[Artificial intelligence and its applications in medicine I: introductory background to AI and robotics]. / La inteligencia artificial y sus aplicaciones en medicina I: introducción antecedentes a la IA y robótica.

Technology and medicine follow a parallel path during the last decades. Technological advances are changing the concept of health and health needs are influencing the development of technology. Artificial intelligence (AI) is made up of a series of sufficiently trained logical algorithms from which machines are capable of making decisions for specific cases based on general rules. This technology has applications in the diagnosis and follow-up of patients with an individualized prognostic evaluation of them. Furthermore, if we combine this technology with robotics, we can create intelligent machines that make more efficient diagnostic proposals in their work. Therefore, AI is going to be a technology present in our daily work through machines or computer programs, which in a more or less transparent way for the user, will become a daily reality in health processes. Health professionals have to know this technology, its advantages and disadvantages, because it will be an integral part of our work. In these two articles we intend to give a basic vision of this technology adapted to doctors with a review of its history and evolution, its real applications at the present time and a vision of a future in which AI and Big Data will shape the personalized medicine that will characterize the 21st century.

Effectiveness of a chat-bot for the adult population to quit smoking: protocol of a pragmatic clinical trial in primary care (Dejal@).

BACKGROUND: The wide scale and severity of consequences of tobacco use, benefits derived from cessation, low rates of intervention by healthcare professionals, and new opportunities stemming from novel communications technologies are the main factors motivating this project. Thus, the purpose of this study is to assess the effectiveness of an intervention that helps people cease smoking and increase their nicotine abstinence rates in the long term via a chat-bot, compared to usual practice, utilizing a chemical validation at 6 months. METHODS: Design: Randomized, controlled, multicentric, pragmatic clinical trial, with a 6-month follow-up. SETTING: Healthcare centers in the public healthcare system of the Community of Madrid (Madrid Regional Health Service). PARTICIPANTS: Smokers > 18 years of age who attend a healthcare center and accept help to quit smoking in the following month. N = 460 smokers (230 per arm) who will be recruited prior to randomization. Intervention group: use of a chat-bot with evidence-based contents to help quit smoking. CONTROL GROUP: Usual treatment (according to the protocol for tobacco cessation by the Madrid Regional Health Service Main variable: Continuous nicotine withdrawal with chemical validation (carbon monoxide in exhaled air). Intention-to-treat analysis. Difference between groups in continuous abstinence rates at 6 months with their corresponding 95% confidence interval. A logistic regression model will be built to adjust for confounding factors. RESULTS: First expected results in January 2020. DISCUSSION: Providing science-based evidence on the effectiveness of clinical interventions via information technologies, without the physical presence of a professional, is essential. In addition to being more efficient, the characteristics of these interventions can improve effectiveness, accessibility, and adherence to treatment. From an ethics perspective, this new type of intervention must be backed by scientific evidence to circumvent pressures from the market or particular interests, improve patient safety, and follow the standards of correct practices for clinical interventions. TRIAL REGISTRATION: ClinicalTrials.gov, reference number NCT03445507.

An experience in integrated management of clinical risks.

BACKGROUND: Manage clinical risks under the integrated risk management model of the BUPA organization (British United Provident Association). MATERIALS AND METHODS: BUPA is an international group that provides health insurance and healthcare services. The project has been limited to Europe and Latin America (ELA) and this article presents the results related to hospitals. The integral risk management model was based on a governance structure, a risk management framework and the risk management itself (continuous process of identification, evaluation, management, monitoring and reporting). For the latter, a catalog of potential clinical risks was drawn up, using the Joint Commission International (JCI) standards as a reference and applied to a hospital to identify the risk to which they were exposed in their daily activity. An evaluation was conducted, based on its impact and probability of occurrence and depending on the residual and inherent score obtained, the action on each risk and the effectiveness of the controls were determined. A continuous monitoring of the risk profile and the information to share with the Board was defined. RESULTS: The catalog consisted of 126 risks and 479 controls, divided by areas of application. In the assessment of the inherent risk, 84% of the risks were at an acceptable and assumable level, and in 16% it was necessary to establish an action plan. CONCLUSIONS: Under the conditions of the study, we believe the benefits of implementing an integrated management of clinical risk system consisted in providing services that meet the legal requirements and standards of good practice (in our case, the JCI's standards). They allowed us to advance in the organization's management of, improving its efficiency in the allocation of resources for risk management and adaptation to the environment and the patient. In addition, this strategy can facilitate decision-making and encourage the organization's transformation capacity.

Cancer vaccine characterization: from bench to clinic.

BACKGROUND: The development of safe, effective, and affordable vaccines has become a global effort due to its vast impact on overall world health conditions. A brief overview of vaccine characterization techniques, especially in the area of high-resolution mass spectrometry, is presented. It is highly conceivable that the proper use of advanced technologies such as high-resolution mass spectrometry, along with the appropriate chemical and physical property evaluations, will yield tremendous in-depth scientific understanding for the characterization of vaccines in various stages of vaccine development. This work presents the physicochemical and biological characterization of cancer vaccine Racotumomab/alumina, a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH)3, in several clinical trials for melanoma, breast, and lung cancer. METHODS: Racotumomab was obtained from ascites fluid, transferred to fermentation in stirred tank at 10 L and followed to a scale up to 41 L. The mass spectrometry was used for the determination of intact molecule, light and heavy chains masses; amino acids sequence analysis, N- and C-terminal, glycosylation and posttranslational modifications. Also we used the DLS for the size distribution and zeta potential analysis. The biological analyses were performed in mice and chickens. RESULTS: We observed differences in glycosylation pattern, charge heterogeneity and structural stability between in vivo-produced and bioreactor-obtained Racotumomab products. Interestingly, these modifications had no significant impact on the immune responses elicited in two different animal models. CONCLUSIONS: We are demonstrated that this approach could potentially be more efficient and effective for supporting vaccine research and development.

Outcome of patients with acute promyelocytic leukemia failing to front-line treatment with all-trans retinoic acid and anthracycline-based chemotherapy (PETHEMA protocols LPA96 and LPA99): benefit of an early intervention.

To determine prognosis of acute promyelocytic leukemia (APL) failing to front-line therapy with all-trans retinoic acid (ATRA) and anthracyclines, outcome of 52 patients (32 M/20 F; age: 37, 3-72) included in PETHEMA trials LPA96 and LPA99 who presented with either molecular failure (MOLrel, n=16) or hematological relapse (HEMrel, n=36) was analyzed. Salvage therapy consisted of ATRA and high-dose ara-C-based chemotherapy (HDAC) in most cases (83%), followed by stem-cell transplantation (autologous, 18; allogeneic, 10; syngeneic, 1). Fourteen patients with MOLrel (88%) achieved second molecular complete response (molCR), whereas 81% HEMrel patients responded to second-line treatment, with 58% molCR. After median follow-up of 45 months, four MOLrel and 18 HEMrel patients, respectively, experienced a second relapse. Outcome after MOLrel compared favorably to HEMrel, with longer survival (5-year survival: 64+/-14 vs 24+/-8%, P=0.01) and lower relapse risk (5-year relapse risk: 30+/-13 vs 64+/-9%; P=0.044). Additionally, age

Relapse of chronic myeloid leukemia after allogeneic stem cell transplantation: outcome and prognostic factors: the Chronic Myeloid Leukemia Subcommittee of the GETH (Grupo Español de Trasplante Hemopoyético).

In order to analyze the outcome of patients with chronic myeloid leukemia (CML) who relapse after allogeneic stem cell transplantation (SCT), we investigated data from 107 patients reported to the Spanish Registry, GETH. In all, 93 (87%) patients were treated after relapse; 36 out of 49 that failed to achieve a response received a second relapse-treatment, and seven a third one. At the last follow-up, the number of patients in molecular or cytogenetic remission was 29 and 13, respectively. Overall survival and progression-free survival after relapse were 53.6% (95% CI: 42.9--64.2) and 52% (95% CI: 41-63) at 5 years, respectively. In multivariate analysis, survival was significantly related to CML phase at relapse (cytogenetic or chronic phase vs advanced phases) and time from transplant to relapse (<1 vs >or=1 year). Patients with no adverse factors had a better survival compared with patients with one or two adverse features (65 vs 35 vs 0%, respectively). We conclude that a significant proportion of CML patients that relapse after transplantation can regain complete and long-lasting remissions with one or more salvage therapies. Disease stage at relapse and time from transplant to relapse should be taken into account when comparing results of different salvage treatments.

Advantages of flow cytometry immunophenotyping for the diagnosis of central nervous system non-Hodgkin's lymphoma in AIDS patients.

BACKGROUND: Neurological disorders are common in HIV-infected patients. Central nervous system (CNS) lymphoma should always be considered because it is an important cause of morbidity and mortality. OBJECTIVES: To investigate the clinical utility of flow cytometry immunophenotyping (FCI) in diagnosing or discarding leptomeningeal involvement in HIV-infected patients and to compare its sensitivity with that of conventional cytological methods. METHODS: Fifty-six cerebrospinal fluid (CSF) samples from 29 HIV-infected patients were independently evaluated by flow cytometry and cytology. The description of an aberrant immunophenotype was the criterion used to define the malignant nature of any CSF cell population. RESULTS: FCI and cytology gave concordant results for 48 of the 56 CSF samples studied: 37 were negative for malignancy and 11 had evidence of CNS lymphoma. Discordant results were obtained for eight CSF samples, and the accuracy of the FCI findings could be demonstrated for four CSF samples described as positive for malignancy according to the FCI criteria. CONCLUSIONS: A high level of agreement was found between the results obtained using the two methods, but FCI gave at least 25% higher sensitivity than conventional cytomorphological methods for the detection of malignant cells. This advantage suggests that, in case of negative flow cytometry results, disorders other than non-Hodgkin's lymphoma should be strongly considered.

[Prothrombotic factors in stroke]. / Factores protrombóticos en la enfermedad cerebrovascular isquémica.

INTRODUCTION: Factor V Leiden and prothrombin 20210A polymorphisms are the most common mutations related to deep vein thrombosis, however their relationship with stroke is debated. This paper studies the possible relationship between both entities. MATERIAL AND METHODS: A case-control study was conducted during 27 months to study their association. A total of 312 stroke cases were included, 73 were under 60 years. Control group was obtained from blood donors. Factor V Leiden and prothrombin 20210A polymorphism prevalence was studied. Results were analyzed according to the age and the type of stroke (TOAST classification, 1993). RESULTS: Factor V Leiden was not related to stroke in the general population (OR: 0.65; 95 % CI: 0.18-2.27). The study according to age did not show any association (younger than 60 years: OR: 1.12; 95 % CI: 0.21-5.90; older than 60 years: OR: 0.50; 95 % CI: 0.11-2.14). However, prothrombin 20210A polymorphism OR in cases under 60 was OR: 2.92; 95 % CI: 0.71-11.92 suggesting a possible association between this mutation and stroke. There was no association in the general population (OR: 2.0; 95 % CI: 0.63-6.29) or in people over 60 (OR: 1.73; 95 % CI: 0.51- 5.83). The analysis according to stroke subtype did not show any association in the distribution of any of the polymorphisms studied. CONCLUSION: This study suggests that prothrombin 20210A polymorphism may play a role in stroke under 60 years of age. Factor V Leiden does not seem to be related to stroke.

Low transplant-related mortality after second allogeneic peripheral blood stem cell transplant with reduced-intensity conditioning in adult patients who have failed a prior autologous transplant.

Standard allogeneic stem cell transplantation (SCT) has been associated with a high transplant-related mortality (TRM) in patients who have failed a prior autologous SCT (ASCT). Reduced-intensity conditioning (RIC) regimens may reduce the toxicities and TRM of traditional myeloablative transplants. We report 46 adults who received a RIC peripheral blood SCT from an HLA-identical sibling in two multicenter prospective studies. The median interval between ASCT and allograft was 16 months, and the patients were allografted due to disease progression (n = 43) and/or secondary myelodysplasia (n = 4). Conditioning regimens consisted of fludarabine plus melphalan (n = 41) or busulphan (n = 5). The 100-day incidence of grade II-IV acute graft-versus-host disease (GVHD) was 42% (24% grade III-IV), and 10/30 evaluable patients developed chronic extensive GVHD. Early complete donor chimerism in bone marrow and peripheral blood was observed in 35/42 (83%) patients, and 16 evaluable patients had complete chimerism 1 year post transplant. With a median follow-up of 358 days (450 in 29 survivors), the 1-year incidence of TRM was 24%, and the 1-year overall (OS) and progression-free survival were 63% and 57%, respectively. Patients who had chemorefractory/ progressive disease, a low performance status or received GVHD prophylaxis with cyclosporine A alone (n = 32) had a 1-year TRM of 35% and an OS of 46%, while patients who had none of these characteristics (n = 32) had a 1-year TRM of 35% and an OS of 46% while patients who had none of these characteristics (n = 14) had a TRM of 0% and an OS of 100%. Our results suggest that adult patients who fail a prior ASCT can be salvaged with a RIC allogeneic PBSCT with a low risk of TRM, although patient selection has a profound influence on early outcome.

Report of three cases of circulating heparin-like anticoagulants.

Clinically significant endogenous circulating heparin-like anticoagulant activity has been associated with hematological malignancies, liver damage, and other pathological conditions. The source of high plasma concentrations of endogenous heparin-like anticoagulants is poorly understood. We report three cases of circulating heparin-like anticoagulants in three patients with hematological malignancies: CLL, multiple myeloma, and T-prolymphocytic leukemia. The severity of bleeding in our patients ranged from severe epistaxis and deep-site hematoma to bleeding of biopsy site and occasional ecchymosis.

Expression of factor VII in the liver of patients with liver disease: correlations with the disease severity and impairment in the hemostasis.

Factor VII (FVII) plasma levels in patients with liver disease may be below the normal range. However, no data are available on FVII expression in liver biopsies from patients with liver diseases other than cirrhosis. We have analyzed the expression of FVII by in situ hybridization in liver biopsies from 50 patients in comparison with the procoagulant activity of FVII, and with the plasma levels as activated FVII (FVIIa) and FVII antigen. The level of FVIIa was significantly lower in stage 4 liver fibrosis patients than in the remaining ones (P < 0.05). The percentage of hepatocytes expressing FVII was significantly lower in stage 4 liver fibrosis patients (4.1+/-1.3%) than in stage 3 (22.7+/-6.1%), stage 2 (31.5+/-6.1%), stage 1 (43.7+/-8.2%) and stage 0 patients (63.8+/-4.4%) (P < 0.001). These percentages correlated inversely in a statistically significant way with the histological activity index and the liver function tests. We have demonstrated that the FVIIa plasma levels in patients with chronic liver disease other than cirrhosis may be below the normal range in the absence of blood coagulation impairment. The percentage of hepatocytes expressing FVII decreases as the severity of liver damage increases.

Atypical chronic graft-versus-host disease following interferon therapy for chronic myeloid leukaemia relapsing after allogeneic BMT.

We report a 54-year-old woman who received interferon alpha for haematological relapse of Ph-positive CML, 7 years after allogeneic BMT from an HLA-identical brother. Eighteen months after relapse, cytogenetic and molecular remission was achieved. She received interferon therapy for 25 months and it was discontinued when she developed skin lesions on her face and trunk, dysphagia and fever with respiratory failure and bilateral patchy airspace consolidation of the lung without microbiologic findings. Histologic features showed discoid lupus erythematosis, oesophagitis with pseudomembranes and a mixed pattern of lymphocytic bronchiolitis involving the alveoli and interstitial spaces all compatible with chronic GVHD. The patient was commenced on immunosuppressive therapy with complete clinical and radiological resolution. The available evidence supports an atypical presentation of chronic GVHD and suggests a role for interferon alpha in the pathogenesis of GVHD. To the best of our knowledge, this is the first case reported of severe chronic GVHD occurring during the course of interferon therapy for relapsed CML.

¿Tenemos el enemigo en casa? El niño y la televisión / Are we living with the enemy? The child and television

La comunicación es el proceso de transmisión y recepción de ideas, información y mensajes. Se lleva a cabo a través de unos medios propios, los medios de comunicación; en los últimos veinte años, sobre todo, se caracteriza por la disminución de los tiempos de transmisión de la información a distancia y del mayor acceso a dicha información. Los medios de comunicación influyen en todas las edades, pero de una manera especial en la infancia y la adolescencia, y pueden llegar a ser, sobre todo la televisión (TV), el sustituto de los padres y el principal profesor de los niños, llegando en ocasiones el tiempo de TV a superar el escolar' y con un impacto muy importante en la salud y la conducta de la infancia2. Hemos realizado una búsqueda bibliográfica, de forma especial en internet, sobre la influencia de todos los medios, pero a efectos didácticos, fundamentalmente de la TV, por ser el más importante en la infancia y en la adolescencia (AU)