Conversion Rate in Pediatric Robotic-Assisted Surgery: Looking for the Culprit.

Introduction: Robotic-assisted surgery (RAS) is increasingly used in adulthood but its application in pediatric population is limited. We report our initial experience in pediatric RAS, focusing on conversions to analyze their causes. Methods: All pediatric patients who underwent RAS between June 2015 and April 2019 were included, analyzing demographics, comorbidities, previous surgery, and intraoperative surgical and anesthetic parameters. A three-arms robotic technique was used in all cases. Additional laparoscopic ports were added, when needed. The surgical team did not change during the program, whereas the anesthesiology team varied. Results: Thirty-nine patients (23 females, 16 males; mean age ± SD = 9.33 ± 4.73 years [range = 1-16]; mean weight ± SD = 35.2 ± 20.0 kg [range = 9-85]) underwent 40 different procedures (18 gastrointestinal, 15 urogynecological, 5 oncological, and 2 miscellaneous). Three procedures (7.5%) were converted to open surgery for inadequate working space (two marked bowel distension and one insufficient hepatic retraction). Converted patients were of significant lower age (mean ± standard error of mean [SEM] = 2.97 ± 1.03 versus 9.83 ± 0.77 years, P = .01) and lower weight (mean ± SEM = 11.83 ± 1.74 versus 35.47 ± 3.16 kg, P = .03). The two groups did not differ statistically for duration of facial mask ventilation before intubation (mean ± SEM = converted 10.67 ± 2.33 versus completed 10.31 ± 0.91 minutes), neuromuscular block dosage (rocuronium; mean ± SEM = converted 0.46 ± 0.06 mg/kg versus completed 0.62 ± 0.03 mg/kg) and in the type of bowel preparation (mechanical and/or pharmacological). Discussion: Conversion rate in initial pediatric RAS program is acceptable. In children, the need for conversion is mainly because of inadequate working space, particularly in smaller children, but it seems not to be influenced by measurable anesthetic factors or different regimen for bowel preparation.

Determination of the polyphenolic fraction of Pistacia vera L. kernel extracts by comprehensive two-dimensional liquid chromatography coupled to mass spectrometry detection.

Pistachio (Pistacia vera L.) belongs to the Anacardiaceae family and it is a small tree species. It is native of the Middle East and Central Asia, but currently, it is cultivated also in California and in some Mediterranean countries, such as Greece and Italy. The most important pistachio producers are Iran, the USA, and Turkey. Besides being a delicious nut, pistachio, due to its wholesome nutritional properties, could be considered as a functional food. According to the results of several studies, pistachios have been proven to have various groups of valuable phytochemicals such as anthocyanins, flavan-3-ols, proanthocyanidins, flavonols, isoflavones, flavanones, stilbenes, and phenolic acids, possessing excellent biological activities. The most common analytical technique employed for their analysis is represented by liquid chromatography coupled to photodiode array and mass spectrometry detection. However, conventional LC can present some limits especially in terms of resolving power. In this contribution, as a powerful alternative, comprehensive two-dimensional liquid chromatography (LC×LC) was applied to the determination of the polyphenolic fraction of pistachio kernels from different geographical origins. A 150-mm micro-bore cyano column (2.7 µm dp) and 50-mm superficially porous C18 silica column (2.7 µm dp) in the first (1D) and second (2D) dimensions were employed, respectively. For boosting orthogonality, a shift 2D gradient was investigated leading to an increase in the overall peak capacity. The newly developed LC×LC method showed satisfactory linearity, sensitivity, precision and accuracy, which was then applied to sample quantitative analysis. A total of 51 different polyphenolic compounds were determined in the four samples investigated and 18 out of them are hereby reported for the first time.

Robot-assisted resection of gastric duplication cysts in a child: a detailed case report.

Gastric duplication cysts (GDCs) represent 4-9% of alimentary tract duplications. Early diagnosis and surgical excision are essential to avoid morbidity or neoplastic degeneration. Roboticassisted excision of GDCs has never been described in childhood. We report an asymptomatic male patient with 2 gastric cystic masses at ultrasonography (US)-study (diameter 25mm and 8mm), increasing in size at follow-up. At 20 months of age, magnetic- resonance-imaging-scan confirmed 2 round gastric masses (44×35mm and 16×12mm, respectively). Two months later, an elective robotic-assisted excision of GDCs was completed without complications. The patient was discharged at day 6 after procedure. Histology confirmed the diagnosis of GDCs. At a 2-year follow- up, US-study did not evidence any issue. In this first reported case of robotic-assisted cystectomy for CGD in childhood, the procedure seems safe, effective, and feasible. This approach improves the movements of the surgical instruments with better 3- D visualization in comparison with the laparoscopic approach.

Electroneutral polymersomes for combined cancer chemotherapy.

Combination cancer chemotherapy provides an important treatment tool, both as an adjuvant and neoadjuvant treatment, this shift in focus from mono to combination therapies has led to increased interest in drug delivery systems (DDS). DDSs, such as polymersomes, are capable of encapsulating large amounts of multiple drugs with both hydrophilic and hydrophobic properties simultaneously, as well as offering a mechanism to combat multi drug resistant cancers and poor patient tolerance of the cytotoxic compounds utilised. In this article, we report the formulation and evaluation of a novel electroneutral polymersome capable of high encapsulation efficacies for multiple drugs (Doxorubicin, 5-Fluorouracil and leucovorin). The in-vivo biodistribution of the polymersome were established and they were found to accumulate largely in tumour tissue. Polymersome encapsulating the three chemotherapeutic drugs were assessed both in-vitro (BxPC-3 cell line) and in-vivo (following intratumoral and intravenous administration) and compared with the same concentration of the three drugs in solution. We report better efficacy and higher maximum tolerated dose for our combination drug loaded polymersomes in all experiments. Furthermore, intratumorally injected combination drug loaded polymersomes exhibited a 62% reduction in tumour volume after 13 days when compared with the free combination solutions. A smaller differential of 13% was observed for when treatment was administered intravenously however, importantly less cardiotoxicity was displayed from the polymersomal DDS. In this study, expression of a number of survival-relevant genes in tumours treated with the free chemotherapy combination was compared with expression of those genes in tumours treated with the polymersomes harbouring those drugs and the significance of findings is discussed. STATEMENT OF SIGNIFICANCE: The shift in focus from mono to combination chemotherapies has led to an increased interest in the role of drug delivery systems (DDS). Liposomes, although commercialized for mono therapy, have lower loading capacities and stability than their polymeric counterpart, polymersomes. Polymersomes are growing in prevalence as their advantageous properties are better understood and exploited. Here we present a novel polymersome for the encapsulation of three anticancer compounds. This is the first time this particular polymersome has been used to encapsulate these three compounds with both an in-vitro and in-vivo evaluation carried out. This work will be of interest to those in the field of combination therapy, drug delivery, drug toxicity, multidrug resistance, liposomes, DDS and polymersomes.

Confined photo-release of nitric oxide with simultaneous two-photon fluorescence tracking in a cellular system.

Nitric oxide (NO) is a key signaling molecule in biological systems. New tools are required to therapeutically modulate NO levels with confined precision. This study explores the photoactivatable properties of an NO releasing compound (CPA), based on cupferron O-alkylated with an anthracene derivative. Upon light stimulation, CPA uncages two species: cupferron, which liberates NO, and an anthrylmethyl carbocation, which evolves into a fluorescent reporter. Proof-of-principle is demonstrated using one- and two-photon excitation (1PE and 2PE) in a cellular system (A431 cells). It was found that 1PE induces cell toxicity, while 2PE does not. Since 1PE using UV light is more likely to generate cellular photodamage, the cell toxicity observed using 1PE is most likely a combinatory effect of NO release and other UV-induced damage, which should be subject to further investigation. On the other hand, absence of phototoxicity using 2PE suggests that NO alone is not cytotoxic. This leads to the conclusion that the concept of 2PE photorelease of NO from CPA enable opportunities for biological studies of NO signaling with confined precision of NO release with minimal cytotoxicity.

The integration of triggered drug delivery with real time quantification using FRET; creating a super 'smart' drug delivery system.

The ability to control drug release at a specific physiological target enables the possibility of an enhanced therapeutic effect with reduced off-target toxic side effects. The discipline of controlled drug release has grown to include most areas of medicine with examples in the literature of targeted drug delivery to the majority of organs within the human body. In addition, a variety of external stimuli used to meditate the drug release process have also been investigated. Nonetheless, the concurrent real time monitoring of drug release has not been widely studied. In this manuscript, we present a novel micellar drug delivery system that is not only capable of releasing its cargo when stimulated by light but also provides a real time analysis of the amount of cargo remaining. Controlled drug release from the delivery system was mediated by physicochemical changes of a spiropyran-merocyanine photochromic dyad, while drug quantification was enabled using a Förster Resonance Energy Transfer (FRET) relationship between the photochrome and a co-encapsulated BODIPY fluorophore. The percentage of drug released from the delivery system was significantly greater (24%) when exposed to light irradiation compared to an analogous control maintained in the dark (5%). Furthermore, the fluorescence read-out capability also enabled the drug-release process to be followed in living cells with a significantly reduced fluorescence emission observed for those cells incubated with the delivery system and exposed to light irradiation compared to control cells maintained in the dark. Combined, these results highlight the utility of this approach to theranostic drug delivery with the potential of light-triggered released together with a fluorescence read-out to enable quantification of the drug release process.

A water-soluble pillar[5]arene as a new carrier for an old drug.

The remarkable affinity of deca-carboxylatopillar[5]arene WP5 towards the aminoglycoside antibiotic, amikacin, in aqueous media is reported; in vitro studies on Gram-positive bacteria (Staphylococcus aureus) show that drug entrapment inside WP5 also takes place in the presence of the microrganisms, thus pointing to WP5 as an appealing carrier for amikacin targeted delivery.

Pluronic® P123/F127 mixed micelles delivering sorafenib and its combination with verteporfin in cancer cells.

Here, we developed Pluronic® P123/F127 (poloxamer) mixed micelles for the intravenous delivery of the anticancer drug sorafenib (SRB) or its combination with verteporfin (VP), a photosensitizer for photodynamic therapy that should complement well the cytotoxicity profile of the chemotherapeutic. SRB loading inside the core of micelles was governed by the drug:poloxamer weight ratio, while in the case of the SRB-VP combination, a mutual interference between the two drugs occurred and only specific ratios could ensure maximum loading efficiency. Coentrapment of SRB did not alter the photophysical properties of VP, confirming that SRB did not participate in any bimolecular process with the photosensitizer. Fluorescence resonance energy-transfer measurement of micelles in serum protein-containing cell-culture medium demonstrated the excellent stability of the system in physiologically relevant conditions. These results were in line with the results of the release study showing a release rate of both drugs in the presence of proteins slower than in phosphate buffer. SRB release was sustained, while VP remained substantially entrapped in the micelle core. Cytotoxicity studies in MDA-MB231 cells revealed that at 24 hours, SRB-loaded micelles were more active than free SRB only at very low SRB concentrations, while at 24+24 hours a prolonged cytotoxic effect of SRB-loaded micelles was observed, very likely mediated by the block in the S phase of the cell cycle. The combination of SRB with VP under light exposure was less cytotoxic than both the free combination and VP-loaded micelles + SRB-loaded micelles combination. This behavior was clearly explainable in terms of micelle uptake and intracellular localization. Besides the clear advantage of delivering SRB in poloxamer micelles, our results provide a clear example that each photochemotherapeutic combination needs detailed investigations on their particular interaction, and no generalization on enhanced cytotoxic effects should be derived a priori.

Cholesteryl to improve the cellular uptake of polymersomes within HeLa cells.

The need to develop a greater understanding of drug delivery systems has arisen through the development of alternative biological based therapeutics. Drug delivery systems need to adapt and respond to this increasing demand for cellular transportation of highly charged species. Polymersomal drug delivery systems have displayed great potential and versatility for such a task. In this manuscript we present the synthesis, characterisation and biological evaluation of six amphiphilic random co polymers with varying amounts of cholesteryl (0-39%wt) before the subsequent formation into polymersomes. The polymersomes were then analysed for size, zeta potential, encapsulation efficiency, release kinetics and cellular uptake. Results confirmed that the polymersome containing 12%wt cholesteryl polymer displayed a ten-fold increase in cellular uptake of Fitc-CM-dextran when compared to un-encapsulated drug, crossing the cellular membrane via endocytosis. The size of these vehicles ranged between 100 and 500nm, zeta potential was shown to be neutral at -0.82mV ±0.2 with encapsulation efficiencies in the region of 60%. The ease of adaptability and preparation of such systems renders them a viable alternative to liposomal drug delivery systems.

Phototherapeutic Release of Nitric Oxide with Engineered Nanoconstructs.

The multiple role nitric oxide (NO) plays in a number of physiological and pathophysiological processes has, over the last few years, stimulated a massive interest in the development of new strategies and methods for generating NO in a controlled way, with the exciting prospect of tackling important diseases. Photochemical precursors of NO are particularly suited to this end because light triggering permits an exquisite control of location and timing of NO delivery. Integration of NO photodonors within the structure of appropriate materials represents a key step in the fabrication of functional devices for phototherapeutic applications. It also offers the advantage of concentrating a large number of chromophores in a restricted area with the result of significantly increasing the NO reservoir and the light harvesting properties. We present here an overview of the most significant advances made in the last 5 years in the fabrication of engineered nanoconstructs able to delivery NO under the exclusive control of light inputs, highlighting the logical design and their potential applications in battling cancer and bacterial infections.

Light-Tunable Generation of Singlet Oxygen and Nitric Oxide with a Bichromophoric Molecular Hybrid: a Bimodal Approach to Killing Cancer Cells.

The design, synthesis, photochemical properties, and biological evaluation of a novel photoactivatable bichromophoric conjugate are reported. The compound 1, [4-(4,4-difluoro-2,6-diiodo-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacen-8-yl)-N-(3-((4-nitro-3-(trifluoromethyl)phenyl)amino)propyl)butanamide] combines a 2,6-diiodo-1,3,5,7-tetramethyl BODIPY derivative as singlet oxygen ((1) O2 ) photosensitizer and 4-nitro-3-(trifluoromethyl)aniline (NOPD) as nitric oxide (NO) photodonor, joined by an alkyl spacer. These two chromogenic units absorb in distinct regions of the visible spectrum, and their individual photochemical properties are conserved in the molecular conjugate. Irradiation of the bichromophoric conjugate with green light afforded (1) O2 in high quantum yields, whereas (1) O2 production was negligible with the use of blue light; under this latter condition, NO was released. Photogeneration of NO and cytotoxic (1) O2 can therefore be regulated by appropriately tuning the excitation light wavelength and intensity. Tested on melanoma cancer cells, this resulted in amplified photomortality relative to that of a structurally correlated model compound 2 [4-(4,4-difluoro-2,6-diiodo-1,3,5,7-tetramethyl-4-bora-3a,4a-diaza-s-indacen-8-yl)-N-(3-(p-tolylamino)propyl)butanamide] deprived of the NO-release capacity. The cellular uptake of 1, evaluated by confocal fluorescence microscopy, showed that the product is localized in the cytoplasm.

Photo-antimicrobial polymeric films releasing nitric oxide with fluorescence reporting under visible light.

A novel photoresponsive molecular hybrid has been embedded in poly(lactic-co-glycolic acid) (PLGA) to give an antibacterial polymeric film generating nitric oxide (NO) under visible light, with concomitant fluorescence reporting of NO release. The molecular hybrid integrates a nitroaniline NO photodonor and a coumarin latent fluorophore in the same molecular skeleton and results in quite homogeneous distribution in the polymer matrix where it preserves well the photobehavior exhibited in solution. The doped PLGA film shows an excellent optical transparency and can be excited by visible light leading to the production of NO and the parallel fluorescence revival of the coumarin fluorophore, which acts as an optical NO reporter. Photogenerated NO diffuses out of the polymer film, can be transferred to a biological milieu and induces remarkable antibacterial activity against Escherichia coli.

Graphene oxide nanohybrid that photoreleases nitric oxide.

We report herein a photoresponsive nanoplatform that delivers nitric oxide (NO) on demand, achieved by the covalent functionalization of graphene oxide (GO) with an amino-terminated nitric oxide (NO) photodonor (NOP1). The resulting GO-NOP1 hybrid nanomaterial is dispersible in water, is very stable in the dark and has been thoroughly characterized by SEM, TEM, AFM, XRD, FTIR and UV-Vis absorption spectroscopy. Photolysis experiments demonstrate that the photodecomposition of the NO photoreleaser integrated into the GO scaffold occurs with an efficiency similar to that observed for a free model compound, ruling out any significant quenching effect (i.e. photoinduced energy/electron transfer) and accounting for the excellent preservation of its photochemical properties upon grafting. A combination of direct amperometric detection and indirect measurements based on a fluorometric assay prove that the remote-controlled release of NO from the GO-NOP1 nanoplatform is exclusively regulated by visible light stimuli.

Transmisión oral de la enfermedad de chagas: con especial referencia a la patología de los casos del año 2009 / Oral transmission of chagas disease due to oral: with special reference to the pathology of the cases from the year 2009

La transmisión oral de la enfermedad de Chagas habitual en el ciclo selvático es una forma rará en el ser humano. En este último, se debe a la contaminación de las heces con Trypanosoma cruzi (Tcruzi) en los alimentos o a la manipulación infectada de los mismos. Más raramente a la ingesta de carne de reservorios infectados. En esta comunicación, se ponen en el tapete, los trabajos experimentales y naturales del investigador Díaz-Ungría quien demostró el importante papel que juega la mosca doméstica en la contaminación de los alimentos con las heces infectadas de los vectores. Igualmente, se destaca la importancia del perro como reservorio doméstico, todos los cuales podrían ser factores determinantes en la causa de los brotes agudos presentados en los dos últimos años en nuestro país. Se exponen las características de la miocarditis aguda chagásica como la expresión más constante de la forma aguda de la enfermedad por transmisión oral. Se destacan las medidas de prevención efectuadas por las autoridades sanitarias en estas circunstancias

Oral transmission of Chagas disease is common in the forest'cycle and is a rare form in humans. In the human is due to contamination of the stool with T.cruzi in food or infected by their manipulation. More rarely due to reservoirs infected T.cruzi meat intake. In this communication we described the natural and experimental works of the Díaz-Ungría researcher who demonstrated the important role played bi the house fly in the contamination of food with vectors infected faeces. It also highlights the importance of the dog as domestic reservoir, all of which could be determining factors in the cause of acute outbreaks in the past two years in our country. The features of acute Chagasic'myocarditis are exposed as the constant expression of the acute form of the disease by oral transmission. The prevention measures carried out by the health authorities in these circunstances are high lighted

Use of real time three-dimensional transesophageal echocardiography in intracardiac catheter based interventions.

BACKGROUND: Real-time three-dimensional (RT3D) echocardiography is a recently developed technique that is being increasingly used in echocardiography laboratories. Over the past several years, improvements in transducer technologies have allowed development of a full matrix-array transducer that allows acquisition of pyramidal-shaped data sets. These data sets can be processed online and offline to allow accurate evaluation of cardiac structures, volumes, and mass. More recently, a transesophageal transducer with RT3D capabilities has been developed. This allows acquisition of high-quality RT3D images on transesophageal echocardiography (TEE). Percutaneous catheter-based procedures have gained growing acceptance in the cardiac procedural armamentarium. Advances in technology and technical skills allow increasingly complex procedures to be performed using a catheter-based approach, thus obviating the need for open-heart surgery. METHODS: The authors used RT3D TEE to guide 72 catheter-based cardiac interventions. The procedures included the occlusion of atrial septal defects or patent foramen ovales (n=25), percutaneous mitral valve repair (e-valve clipping; n=3), mitral balloon valvuloplasty for mitral stenosis (n=10), left atrial appendage obliteration (n=11), left atrial or pulmonary vein ablation for atrial fibrillation (n=5), percutaneous closures of prosthetic valve dehiscence (n=10), percutaneous aortic valve replacement (n=6), and percutaneous closures of ventricular septal defects (n=2). In this review, the authors describe their experience with this technique, the added value over multiplanar two-dimensional TEE, and the pitfalls that were encountered. RESULTS: The main advantages found for the use RT3D TEE during catheter-based interventions were (1) the ability to visualize the entire lengths of intracardiac catheters, including the tips of all catheters and the balloons or devices they carry, along with a clear depiction of their positions in relation to other cardiac structures, and (2) the ability to ability to demonstrate certain structures in an "en face" view, which is not offered by any other currently available real-time imaging technique, enabling appreciation of the exact nature of the lesion that is undergoing intervention. CONCLUSION: RT3D TEE is a powerful new imaging tool that may become the technique of choice and the standard of care for guidance of selected percutaneous catheter-based procedures.

Percutaneous closure of a post-myocardial infarction ventricular septal defect guided by real-time three-dimensional echocardiography.

We present an adult patient who had an acute myocardial infarction complicated by a ventricular septal defect and had it repaired percutaneously. Real-time three-dimensional echocardiography (RT3D) before and during the closure procedure were performed. RT3D provided anatomical and functional information of the defect as well as real-time guidance during the procedure. This case highlights the utility of three-dimensional echocardiography in guiding transcatheter procedures.

Refractory hypotension and edema caused by right atrial compression in a woman with polycystic kidney disease.

We present the case of a 60-year-old woman with a history of autosomal dominant polycystic kidney disease and long-standing hypertension who developed persistent hypotension. While in the hospital for the treatment of bacteriemia, the patient had low systolic blood pressures (90 to 100 mm Hg), which was thought to be the consequence of infection. After the infection was adequately controlled and the blood pressure did not improve, an echocardiogram was done to further elucidate her hypotension. It was nondiagnostic and revealed an ejection fraction of 70% with left ventricular hypertrophy. Shortly after discharge, she developed significant lower extremity edema and her blood pressure remained low. Due to the low blood pressure it was not possible to mobilize the fluid with her dialysis treatments. A repeat transthoracic echocardiogram at that time revealed that the right atrium was partially compressed throughout the cardiac cycle by polycystic hepatic tissue. This tissue invaginated up through the right hemidiaphragm. A partial liver resection was considered for the patient. Instead, right nephrectomy was performed and the blood pressure improved.