Desmoid Tumors: A Comprehensive Review.

Desmoid tumors (DT) are rare, locally aggressive, fibroblastic soft-tissue tumors that are characterized by infiltrative growth and can affect organs and adjacent structures, resulting in substantial clinical burden impacting patients' health-related quality of life. Searches of PubMed, Embase, Cochrane, and key conferences were conducted in November 2021 and updated periodically through March 2023 to identify articles describing the burden of DT. Of 651 publications identified, 96 relevant ones were retained. Diagnosis of DT is challenging because of its morphologic heterogeneity and variable clinical presentation. Patients visit multiple healthcare providers, often facing delays in correct diagnosis. The low incidence of DT (estimated 3-5 cases per million person-years) limits disease awareness. Patients with DT experience a high symptom burden: up to 63% of patients experience chronic pain, which leads to sleep disturbance (73% of cases), irritability (46% of cases), and anxiety/depression (15% of cases). Frequently mentioned symptoms are pain, limited function and mobility, fatigue, muscle weakness, and swelling around the tumor. Overall, quality of life in patients with DT is lower than in healthy controls. There is no treatment approved by the US Food and Drug Administration for DT; however, treatment guidelines reference available options, such as active surveillance, surgery, systemic therapy, and locoregional therapy. Choice of active treatment may depend on tumor location, symptoms, and risk of morbidity. The substantial burden of illness of DT is related to difficulties in timely and accurate diagnosis, high symptom burden (pain and functional limitations), and decreased quality of life. There is a high unmet need for treatments that specifically target DT and improve quality of life.

Disease and economic burden of surgery in desmoid tumors: a review.

INTRODUCTION: Desmoid tumors (DT) are soft-tissue tumors that infiltrate into surrounding structures with ill-defined margins. Although surgery is a potential treatment option, complete excision with negative margins is not often possible, the postsurgery recurrence rate is high, and surgery can result in disfigurement and/or loss of function. AREAS COVERED: We conducted a literature review to assess the burden of surgery in patients with DT, focusing on recurrence rates and functional deficits resulting from surgeries. Since economic data related to DT surgery is lacking, reviews of surgery costs in soft-tissue sarcomas and of general costs of amputations were conducted. Risk factors for DT recurrence after surgery are young age (<30 years), tumor location (extremities), tumor size (>5 cm in greatest diameter), positive resection margins, and history of trauma in the area of the primary tumor. Tumors in the extremities have the highest risk of recurrence (30%-90%). Lower rates of recurrences have been reported when radiotherapy was used after surgery (14%-38%). EXPERT OPINION: Although effective in specific cases, surgery may be associated with poor long-term functional outcomes and higher economic costs. Therefore, it is imperative to find alternative treatments with acceptable efficacy and safety profiles that do not adversely affect functional aspects in patients.

Use of Soft Electrodes in Capacitive Deionization of Solutions.

All efforts to obtain, reuse or purify water are extremely significant for society. Recently, researchers have begun to delve in an idea born decades ago: the desalination of water using highly porous electrodes. It is based on a fundamental aspect of electrical double layers, namely, their huge capacitance. The ions of a solution can be partially removed under the application of an electric field when the solution fills the space between porous electrodes, either bare (CDI, or capacitive deionization), coated with ionic exchange membranes (MCDI) or chemically treated (inverted-CDI or i-CDI). One of the challenges of the last years was to explore new materials and arrangements to improve the efficiency of the system. In this work, we propose a new approach inspired in the electrokinetics of soft particles: a layer of polyelectrolyte (cationic on one electrode, anionic on the opposite one) coats the carbon electrodes, converting them in a sort of "soft" electrode pair. We present a theoretical model and a set of experiments showing how soft electrodes can be successfully employed in capacitive deionization.

Attentional perspectives on context-dependence of information retrieval

Attention has been traditionally understood as an important factor on acquiring new information. A review of the literature suggests that attention, specifically attention to the contexts, also plays a relevant role on information retrieval. It also shows that attention to the contexts is modulated by the ambiguity of the situation, and the informative value contexts have. The virtues and limitations of different attentional theories of learning applied to the explanation of the effects of context change on retrieval of the information are discussed. This analysis uncovers the weaknesses of current research on context processing that should be corrected by future research: The need of independent measures of attention to the contexts, the evaluation of the mechanisms of contextual control, and the possibility of taking an evolutionary perspective on the effects of context change (AU)

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Review of the cost of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) is the second most common medical complication and a cause of excess length of hospital stay. Its incidence and economic burden are expected to increase as the population ages. We reviewed the recent literature to provide updated cost estimates on VTE management. METHODS: Literature search strategies were performed in PubMed, Embase, Cochrane Collaboration, Health Economic Evaluations Database, EconLit, and International Pharmaceutical Abstracts from 2003-2014. Additional studies were identified through searching bibliographies of related publications. RESULTS: Eighteen studies were identified and are summarized in this review; of these, 13 reported data from the USA, four from Europe, and one from Canada. Three main cost estimations were identified: cost per VTE hospitalization or per VTE readmission; cost for VTE management, usually reported annually or during a specific period; and annual all-cause costs in patients with VTE, which included the treatment of complications and comorbidities. Cost estimates per VTE hospitalization were generally similar across the US studies, with a trend toward an increase over time. Cost per pulmonary embolism hospitalization increased from $5,198-$6,928 in 2000 to $8,764 in 2010. Readmission for recurrent VTE was generally more costly than the initial index event admission. Annual health plan payments for services related to VTE also increased from $10,804-$16,644 during the 1998-2004 period to an estimated average of $15,123 for a VTE event from 2008 to 2011. Lower costs for VTE hospitalizations and annualized all-cause costs were estimated in European countries and Canada. CONCLUSION: Costs for VTE treatment are considerable and increasing faster than general inflation for medical care services, with hospitalization costs being the primary cost driver. Readmissions for VTE are generally more costly than the initial VTE admission. Further studies evaluating the economic impact of new treatment options such as the non-vitamin K antagonist oral anticoagulants on VTE treatment are warranted.

Systematic review and network meta-analysis of the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants among patients with nonvalvular atrial fibrillation and CHADS2 score ⩾ 2.

BACKGROUND: The nonvitamin K antagonist oral anticoagulants pivotal clinical trials for stroke prevention in atrial fibrillation have important differences in trial designs and baseline patient characteristics. OBJECTIVE: We sought to evaluate the relative efficacy and safety of edoxaban versus other nonvitamin K antagonist oral anticoagulants in the management of stroke prevention in atrial fibrillation by adjusting for differences in baseline stroke risk and the length of follow-up among the four phase 3 randomized controlled trials. METHODS: We conducted a systematic literature review of randomized controlled trials evaluating the nonvitamin K antagonist oral anticoagulants for stroke prevention in atrial fibrillation and performed a network meta-analysis using data from ENGAGE AF-TIMI 48, RE-LY, ROCKET-AF, and ARISTOTLE, with warfarin as a common comparator. To adjust for between-trial differences in CHADS2 score and length of follow-up, annualized event rates among patients with CHADS2 score ⩾ 2 were analyzed using a mixed Poisson's regression model. RESULTS: Once-daily high-dose edoxaban was associated with significant lower major bleeding episodes compared with once-daily rivaroxaban (risk ratio, 0.76; 95% confidence interval, 0.66-0.89), twice-daily dabigatran 150 mg (risk ratio, 0.78; 95% confidence interval, 0.61-0.84), and twice-daily dabigatran 110 mg (risk ratio, 0.83; 95% confidence interval, 0.71-0.98) and similar bleeding risk compared with twice-daily apixaban (risk ratio, 1.08; 95% confidence interval, 0.91-1.28). Risk of stroke and systemic embolism was similar for the high-dose edoxaban and other nonvitamin K antagonist oral anticoagulant regimens. The low-dose edoxaban regimen was associated with a significant lower risk of major bleeding than other nonvitamin K antagonist oral anticoagulants and a significant higher risk of stroke and systemic embolism compared with apixaban and dabigatran 150 mg. CONCLUSION: Among patients with atrial fibrillation and CHADS2 score ⩾ 2, the high-dose edoxaban regimen may offer similar efficacy to the other nonvitamin K antagonist oral anticoagulants but with a significant major bleeding benefit over rivaroxaban and dabigatran.

Temperature effects on energy production by salinity exchange.

In recent years, the capacitance of the interface between charged electrodes and ionic solutions (the electric double layer) has been investigated as a source of clean energy. Charge is placed on the electrodes either by means of ion-exchange membranes or of an external power source. In the latter method, net energy is produced by simple solution exchange in open circuit, due to the associated decrease in the capacitance of the electric double layer. In this work, we consider the change in capacitance associated with temperature variations: the former decreases when temperature is raised, and, hence, a cycle is possible in which some charge is put on the electrode at a certain potential and returned at a higher one. We demonstrate experimentally that it is thus viable to obtain energy from electric double layers if these are successively contacted with water at different temperatures. In addition, we show theoretically and experimentally that temperature and salinity variations can be conveniently combined to maximize the electrode potential increase. The resulting available energy is also estimated.

Review of challenges in optimizing oral anticoagulation therapy for stroke prevention in atrial fibrillation.

Oral anticoagulant therapy is the mainstay of stroke prevention in patients with atrial fibrillation; it is highly effective at reducing stroke risk, but its use can be limited by increased risk of bleeding. As new oral anticoagulants are available, barriers to optimal use of oral anticoagulation therapy warrant consideration by healthcare professionals and administrators who are seeking to optimize the quality of care for patients with atrial fibrillation. Suboptimal use of oral anticoagulation therapy constitutes an important health problem with significant humanistic and economic consequences. Based on a review of the medical literature published between 2000 and 2011, this article summarizes the literature on the barriers to optimal use of oral anticoagulation therapy, describes the clinical and economic burdens that these barriers add to the burden of atrial fibrillation, and discusses how well the new oral anticoagulants may address some of these issues.

Inhibitors of 20-hydroxyeicosatetraenoic acid (20-HETE) formation attenuate the natriuretic effect of dopamine.

Endogenous renal dopamine is a major physiological regulator of renal ion transport; however its intracellular signaling pathways are not thoroughly understood. The present study examined the role of 20-hydroxyeicosatetraenoic acid (20-HETE), the major cytochrome P450 (CYP4A) metabolite of arachidonic acid formed in the renal cortex, on the natriuretic response to dopamine in Sprague Dawley rats. Infusion of dopamine (1.5µg/kg/min, i.v.) increased urine flow (1.9 fold over basal), sodium excretion (UNaV, 2.7 fold), fractional sodium excretion (FENa, 3.3 fold) and proximal and distal delivery of sodium by 1.5- and 2-fold respectively. Administration of two inhibitors of the synthesis of 20-HETE, 1-aminobenzotriazole (ABT) and N-hydroxy-N'-(-4-butyl-2-methylphenyl)formamidine (HET0016) reduced the response to dopamine by 65%. Induction of the renal expression of CYP4A enzymes with clofibrate did not alter the response to dopamine. The natriuretic response to dopamine was lower in Dahl salt-sensitive rats in comparison to an SS.BN5 consomic strain in which transfer of chromosome 5 from Brown Norway to Dahl salt-sensitive rats upregulates the renal expression of CYP4A protein and the production of 20-HETE. Treatment with HET0016 blocked the renal effects of dopamine in SS.BN5 rats. We also examined the influence of 20-HETE in the natriuretic response to acute volume expansion that is in part mediated via the release of endogenous dopamine. The increase in urine flow, UNaV, FENa and distal FENa following volume expansion was markedly reduced in rats treated with ABT. These results suggest that 20-HETE plays at least a permissive role in the natriuretic response to dopamine.

Context-outcome associations underlie context-switch effects after partial reinforcement in human predictive learning

El valor predictivo que se asigna a claves reforzadas de forma continua se ve afectado por el cambio de contexto cuando éstas se entrenan en un contexto en el que otra clave diferente recibe reforzamiento parcial. Se llevó a cabo un experimento con el objetivo de explorar el mecanismo que subyace a este efecto de cambio de contexto. Se entrenó a participantes humanos en una situación de aprendizaje predictivo en la que una clave recibía reforzamiento parcial mientras que una clave objetivo (C1) recibía reforzamiento continuo en el contexto A y una segunda clave objetivo (U2) no era reforzada en el contexto B. Los participantes del grupo Parcial-Uno no recibieron reforzamiento parcial en B, mientras que los participantes del grupo Parcial-Ambos recibieron el mismo entrenamiento que en el contexto A, pero con claves distintas. Cuando las claves objetivo se probaron en el grupo Parcial-Uno, se observó mayor respuesta en el contexto A que en el contexto B, aunque las diferencias fueron menores ante la clave U2 que ante C1. No se encontraron diferencias entre contextos en el grupo Parcial-Ambos. Estos resultados están en consonancia con la hipótesis de que el cambio de contexto tras el reforzamiento parcial se debe principalmente a la formación de asociaciones contexto-consecuencia, aunque la diferencia entre el tamaño del efecto sobre la clave reforzada y no reforzada sugiere que también podría estar implicado un mecanismo modulador en estos efectos de cambios de contexto(AU)

Predictive value for continuously reinforced cues is affected by context changes when they are trained within a context in which a different cue undergoes partial reinforcement. An experiment was conducted with the goal of exploring the mechanisms underlying this context-switch effect. Human participants were trained in a predictive learning situation in which a cue received partial reinforcement while a target cue received continuous reinforcement in context A (C1) and another target cue was presented unreinforced in context B (U2). Participants in group Partial-One did not receive partial reinforcement in context B, while participants in group Partial-Both received the same training they received in context A, but with different cues. When target cues were tested in group Partial-One, greater responding in context A than in context B was found. Differences were smaller in cue U2 than in cue C1. No differences across contexts were found in group Partial-Both. These results are in agreement with the hypothesis that context-switch effects after partial reinforcement are mainly due to the formation of direct context-outcome associations, though the difference on the effect size on the reinforced and unreinforced cues suggests that a modulator mechanism may be also responsible for these context-switch effects(AU)

Antimitogenic polymer drugs based on AMPS: monomer distribution-bioactivity relationship of water-soluble macromolecules.

A number of polysulfonated molecules have demonstrated their interaction with fibroblast growth factor (FGF), hampering their binding to its receptors (low affinity heparan sulfate proteoglycans (HSPG) and high affinity tyrosine kinase FGF receptors) and inhibiting the intracellular signaling and mitogenic response in cultured endothelial cells. The aim of this work was the synthesis and characterization of new copolymers based on 2-acrylamido-2-methylpropane sulfonic acid (AMPS) with antiproliferative activity for antitumoral applications. N-Vinylpyrrolidone (VP) or butyl acrylate (BA) was copolymerized with the sulfonated monomer to obtain macromolecules with different hydrophilic/hydrophobic balance and distribution of the sulfonated groups within the macromolecules. In vitro cell culture proliferative assays showed that monomer distribution affected the inhibition of the proliferative action of FGF. Reactivity ratios of the systems were determined following the free radical copolymerization by in situ (1)H NMR, and the correlation of the monomer sequence distribution with the bioactivity is discussed.

Assessing the global availability of misoprostol.

OBJECTIVE: To assess the worldwide availability of misoprostol. Documenting the extent of misoprostol use in obstetrics-gynecology is difficult because the drug typically is unregistered for such indications. METHODS: Data for 2002-2007 on annual sales (measured in weight) to hospitals and retail pharmacies, plus manufacturer prices per 200-microg misoprostol, were analyzed for medications containing misoprostol alone or combined with a nonsteroidal anti-inflammatory drug (NSAID); regional and country-specific trends were identified. Consumer prices per pill are documented for all formulations of registered medications. RESULTS: Of the misoprostol sold worldwide, 70% was misoprostol-NSAID-combination drugs; of this, 91% was sold in North America and Western Europe. Asia sold the most misoprostol-only drugs; sales increased dramatically in Bangladesh (by 128%) and India (646%), where various low-price brands are sold. Misoprostol sales decreased in Latin America but increased in the Middle East-North Africa and Sub-Saharan Africa; these regions generally had low amounts sold per population. CONCLUSION: Availability is improving in some low-income regions where misoprostol could significantly reduce maternal deaths due to postpartum hemorrhage and unsafe abortion.

Specific and dynamic detection of palytoxins by in vitro microplate assay with human neuroblastoma cells.

Palytoxin is one of the most complex and biggest molecules known to show extreme acute toxicity. The dinoflagellate Ostreopsis spp., the producer organism of palytoxin, has been shown to be distributed worldwide, thus making palytoxin an emerging toxin. Rat-derived hepatocytes (Clone 9) and BE (2)-M17 human neuroblastoma cells were used to test palytoxin or palytoxin-like compounds by measuring the cell metabolic rate with Alamar Blue. The dose-dependent decrease in viability was specifically inhibited by ouabain in the case of BE (2)-M17 neuroblastoma cells. This is a functional, dynamic and simple test for palytoxins with high sensitivity (as low as 0.2 ng/ml). This method was useful for toxin detection in Ostreopsis extracts and naturally contaminated mussel samples. A comparative study testing toxic mussel extracts by LC (liquid chromatography)-MS/MS (tandem MS), MBA (mouse bioassay), haemolysis neutralization assay and a cytotoxicity test indicated that our method is suitable for the routine determination and monitoring of palytoxins and palytoxin-like compounds.

El envejecimiento como problema / Aging as a problem

Se presenta un trabajo que refleja los criterios principales definitorios de la problemática del envejecimiento, tanto en el orden individual como poblacional, y que a grandes rasgos se definen como marcado incremento de las necesidades médico-sociales a medida que transcurre la vida del individuo y el grupo poblacional de una parte, y de otra la incapacidad que hasta el presente han demostrado de manera general las sociedades en comprender y utilizar las capacidades residuales existentes en las personas de edad, así como de favorecer su incremento. Desde este punto de vista, necesariamente la respuesta debe ser de tipo social, con intervención coordinada inter e intrasectorial siendo además imprescindible la voluntad y decisión política de los gobiernos para desarrollar los programas necesarios conducentes a elevar el bienestar de los ancianos (AU)

El envejecimiento como problema / Aging as a problem

Se presenta un trabajo que refleja los criterios principales definitorios de la problemática del envejecimiento, tanto en el orden individual como poblacional, y que a grandes rasgos se definen como marcado incremento de las necesidades médico-sociales a medida que transcurre la vida del individuo y el grupo poblacional de una parte, y de otra la incapacidad que hasta el presente han demostrado de manera general las sociedades en comprender y utilizar las capacidades residuales existentes en las personas de edad, así como de favorecer su incremento. Desde este punto de vista, necesariamente la respuesta debe ser de tipo social, con intervención coordinada inter e intrasectorial siendo además imprescindible la voluntad y decisión política de los gobiernos para desarrollar los programas necesarios conducentes a elevar el bienestar de los ancianos