglutination in mice blood, which are key-sought material specifications in wound healing applications. All the iongels have shown antibacterial properties, being PVA-[Ch][Sal], the one with higher inhibition halo for Escherichia Coli. The iongels also revealed high values of antioxidant activity due to the presence of the polyphenol, with the PVA-[Ch][Van] iongel having the highest activity. Finally, the iongels show a decrease in NO production in LPS-stimulated macrophages, with the PVA-[Ch][Sal] iongel displaying the best anti-inflammatory activity (>63% at 200 µg/mL).

Ascidian-Inspired Supramolecular Cellulose Nanocomposite Hydrogels with Antibacterial Activity.

The design of ultratough hydrogels has recently emerged as a topic of great interest in the scientific community due to their ability to mimic the features of biological tissues. An outstanding strategy for preparing these materials relies on reversible and dynamic cross-links within the hydrogel matrix. In this work, inspired by the composition of ascidians' tunic, stretchable supramolecular hydrogels combining poly(vinyl alcohol), green tea-derived gallic acid, and rigid tannic acid-coated cellulose nanocrystals (TA@CNC) were designed. The addition of TA@CNC nanofillers in concentrations up to 1.2 wt % significantly impacted the mechanical and viscoelastic properties of the hydrogels due to the promotion of hydrogen bonding with the polymer matrix and polyphenols π-π stacking interactions. These supramolecular associations endow the hydrogels with excellent stretchability and strength (>340%, 540 kPa), low thermoreversible gel-sol transition (60 °C), and remolding ability, while the natural polyphenols provided potential antibacterial properties. These versatile materials can be anticipated to open up new prospects for the rational design of polyphenol-based cellulosic hydrogels for different biomedical applications.

Natural Deep Eutectic Solvents Based on Choline Chloride and Phenolic Compounds as Efficient Bioadhesives and Corrosion Protectors.

Natural deep eutectics solvents (NADES), owing to their high solvation capacity and nontoxicity, are actively being sought for many technological applications. Herein, we report a series of novel NADES based on choline chloride and plant-derived polyphenols. Most of the obtained phenolic NADES have a wide liquid range and high thermal stability above 150 °C. Among them, small-sized polyphenols, like pyrogallol, vanillyl alcohol, or gentisic acid, lead to low-viscosity liquids with ionic conductivities in the order of 10-3 S cm-1 at room temperature. Interestingly, polyphenols possess valuable properties as therapeutic agents, antioxidants, adhesives, or redox-active compounds, among others. Thus, we evaluated the potential of these novel NADES for two applications: bioadhesives and corrosion protection. The mixture of choline chloride-vanillyl alcohol (2:3 mol ratio) and gelatin resulted in a highly adhesive viscoelastic liquid (adhesive stress ≈ 135 kPa), affording shear thinning behavior. Furthermore, choline chloride-tannic acid (20:1) showed an extraordinary ability to coordinate iron ions, reaching excellent corrosion inhibitive efficiencies in mild steel protection.

Gelatin and Tannic Acid Based Iongels for Muscle Activity Recording and Stimulation Electrodes.

Iongels are soft ionic conducting materials, usually composed of polymer networks swollen with ionic liquids (ILs), which are being investigated for applications ranging from energy to bioelectronics. The employment of iongels in bioelectronic devices such as bioelectrodes or body sensors has been limited by the lack of biocompatibility of the ILs and/or polymer matrices. In this work, we present iongels prepared from solely biocompatible materials: (i) a biobased polymer network containing tannic acid as a cross-linker in a gelatin matrix and (ii) three different biocompatible cholinium carboxylate ionic liquids. The resulting iongels are flexible and elastic with Young's modulus between 11.3 and 28.9 kPa. The morphology of the iongels is based on a dual polymer network system formed by both chemical bonding due to the reaction of the gelatin's amines with the polyphenol units and physical interactions between the tannic acid and the gelatin. These biocompatible iongels presented high ionic conductivity values, from 0.003 and up to 0.015 S·cm-1 at room temperature. Furthermore, they showed excellent performance as a conducting gel in electrodes for electromyography and electrocardiogram recording as well as muscle stimulation.

Study of the Evolution of the Plastic Zone and Residual Stress in a Notched T-6061 Aluminum Sample.

Using experimental measurements and numerical computations, this paper focuses on studying the evolution of the plastic zone and how the residual stresses change in a notched T-6061 aluminum sample. Before the crack initiation, digital image measurements were taken to visualize the evolution of the plastic zone. After the sample was fractured, the material microstructure and the residual stresses around the cracked zone were characterized through optical microscopy and X-ray diffractometry. This article describes in detail how the plastic zone evolved around the notch before the crack initiation and shows the close agreement between experimental and numerical data during the load increment. The surface residual stress values around the tip of the notched sample were also measured and computed to give a better understanding of the affected region during the fracture process.

Elastic and Thermoreversible Iongels by Supramolecular PVA/Phenol Interactions.

Iongels have attracted much attention over the years as ion-conducting soft materials for applications in several technologies including stimuli-responsive drug release and flexible (bio)electronics. Nowadays, iongels with additional functionalities such as electronic conductivity, self-healing, thermo-responsiveness, or biocompatibility are actively being searched for high demanding applications. In this work, a simple and rapid synthetic pathway to prepare elastic and thermoreversible iongels is presented. These iongels are prepared by supramolecular crosslinking between polyphenols biomolecules with a hydroxyl-rich biocompatible polymer such as poly(vinyl alcohol) (PVA) in the presence of ionic liquids. Using this strategy, a variety of iongels are obtained by combining different plant-derived polyphenol compounds (PhC) such as gallic acid, pyrogallol, and tannic acid with imidazolium-based ionic liquids, namely 1-ethyl-3-methylimidazolium dicyanamide and 1-ethyl-3-methylimidazolium bromide. A suite of characterization tools is used to study the structural, morphological, mechanical, rheological, and thermal properties of the supramolecular iongels. These iongels can withstand large deformations (40% under compression) with full recovery, revealing reversible transitions from solid to liquid state between 87 and 125 °C. Finally, the polyphenol-based thermoreversible iongels show appropriated properties for their potential application as printable electrolytes for bioelectronics.

Thermally self-assembled biodegradable poly(casein-g-N-isopropylacrylamide) unimers and their application in drug delivery for cancer therapy.

In this work, we report the synthesis of graft copolymers based on casein and N-isopropylacrylamide, which can self-assemble into biodegradable micelles of approximately 80 nm at physiological conditions. The obtained copolymers were degraded by trypsin, an enzyme that is overexpressed in several malignant tumors. Moreover, graft copolymers were able to load doxorubicin (Dox) by ionic interaction with the casein component. In vitro release experiments showed that the in situ assembled micelles can maintain the cargo at plasma conditions but release Dox immediately after their exposition at pH 5.0 and trypsin. Cellular uptake and cytotoxicity assays revealed the efficient delivery to the nucleus and antiproliferative efficacy of Dox in the breast cancer cell line MDA231. Both delivery and therapeutic activity were enhanced in presence of trypsin. Overall, the prepared micelles hold a great potential for their utilization as dual responsive trypsin/pH drug delivery system.

Real-world data from the Portuguese Nivolumab Expanded Access Program (EAP) in previously treated Non Small Cell Lung Cancer (NSCLC).

OBJECTIVE: The main aim of the study was to evaluate the efficacy and safety profile of Nivolumab, an immune-checkpoint-inhibitor antibody, in advanced, previously treated, Non-Small Cell Lung Cancer (NSCLC) patients, in a real world setting. METHODS: We performed a retrospective, multicentre data analysis of patients who were included in the Portuguese Nivolumab Expanded Access Program (EAP). Eligibility criteria included histologically or citologically confirmed NSCLC, stage IIIB and IV, evaluable disease, sufficient organ function and at least one prior line of chemotherapy. The endpoints included Overall Response Rate (ORR), Disease Control Rate (DCR), Progression Free Survival (PFS) and Overall Survival (OS). Safety analysis was performed with the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0, and immune-related Adverse Events (irAEs) were treated according to protocol treatment guidelines. Tumour response was assessed using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Data was analysed using SPSS, version 21.0 (IBM Statistics). RESULTS: From June 2015 to December 2016, a total of 229 patients with advanced NSCLC were enrolled at 30 Portuguese centres. Clinical data were collected up to the end of July 2018. The baseline median age was 64 years (range 37-83) and the majority of patients were males (70.3%) and former/current smokers (69.4%). Patients with non-squamous histology predominated (88.1%), and 67.6% of the patients had received 2 or more prior lines of chemotherapy. Out of 229 patients, data was available for 219 patients (3 patients did not start treatment, while data was unavailable in 7 patients); of the 219 patients, 15.5% were not evaluated for radiological tumour assessment, 1.4% had complete response (CR), 21% partial response (PR), 31% stable disease (SD) and 31.1% progressive disease (PD). Thus, the ORR was 22.4% and DCR was 53.4% in this population. At the time of survival analysis the median PFS was 4.91 months (95% CI, 3.89-6.11) and median OS was 13.21 months (95% CI, 9.89-16.53). The safety profile was in line with clinical trial data. CONCLUSIONS: Efficacy and safety results observed in this retrospective analysis were consistent with observations reported in clinical trials and from other centres.

Photo-curable poly-(ethylene glycol)-fumarate elastomers with controlled structural composition and their evaluation as eluting systems.

Elastomeric poly-ester materials have extraordinary potential for soft tissue engineering applications. In connection, in the last 10 years, cross-linkable oligo-(polyethylene glycol fumarate)s emerged as promising materials for obtaining hydrogels for bone tissue engineering applications. In this work we prepared a new family of photo-curable poly-(ethylene glycol)-fumarate elastomers with controlled structural composition. These novel elastomers were obtained by photo-curing of fumarate pre-polymers based on diethylene glycol and oligo-ethylene glycols (PEGs 200 and 400), under extremely mild experimental conditions using a low power UV source. The synthesis of fumarate pre-polymers, which were obtained by thermal poly-condensation, and the photo-curing process, were both here discussed on the basis of their structural differences and proposed operating mechanisms. Finally, the photo-radical cross-linking reactions were performed in the presence of anti-cancer drugs (doxorubicin and paclitaxel), in order to evaluate the potential application of the elastomers as new eluting systems. Thus, different release profiles were obtained for hydrophilic (doxorubicin) and hydrophobic (paclitaxel) anticancer drugs, and these differences are discussed on the basis of the structure of the elastomers.

Guía retenida y anudada extravascular durante un cateterismo venoso central: reporte de un caso

El cateterismo venoso central (CVC) es un procedimiento común en la práctica médica de especialistas en salas de emergencia, cuidado intensivo y salas de cirugía. Su uso no está libre de complicaciones estas pueden ser de tipo mecánica, infecciosa y trombóticas. Dentro de las complicaciones mecánicas las asociadas con la guía tipo atrapamiento vascular es la más común, pero el anudamiento y el atrapamiento extravascular son muy infrecuentes. Presentamos el caso de una mujer con atrapamiento extravascular de la guía y neumotórax como complicaciones de un CVC subclavio.

Central venous catheterization is a common procedure in the medical practice of specialists of emergency rooms, critical care and surgery rooms. The use of central venous catheters is associated with mechanical infectious and thrombotic complications. Within the mechanical complications, those associated with the guidewire, especially extravascular entrapments are very infrequent. This work presents a case of a female patient with extravascular entrapment of the guidewire and pneumothorax as complications of right subclavian venous catheterization.

[Characteristics of drug interactions in a pediatric intensive care unit]. / Características de las interacciones farmacológicas en una unidad de cuidados intensivos de pediatría.

INTRODUCTION: The aim of this study is to calculate the theoretical frequency of potential drug interactions (PDI) and their characteristics in the therapeutic plan of hospitalized patients in a Pediatric Intensive Care Unit (PICU). PATIENTS AND METHODS: An observational study was conducted which analyzed PICU prescriptions between September and November 2011. The inclusion criteria included to be hospitalized in a PICU, requirements of at least 3 drugs, except those topically applied, either gender, no age limit, no hospital stay required. The Micromedex® 2.0 program was used to detect and classify PDI. RESULTS: Of 223 patients, 100 met inclusion criteria, 610 prescriptions were analyzed and 815 drugs were prescribed. 1,240 PDI were detected in 44 patients; 12 patients received more than 10 drugs each, presenting 1,162 PDI (93.7% of total PDI). 8 patients were hospitalized for more than 10 days, presenting 1,035 PDI (83.5% of total PDI). According to PDI theoretical severity, 37.5% were high, 51.7% moderate, 6.7% low and 4.1% contraindicated. The therapeutic group most involved was antimicrobials (17.6%) and the most frequently involved individual drugs were chloral hydrate (15.9%), midazolam (14.1%) and vecuronium (13.4%). CONCLUSION: PDI were more frequent in patients associated with major polypharmacy and longer hospital stay.

The action of demineralized bovine bone matrix on bone neoformation in rats submitted to experimental alcoholism / Ação da matriz óssea bovina desmineralizada na neoformação óssea em ratos submetidos ao alcoolismo experimental

The objective of this study was to evaluate whether demineralized bovine bone (Gen-ox®) alters bone neoformation in rats submitted to alcoholism. Forty male rats were separated into two groups of 20 rats and distributed as follows: Group E1, which received 25% ethanol and a surgical cavity filled only by a blood clot, and Group E2, which received 25% ethanol and a surgical cavity filled with Gen-ox®. The animals were euthanized at 10, 20, 40 and 60 days after surgery and necropsy was performed. The histomorphological and histometric analyses of the area of connective tissue and bone neoformation showed that the reorganization of the bone marrow and full repair of the surgical cavity in Group E1 occurred more quickly than in Group E2. It was also noted that in the final period the animals in Group E2 showed areas of connective tissue and thick bone trabeculae around the particles of the implant. It can be concluded that the use of Gen-ox® delayed the process of bone repair in alcoholic rats, although it can be used as filling material because it shows osteoconductive activity, as evidenced by bone tissue formation around the graft particles.

O objetivo deste trabalho foi avaliar se a matriz óssea bovina desmineralizada (Gen-ox®) altera a neoformação óssea em ratos submetidos ao alcoolismo. Foram utilizados 40 ratos machos, separados em dois grupos de 20 animais cada, assim distribuídos: Grupo E1, que recebeu etanol a 25% e cavidade cirúrgica preenchida por coágulo sanguíneo, e Grupo E2, que recebeu etanol a 25% e cavidade cirúrgica preenchida por Gen-ox®. Os animais foram eutanasiados aos 10, 20, 40 e 60 dias após a cirurgia. Os estudos histomorfológico e histométrico da quantidade de tecido conjuntivo presente e a quantidade de tecido ósseo neoformado demostraram que a reorganização da medula óssea e a reparação total da cavidade cirúrgica no Grupo E1 ocorreram em menor espaço de tempo do que no Grupo E2. Observou-se também que, no período final do experimento, os animais do Grupo E2 apresentaram áreas de tecido conjuntivo e trabéculas ósseas espessas ao redor das partículas do material implantado. Concluiu-se que a utilização do Gen-ox® retardou o processo de reparação óssea em ratos alcoolizados, muito embora o Gen-ox® possa ser utilizado como material de preenchimento, pois demonstra atividade osteocondutiva, com a formação de tecido ósseo ao redor das partículas do enxerto.

Multiple causes for an ischemic stroke: myxoma, papillary fibroelastomas and patent foramen ovale.

We report a case in which multiple uncommon causes of an ischemic vascular accident coexisted in the same patient. The patient was admitted with signs of acute stroke. Investigation workup revealed a left atrial tumor (myxoma) and a patent foramen ovale. Intraoperatively, transesophageal echocardiography added new information: papillary fibroelastomas were found in the aortic valve. This finding dictated a change in the surgical plan, adding resection of aortic valve masses to the planned excision of the left atrial tumor and patent foramen ovale closure. The uniqueness of this case derives from the coexistence of rare primary cardiac tumors. There are only five cases in literature of myxoma concomitant with fibroelastoma and the occurrence of multiple fibroelastoma is also extremely rare. Moreover this case emphasizes the benefit of the intraoperative use of transesophageal echocardiography to improve the diagnosis and management of cardiac surgical patients.

[Left ventricle free wall rupture - a 10-year experience]. / Rotura de parede livre do ventrículo esquerdo- 10 anos de experiência.

The left ventricle free wall rupture is one of the most serious and lethal complications associated to myocardial infarction.The most common treatment in our days consists in direct closure of the rupture with pericardium or synthetic material, applied with the help of histoacryl glue, without extracorporeal circulation.Between January 2000 and September 2010, 35 consecutive patients underwent operation for left ventricle free wall rupture at our hospital.The mean age was 69,5 years and most of the patients were male ( 65,7 % ). 2,9 days was the mean time for rupture after infarction and the anterior and lateral wall were most frequently involved. 94,7 % of the patients were in shock. Surgery was performed without extracorporeal circulation using a patch of pericardium and/or Dacron Sauvage, with histoacryl glue in 85,7 % of cases.Mean time of ICU stay was 7,9 days, in-hospital global mortality 28,6 %. At 2,5 years follow-up, 86 % of the patients were alive.Despite the high morbidity and mortality associated to surgery, the procedure is now safer, simpler and quick allowing the treatment of a situation that conducted to a most certain death without management.

[Minimally invasive thoracic surgery: a fifteen-years experience]. / Cirurgia torácica minimamente invasiva. Experiêcia de 15 anos.

The evolution of surgical techniques has rendering possible for thoracic surgery to be performed efficiently and safely, with less aggressive approaches. Being less traumatic, minimally invasive surgery allows a faster post-operative recovery, less complications and reduces in patient days and morbidity. The authors consider as minimally invasive approaches the video-assisted thoracic surgery, as well as the minithoractomy and the ministernotomy. The present paper reviews thoracic surgeries performed for the last 15 years in a cardiothoracic surgical unit using a minimally invasive surgical approach.

[Intra-thoracic goiter: analysis of the Department's experience]. / Bócio mergulhante: Análise da casuística do Serviço.

A review of all clinical files with pre-operative diagnosis of intra-thoracic goiter operated in our Department from 2001-2009 was made. We identified 30 patients, of which 66% were females. 63% of the patients were asymptomatic, 46% had clinical or radiological findings of mediastinal structures compression and 2 patients were ventilated prior to surgery. 50% of the patients were operated on through an inferior transverse cervicotomy, the remaining were operated on through partial or complete sternotomy, with cervical approach. 6,6% of patients (n=2) had an intra-operative diagnosis of invasive thymoma, 3,3% (n=1) had a very invasive mediastinal tumor and 3,3% (n=1) had an ectopic thyroid. Average surgical length of time was of 83 minutes. In 10% of patients (n=3) post-operative invasive ventilation was required, one of which for unilateral permanent lesion of the recurrent laryngeal nerve. In the long term follow-up we assessed 18 patients. The median follow up was 53 months. One patient died at the 15th post-operatory day of pneumonia, one expired at the 30th day for anaplasic thyroid carcinoma progression and one died at the 18 month from invasive thymoma progression. One patient currently reveals evidence of local recurrence 3 patients are currently taking levothyroxine and one is taking propiltiouracil. Pathological studies revealed that 66% of cases were multinodular goiter and neoplasia was present in 13% of the patients. Other results were thymic pathology in 13% of cases (n=4), parathyroid cyst in 3,3% (n=1), and ectopic thyroid in 3,3% (n=1(.

[The impact of the "patient - prosthesis mismatch" in patients with aortic valve replacement.]. / Impacto do "patient-prosthesis mismatch" em doentes submetidos a substituição valvular aórtica.

UNLABELLED: Patient-Prosthesis Mismatch (PPM) is still a controversial matter in our days. We have PPM when the orifice area of an implanted aortic prosthesis valve is too small for the body surface area of an individual; this is, when the orifice area indexed to the body surface area is <0.8-0.9 cm2/m2. OBJECTIVE: Assess the impact of Patient-Prosthesis Mismatch in the short term and 2 years follow up in a group of patients submitted to aortic valve replacement. MATERIAL AND METHODS: The authors present a retrospective study involving 343 patients with a mean age of 64,68+/-12,4 years that were submitted to aortic valve replacement between January 2005 and December 2008. Data were collected from patients' files and direct contact with the patients, comparing the groups with and without PPM and correlating them in terms of Euroscore, demographics, type of implanted prosthesis, surgical times, ICU and hospital stay. The data related to short term and long term mortality as well as the NYHA class evolution were also obtained. RESULTS: Using the cut-off related to effective orifice area index 0,9 cm2/m2 we found PPM in 109 patients (31.7%). When comparing the two groups, we found that PPM seems to be related to advanced age (p=0.001), biological prosthesis (p=0.01) and, as expected, with use of valves less than 21 (p<0,05). A statistical significant difference was found for: 1) short-term mortality in patients with PPM (p<0,001), however, there were no differences in 2 years mortality and NYHA class between the groups; 2) aorta's cross clamping and extra corporeal circulation time (p=0.047 and p=0.036, respectively).