Complete Blood Count Alterations Prior to the Diagnosis of Colorectal Cancer May Help in the Detection of Synchronous Liver Metastases.

Background and Aims: Colorectal cancer (CRC) represents 10% of all cancers worldwide with the highest incidence in developed countries; its incidence is also increasing in middle- and low-income countries. Population screening programs facilitate early diagnosis of the disease. When the diagnosis is carried out in advanced stages, approximately 80% of patients with liver metastases (LM) are considered unresectable at the time of diagnosis. In our study, variations in blood counts prior to CRC diagnosis were analyzed to assess whether they could be useful in identifying smaller, more manageable metastases at earlier stages for more effective treatment. Methods: A study was carried out using complete blood counts (CBCs) from CRC patients, obtained from primary health centers and the La Ribera University Hospital within La Ribera Health Department, Valencian Community, Spain, between July 2012 and September 2020. Data from CRC patients who presented synchronous liver metastasis (CRLM) were compared with those with CRC without LM at diagnosis (CRC patients). Results: Our analysis shows that at least 15 months before CRC diagnosis, a progressive alteration was observed in CBC parameters in both groups. A higher incidence of anemia (p < 0.001) was observed among CRLM patients in the three months prior to CRC diagnosis than in CRC patients showing no LM. Conclusions: A statistically significant deterioration of CBC was observed in patients with advanced-stage CRC and synchronous or early LM (CRLM) in the three months prior to diagnosis. The primary goal of incorporating CBC variations into predictive models is to identify individuals who are at a greater risk of developing metastatic colon cancer, leading to early diagnosis. Our research improves these models by highlighting a more pronounced and rapid decline in hemoglobin levels among CRLM patients. Identification of metastases at an earlier stage when they are smaller, more manageable, and more amenable to treatment may be a valuable tool to prevent their further progression.

Biodistribution of progesterone in the eye after topical ocular administration via drops or inserts.

Progesterone (PG) has been shown to have a slowing effect on photoreceptor cell death in mouse models of retinitis pigmentosa when administered orally. The aim of this study was to investigate whether ophthalmically administered progesterone was able to reach neuroretina and thus, the distribution through ocular tissues of different PG formulations was studied. The effect of different initial PG concentration was also investigated. Different formulations with PG in their composition (drops, a corneal/scleral-insert and scleral-inserts) were prepared and assayed. Using whole porcine eyes, the different formulations were topically administered to the ocular surface. Frozen eyes were dissected, the PG in each tissue was extracted in acetonitrile and the amount of PG quantified by UHPLC-MS/MS. Our results show that after topical administration, PG diffuses from the ocular surface and distributes throughout all tissues of the eye. Lower levels of PG were found in sclera, choroid and neuroretina when PG was applied as drops compared to inserts. Our results also show that an increase in the initial PG concentrations applied, resulted in a statistically significant increase in the amounts of PG in aqueous humour, sclera, choroid and neuroretina.

Topical Ocular Administration of Progesterone Decreases Photoreceptor Cell Death in Retinal Degeneration Slow (rds) Mice.

Retinitis pigmentosa (RP) is an inherited eye disorder which triggers a cascade of retinal disorders leading to photoreceptor cell death and for which there is currently no effective treatment. The purpose of this research was to study whether ocular administration of a solution of progesterone (PG) in ß-cyclodextrins (CD) could delay photoreceptor cell death and counteract the gliosis process in an animal model of RP (rds mice). The possible effect of PG reaching the contralateral eye through the circulatory system was also evaluated. Finally, this research discusses and evaluates the diffusion of the drug from possible topical formulations for ocular administration of PG. A group of rds mice received one drop of a solution of PG in CD every 12 h for 10 days to the left eye, while the right eye was left untreated. Another group of rds mice (control) received the drug vehicle (PBS) on the left eye and, again, the right eye was left untreated. Once the treatment was finished on postnatal day 21, the animals were euthanized and histological immunofluorescence studies (TUNEL, GFAP, and DAPI staining) were carried out. Our results showed that the administration of a solution of PG in CD (CD-PG) as drops significantly decreased cell death and inflammation in the retina of the PG-treated eyes of rds mice. No effect was seen in the contralateral eye from PG that may have entered systemic circulation. In conclusion, CD-PG applied topically as drops to the eye decreases photoreceptor cell death in the early stages of RP, delaying vision loss and decreasing gliosis.

Potential Neuroprotective Role of Sugammadex: A Clinical Study on Cognitive Function Assessment in an Enhanced Recovery After Cardiac Surgery Approach and an Experimental Study.

Background: Postoperative cognitive dysfunction affects the quality of recovery, particularly affecting the elderly, and poses a burden on the health system. We hypothesize that the use of sugammadex (SG) could optimize the quality of postoperative cognitive function and overall recovery through a neuroprotective effect. Methods: A pilot observational study on patients undergoing cardiac surgery with enhanced recovery after cardiac surgery (ERACS) approach, was designed to compare SG-treated (n = 14) vs. neostigmine (NG)-treated (n = 7) patients. The Postoperative Quality Recovery Scale (PQRS) was used at different times to evaluate cognitive function and overall recovery of the patients. An online survey among anesthesiologists on SG use was also performed. Additionally, an animal model study was designed to explore the effects of SG on the hippocampus. Results: Sugammadex (SG) was associated with favorable postoperative recovery in cognitive domains particularly 30 days after surgery in patients undergoing aortic valve replacement by cardiopulmonary bypass and the ERACS approach; however, it failed to demonstrate a short-term decrease in length of intensive care unit (ICU) and hospital stay. The survey information indicated a positive appreciation of SG recovery properties. SG reverts postoperative memory deficit and induces the expression of anti-inflammatory microglial markers. Conclusion: The results show a postoperative cognitive improvement by SG treatment in patients undergoing aortic valve replacement procedure by the ERACS approach. Additionally, experimental data from an animal model of mild surgery confirm the cognitive effect of SG and suggest a potential effect over glia cells as an underlying mechanism.

3D Printing of Temporary Prostheses for Controlled-Release of Drugs: Design, Physical Characterization and Preliminary Studies.

In recent years, the use of 3D printing technologies in orthopedic surgery has markedly increased, as they offer the possibility of printing personalized prostheses. The work presented in this article is a preliminary study of a research project which aims to manufacture customized spacers containing antibiotics for use in joint replacement surgery. The objective of this work was to design and print different 3D constructs to evaluate the use of different materials, their properties after the process of 3D printing, such as resistance, and the release kinetics of drugs from the constructs. Different designs and different materials were analyzed to obtain a 3D construct with suitable properties. Our design takes advantage of the micropores created between the layers of the 3D printed filaments to release the contained drug. Using polylactic acid (PLA) we were able to print cylindrical structures with interconnected micropores and a hollow chamber capable of releasing methylene blue, which was selected as a model drug. The final PLA 3D construct was printed with a 10% infill. The physical and technological characteristics, morphological changes at body temperature and interaction with water were considered to be acceptable. The PLA 3D printed constructs were found to have sufficient strength to withstand a force of 500 kg. The results obtained allow to continue research in this project, with the aim of manufacturing prostheses containing a reservoir of antibiotics or other drugs in their interior for their subsequent controlled release.

Development, characterization, and ex vivo evaluation of an insert for the ocular administration of progesterone.

Progesterone (PG) affords neuroprotection in degenerative diseases associated to oxidative stress, such as cataracts, age-related macular degeneration, glaucoma, diabetic retinopathy and retinitis pigmentosa. The aim of this project was to develop ocular inserts for delivery of PG to the eye. Different inserts with PG in its composition were formulated and the insert with the best characteristics (59% polyvinyl alcohol, 39% polyvinylpyrrolidone K30 and 2% propylene glycol) was selected for ex vivo studies. Physical characteristics and drug release patterns of the insert were analysed. In vitro diffusion studies revealed a controlled diffusion of progesterone. Ex vivo experiments demonstrated similar trans-corneal and trans-scleral PG diffusion (corneal apparent permeability coefficient 6.46 ± 0.38 × 10-7 cm/s and scleral apparent permeability coefficient 5.87 ± 1.18 × 10-7 cm/s; mean ± SD; n = 5). However, the amount of PG accumulated in scleras was statistically higher than in corneas (30.07 ± 9.09 µg/cm2 and 15.56 ± 4.36 µg/cm2 respectively). The PG-loaded inserts (55.6 µg/cm2) were thin, translucent, showed no irritancy (HET-CAM test) and were elastic and robust, all suitable properties for its potential use in the treatment of several ocular diseases.

HPLC-UV analytical validation of a method for quantification of progesterone in ex vivo trans-corneal and trans-scleral diffusion studies.

Progesterone (PG) diminishes free radical damage and thus can afford protection against oxidative stress affecting the retina. The therapeutic use of PG is limited because it is a highly hydrophobic steroid hormone with very low solubility in water. This is the main drawback for the therapeutic application of PG at ocular level. The aims of this study were: (i) to analyze if PG causes ocular irritation (ii) to validate a HPLC method to determine PG in ex vivo studies and (iii) to evaluate PG permeation through cornea and sclera. A high performance liquid chromatographic method was developed and validated to detect PG incorporated to ß-cyclodextrin using a Waters Sunfire C18 (150 × 4.6 mm) reverse-phase column packed with 5 µm silica particles using a mobile phase consisted of a mixture of acetonitrile (ACN) and pure water 80:20 (v/v), pH 7.4. The limit of detection and the limit of quantification for 50 µL injection of PG were found to be 0.42 and 1.26 µg/mL, respectively. The calibration curve showed excellent linearity over the concentration range (0.5 µg/mL to 100 µg/mL). As proof of concept, ex-vivo experiments to investigate PG permeation through cornea and sclera with vertical diffusion cells were carried out to quantify PG diffusion. Ex vivo experiments demonstrate its applicability to investigate permeation levels of PG from 6.57 ±â€¯0.37 µg/cm2 at cornea and 8.13 ±â€¯0.85 µg/cm2 sclera. In addition, at the end of diffusion studies the amount of PG retained in each tissue was also quantified, and it was 40.87 ±â€¯9.84 µg/cm2 (mean ±â€¯SD; n = 6) in cornea and 56.11 ±â€¯16.67 µg/cm2 (mean ±â€¯SD; n = 6) in sclera.

Ex-Vivo Trans-Corneal and Trans-Scleral Diffusion Studies with Ocular Formulations of Glutathione as an Antioxidant Treatment for Ocular Diseases.

Exposure to sunlight and contact with atmospheric oxygen makes the eye particularly susceptible to oxidative stress, which can potentially produce cellular damage. In physiological conditions, there are several antioxidant defense mechanisms within the eye. Glutathione (GSH) is the most important antioxidant in the eye; GSH deficit has been linked to several ocular pathologies. The aim of this study was to explore the potential for newly developed formulations allowing controlled delivery of antioxidants such as GSH and vitamin C (Vit C) directly to the eye. We have investigated the stability of antioxidants in aqueous solution and assessed ex-vivo the diffusion of GSH through two ocular membranes, namely cornea and sclera, either in solution or included in a semisolid insert. We have also carried out the hen's egg-chlorioallantoic membrane test (HET-CAM) to evaluate the ocular irritancy of the different antioxidant solutions. Our results showed that GSH is stable for up to 30 days at 4 °C in darkness and it is not an irritant to the eye. The diffusion studies revealed that the manufactured formulation, a semisolid insert containing GSH, could deliver this tripeptide directly to the eye in a sustained manner.

Micelles of Progesterone for Topical Eye Administration: Interspecies and Intertissues Differences in Ex Vivo Ocular Permeability.

Progesterone (PG) may provide protection to the retina during retinitis pigmentosa, but its topical ocular supply is hampered by PG poor aqueous solubility and low ocular bioavailability. The development of efficient topical ocular forms must face up to two relevant challenges: Protective barriers of the eyes and lack of validated ex vivo tests to predict drug permeability. The aims of this study were: (i) To design micelles using Pluronic F68 and Soluplus copolymers to overcome PG solubility and permeability; and (ii) to compare drug diffusion through the cornea and sclera of three animal species (rabbit, porcine, and bovine) to investigate interspecies differences. Micelles of Pluronic F68 (3-4 nm) and Soluplus (52-59 nm) increased PG solubility by one and two orders of magnitude, respectively and exhibited nearly a 100% encapsulation efficiency. Soluplus systems showed in situ gelling capability in contrast to the low viscosity Pluronic F68 micelles. The formulations successfully passed the hen's egg-chorioallantoic membrane test (HET-CAM) test. PG penetration through rabbit cornea and sclera was faster than through porcine or bovine cornea, although the differences were also formulation-dependent. Porcine tissues showed intermediate permeability between rabbit and bovine. Soluplus micelles allowed greater PG accumulation in cornea and sclera whereas Pluronic F68 promoted a faster penetration of lower PG doses.

El arte como herramienta docente en medicina / Art as a resource for teaching medical students

El presente artículo forma parte de un proyecto que pretende formar a estudiantes en la observación de la enfermedad utilizando para ello obras de arte. Los objetivos son desarrollar el interés científico de los participantes, promover y desarrollar la afición por el arte en estudiantes con formación básicamente científica. La peste negra, aunque fue una de las mayores catástrofes del mundo pre-modernista, produjo un obligado avance en la medicina. En este contexto histórico, a través de la representación de san Roque se vislumbra el impacto social de la pandemia gracias a la herencia artística del gótico, del renacimiento y del barroco (siglos XIV a xvii). MATERIAL Y MÉTODOS: Se han analizado algunas obras pictóricas sobre san Roque y, aprovechando la visión artística e histórica de su figura, se ha recopilado información de la labor y relación de san Roque con la peste bubónica. RESULTADOS Y DISCUSIÓN: A través de contenidos artísticos de la figura san Roque se observa una correlación bastante fidedigna entre la clínica representada en los cuadros de san Roque y los signos descritos en la medicina interna e infecciosa actual. Los signos y síntomas comunes de la peste aparecen fielmente representados en las obras analizadas dado que algunos de los pintores que dedicaron trabajos a su figura convivieron con la enfermedad e incluso la padecieron

INTRODUCTION: This article forms part of a project intended to teach students about observation through artwork. The objectives were to promote and develop art appreciation in science students, as well to continue developing their scientific interest. Although bubonic plague was one of the greatest catastrophes in the pre-modern world, it was also partly responsible for major advances in medicine. In this historic context, and using the figure of Saint Roch, a Catholic saint and confessor especially invoked against the plague, the social impact of the pandemic is assessed using the artistic heritage of gothic, renaissance and baroque periods (fourteen to seventeenth centuries). MATERIAL AND METHODS: Some paintings of Saint Roch have been analysed by looking at the historical and artistic viewpoints in order to gather information about his work and the relationship of the Saint with the bubonic plague. RESULTS AND DISCUSSION: Through the artistic representations of Saint Roch, and after a bibliographic review, a good correlation can be established between the clinical signs shown in the paintings and those described by in current internal medicine and knowledge of infections. There is ample evidence showing the fidelity of the representations regarding the common signs and symptoms of Black Death, particularly as some of the painters who painted the Saint lived at the time of the epidemics and even suffered the disease themselves

Factors associated with self-medication in Spain: a cross-sectional study in different age groups.

OBJECTIVE: The identification of factors which may influence a patient's decision to self-medicate. METHODS: Descriptive, cross-sectional study of the adult population (at least 16 years old), using data from the 2009 European Health Interview Survey in Spain, which included 22 188 subjects. Logistic regression models enabled us to estimate the effect of each analysed variable on self-medication. KEY FINDINGS: In total, 14 863 (67%) individuals reported using medication (prescribed and non-prescribed) and 3274 (22.0%) of them self-medicated. Using logistic regression and stratifying by age, four different models have been constructed. Our results include different variables in each of the models to explain self-medication, but the one that appears on all four models is education level. Age is the other important factor which influences self-medication. Self-medication is strongly associated with factors related to socio-demographic, such as sex, educational level or age, as well as several health factors such as long-standing illness or physical activity. CONCLUSIONS: When our data are compared to those from previous Spanish surveys carried out in 2003 and 2006, we can conclude that self-medication is increasing in Spain.

A cross-sectional evaluation of the prevalence and detection of predictors of polypharmacy amongst adult in Spain.

OBJECTIVE: To investigate the association between polypharmacy and sociodemographic factors as well as health status, determinants of health and healthcare use, illness and use of prescribed medicines amongst adults in Spain. METHODS: Data from the 2009 European Health Interview Survey in Spain which included 22 188 subjects were used. Polypharmacy was defined as the use of five or more prescribed medicines. The association between polypharmacy and several variables was assessed by means of bivariate analysis and logistic regression analysis (adjusted by age and gender). KEY FINDINGS: Amongst study participants, 15.8% were on prescribed polypharmacy (19.3%, women; 10.3%, men (P < 0.001)). A number of sociodemographic factors (e.g. age, gender, educational level), health status factors (e.g. limitation in daily activities, self-perception of health, presence of chronic disease) and other health-related factors (e.g. smoking, alcohol drinking, physical activity) have been studied and have been found to play a role in polypharmacy. Logistic regression analysis provided three variables which together with age could be used to predict polypharmacy. CONCLUSION: In Spain, approximately 16% of people who take medicines are on polypharmacy and this is more frequent in women and amongst older adults. From our study, we can conclude that the variables which can predict a higher likelihood of polypharmacy are, together with age, prescribed antidepressants, and prescribed medicines for back/neck pain and joint pain. This may provide a tool for health professionals to readily assess polypharmacy appropriateness in polymedicated patients.

Ex vivo rabbit cornea diffusion studies with a soluble insert of moxifloxacin.

The objective of this research was to develop and evaluate an ocular insert for the controlled drug delivery of moxifloxacin which could perhaps be used in the treatment of corneal keratitis or even bacterial endophthalmitis. We have evaluated the ex vivo ocular diffusion of moxifloxacin through rabbit cornea, both fresh and preserved under different conditions. Histological studies were also carried out. Subsequently, drug matrix inserts were prepared using bioadhesive polymers. The inserts were evaluated for their physicochemical parameters. Ophthalmic ex vivo permeation of moxifloxacin was carried out with the most promising insert. The formulate insert was thin and provided higher ocular diffusion than commercial formulations. Ocular diffusion studies revealed significant differences between fresh and frozen corneas. Histological examinations also showed differences in the thickness of stroma between fresh and frozen corneas. The ophthalmic insert we have developed allows a larger quantity of moxifloxacin to permeate through the cornea than existing commercial formulations of the drug. Ocular delivery of moxifloxacin with this insert could be a new approach for the treatment of eye diseases.