Inteligencia Artificial en Medicina y Salud: revisión y clasificación de las aplicaciones actuales y del futuro cercano y su impacto ético y social

This paper provides an overview of the current and near-future applications of Artificial Intelligence (AI) in Medicine and Health Care and presents a classification according to their ethical and societal aspects, potential benefits and pitfalls, and issues that can be considered controversial and are not deeply discussed in the literature. This work is based on an analysis of the state of the art of research and technology, including existing software, personal monitoring devices, genetic tests and editing tools, personalized digital models, online platforms, augmented reality devices, and surgical and companion robotics. Motivated by our review, we present and describe the notion of “extended personalized medicine”, we then review existing applications of AI in medicine and healthcare and explore the public perception of medical AI systems, and how they show, simultaneously, extraordinary opportunities and drawbacks that even question fundamental medical concepts. Many of these topics coincide with urgent priorities recently defined by the World Health Organization for the coming decade. In addition, we study the transformations of the roles of doctors and patients in an age of ubiquitous information, identify the risk of a division of Medicine into “fake-based”, “patient-generated”, and “scientifically tailored”, and draw the attention of some aspects that need further thorough analysis and public debate

Polarimetric imaging for the detection of synthetic models of SARS-CoV-2: A proof of concept

Objective: To conduct a proof-of-concept study of the detection of two synthetic models of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) using polarimetric imaging. Approach: Two SARS-CoV-2 models were prepared as engineered lentiviruses pseudotyped with the G protein of the vesicular stomatitis virus, and with the characteristic Spike protein of SARS-CoV-2. Samples were prepared in two biofluids (saline solution and artificial saliva), in four concentrations, and deposited as 5-µL droplets on a supporting plate. The angles of maximal degree of linear polarization (DLP) of light diffusely scattered from dry residues were determined using Mueller polarimetry from87 samples at 405 nm and 514 nm. A polarimetric camera was used for imaging several samples under 380–420 nm illumination at angles similar to those of maximal DLP. Per-pixel image analysis included quantification and combination of polarization feature descriptors in 475 samples. Main results: The angles (from sample surface) of maximal DLP were 3° for 405 nm and 6° for 514 nm. Similar viral particles that differed only in the characteristic spike protein of the SARS-CoV-2, their corresponding negative controls, fluids, and the sample holder were discerned at 10-degree and 15-degree configurations. Significance: Polarimetric imaging in the visible spectrum may help improve fast, non-contact detection and identification of viral particles, and/or other microbes such as tuberculosis, in multiple dry fluid samples simultaneously, particularly when combined with other imaging modalities. Further analysis including realistic concentrations of real SARS-CoV-2 viral particles in relevant human fluids is required. Polarimetric imaging under visible light may contribute to a fast, cost-effective screening of SARS-CoV-2 and other pathogens when combined with other imaging modalities.12 página

Hyperspectral image processing for the identification and quantification of lentiviral particles in fluid samples

Optical spectroscopic techniques have been commonly used to detect the presence of biofilm-forming pathogens (bacteria and fungi) in the agro-food industry. Recently, near-infrared (NIR) spectroscopy revealed that it is also possible to detect the presence of viruses in animal and vegetal tissues. Here we report a platform based on visible and NIR (VNIR) hyperspectral imaging for non-contact, reagent free detection and quantification of laboratory-engineered viral particles in fluid samples (liquid droplets and dry residue) using both partial least square-discriminant analysis and artificial feed-forward neural networks. The detection was successfully achieved in preparations of phosphate buffered solution and artificial saliva, with an equivalent pixel volume of 4 nL and lowest concentration of 800 TU.mu L-1. This method constitutes an innovative approach that could be potentially used at point of care for rapid mass screening of viral infectious diseases and monitoring of the SARS-CoV- 2 pandemic.This research was funded by grants number COV20-00080 and COV20-00173 of the 2020 Emergency Call for Research Projects about the SARS-CoV-2 virus and the COVID-19 disease of the Institute of Health 'Carlos III', Spanish Ministry of Science and Innovation, and by grant number EQC2019-006240-P of the 2019 Call for Acquisition of Scientific Equipment, FEDER Program, Spanish Ministry of Science and Innovation. This work has been supported by the European Commission through the JRC HUMAINT project. ABR was supported by grant number RTI2018-094465-J funded by the Spanish National Agency of Research. The authors would like to gratefully acknowledge the assistance of the members of the EOD-CBRN Group of the Spanish National Police, whose identities cannot be disclosed, and who are represented here by JMNG. Authors thank continuous support from their institutions

Clinical Outcomes after Surgical Resection Combined with Brachytherapy for Uveal Melanomas

Currently, brachytherapy is the most commonly used therapeutic approach for uveal melanomas. Surgical resection by means of endoresection or exoresection is an alternative approach. The present report recounts our experience over 15 years in the treatment of uveal melanoma using a combined approach of resection surgery with brachytherapy. This is a single-center observational retrospective cohort study in which we describe clinical outcomes, complications and survival in 35 cases of melanoma of the iris or the ciliary body after a combination of surgery and brachytherapy or brachytherapy alone. Local treatment of the tumor was successful in all cases with surgery and brachytherapy. The most frequent complications were scleromalacia, bullous keratopathy, retinal toxicity, cataracts, hypotonia, and photophobia. There were three cases of recurrence, all of which were found in the group of patients who had received brachytherapy alone, and in one case we had to perform a secondary enucleation due to tumor growth after brachytherapy. At present, only one patient has died during follow-up due to liver metastases six years after the start of treatment. In carefully selected patients, this approach can be effective and safe, as long as a close follow-up is carried out after surgery

Renal function and choroidal thickness using swept-source optical coherence tomography in diabetic patients

[Aim] To assess the relationship between choroidal thickness and renal function in diabetic patients.[Methods] Cross-sectional retrospective clinical study of 42 eyes of 21 ocular treatment-na?ve diabetic patients. Demographic data included: age, sex, type and course of diabetes. Ocular data included: severity of diabetic retinopathy; retinal thickness at the central macular region, as well as choroidal thickness at the central and paracentral quadrants, using automatically generated maps by swept-source optical coherence tomography; presence of cystic macular edema; and ocular axial length (AXL). Lab-test parameters included: glycated hemoglobin (HbA1c), albuminuria, albumin/creatinine ratio in urine, and glomerular filtration rate.[Results] A significant negative correlation was mainly observed between several choroidal thicknesses, age (P<0.020) and ocular AXL (P<0.030). On the contrary, a significant positive correlation was found between all choroidal thicknesses, HbA1c (P<0.035) and albuminuria (P<0.040).[Conclusion] Choroidal thickness can represent an additional tool to help clinicians predicting the renal status in ocular treatment-naïve diabetic patients.OFTARED “RD16/0008/0010”, funded by Instituto de Salud Carlos III, integrated in the national I+D+i 2013-2016 and co-funded by European Union (ERDF/ESF, “Investing in your future”)

Biocompatibility study of a commercial printed circuit board for biomedical applications: Lab-on-PCB for organotypic retina cultures

Printed circuit board (PCB) technology is well known, reliable, and low-cost, and its application to biomedicine, which implies the integration of microfluidics and electronics, has led to Lab-on-PCB. However, the biocompatibility of the involved materials has to be examined if they are in contact with biological elements. In this paper, the solder mask (PSR-2000 CD02G/CA-25 CD01, Taiyo Ink (Suzhou) Co., LTD., Suzhou, China) of a commercial PCB has been studied for retinal cultures. For this purpose, retinal explants have been cultured over this substrate, both on open and closed systems, with successful results. Cell viability data shows that the solder mask has no cytotoxic effect on the culture allowing the application of PCB as the substrate of customized microelectrode arrays (MEAs). Finally, a comparative study of the biocompatibility of the 3D printer Uniz zSG amber resin has also been carried out.This research was funded by Fondo Europeo de Desarrollo Regional (FEDER) and Consejería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucía (Programa Operativo FEDER 2014–2020), Lab-on-chip de electro-estimulación, para el estudio In-vitro de Cultivos de retina de Larga duración: Retina-on-a-chip project number US-1265983 (Universidad de Sevilla)

Electrostimulation in an autonomous culture lab-on-chip provides neuroprotection of a retinal explant from a retinitis pigmentosa mouse-model

In this paper an autonomous culture system with the capability to electrostimulate organotypic cultures is described, and its utility is demonstrated by the neuroprotection achieved in retinal explants. The system is composed of a lab-on-chip (LOC), an electronic circuit and a data acquisition device. The LOC, in which the culture takes place, includes a microelectrode array (MEA), consisting of a PCB with a group of gold microelectrodes embedded in polydimethylsiloxane (PDMS), a microheater, a thermistor and a microfluidic circuit made of thermoplastic for feeding with culture medium. A plug made of PDMS has been included to facilitate the assembly of the culture LOC, the placement of the mouse retinas inside the MEA and the flow of culture medium. The transparency of the PDMS permits optical applications and a real time monitoring. An electronic circuit allows for a close monitoring of the experiment using a LabVIEW software specifically developed for this setting, including temperature control, heating and electrostimulation. In the experimental conditions, the retinal explants from retinitis pigmentosa mouse-models are dissected the day before neurodegeneration starts, when photoreceptor cell death is expected to progress along the following days, and cultured inside the LOC, using a fluorophore as a live-dead marker. The stimulation is a biphasic square signal of 0.5 Vpp and it is applied for five minutes every other day. Unstimulated RP explants and healthy retinas are used as controls. After seven days, a histological study is performed. We have demonstrated the applicability of this system as an organotypic culture LOC to test the effect of electrostimulation in retinal explants from different mouse models, and found a protective effect on photoreceptor cell death in the conditions tested.This work was supported by the Spanish Ministry of Science and Innovation (project TEC2014-54449-C3-2-R, BIOLOP), by ISCIII (Miguel Servet-I, 2015) cofinanced by the European Regional Development Fund (ERDF) (CP15/00071) and the Andalusian Health Ministry (Fundacion Publica Andaluza Progreso y Salud)

Clinical Outcomes after Surgical Resection Combined with Brachytherapy for Uveal Melanomas

Currently, brachytherapy is the most commonly used therapeutic approach for uveal melanomas. Surgical resection by means of endoresection or exoresection is an alternative approach. The present report recounts our experience over 15 years in the treatment of uveal melanoma using a combined approach of resection surgery with brachytherapy. This is a single-center observational retrospective cohort study in which we describe clinical outcomes, complications and survival in 35 cases of melanoma of the iris or the ciliary body after a combination of surgery and brachytherapy or brachytherapy alone. Local treatment of the tumor was successful in all cases with surgery and brachytherapy. The most frequent complications were scleromalacia, bullous keratopathy, retinal toxicity, cataracts, hypotonia, and photophobia. There were three cases of recurrence, all of which were found in the group of patients who had received brachytherapy alone, and in one case we had to perform a secondary enucleation due to tumor growth after brachytherapy. At present, only one patient has died during follow-up due to liver metastases six years after the start of treatment. In carefully selected patients, this approach can be effective and safe, as long as a close follow-up is carried out after surgery

Subretinal Transplant of Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium on Nanostructured Fibrin-Agarose

Damage to the retinal pigment epithelium (RPE) in age-related macular degeneration and other diseases results in photoreceptor cell death and blindness. Replacement of RPE is therefore being explored as a therapy for several retinal diseases. To move toward a future personalized autologous transplant approach, we have prepared a biocompatible implant using RPE derived from induced pluripotent stem cells (iPSCs) reprogrammed from a healthy donor's monocytes. The correct positioning of the polarized RPE is essential to fulfill its role and protect photoreceptors from degeneration. Hence, we have used a biocompatible hydrogel matrix of fibrin and agarose that allows the surgical placement of an RPE sheet in the subretinal space, keeping its functional orientation. Our aim was to demonstrate safety and viability of the transplant in preclinical models. Pigs were used to test the feasibility of a regular vitreoretinal surgery. Our results show that this implant is suitable for subretinal transplantation allowing human RPE cells to survive and maintain their phenotype and orientation without any local or systemic adverse events. The ability to transplant the iPSC-derived RPE sheet in its natural orientation will surely increase the chance to obtain a therapeutic effect in future translational studies. In the promising field of cellular therapy for retinal degenerative diseases, a new biomaterial is proposed as a scaffold to grow and surgically introduce a monolayer of retinal pigment epithelial cells into the subretinal space, keeping the orientation of the cells for a proper functional integration of the transplant. The use of induced pluripotent stem cells as the starting material for retinal pigment epithelial cells is intended to advance toward a personalized medicine approach.Study supported by Consejería de Salud, Junta de Andalucía and by ISCIII (Miguel Servet-I, 2015) cofinanced by European Regional Development Fund (ERDF) (CP/00071)