Microenvironment M1/M2 macrophages and tumoral progression vary within C57BL/6 mice from same substrain in prostate cancer model.

Cancer mice models are critical for immune-oncology research; they provide conditions to explore tumor immunoenviroment aiming to advance knowledge and treatment development. Often, research groups breed their own mice colonies. To assess the effect of C57BL/6 mice breeding nuclei in prostate cancer development and intratumoral macrophage populations, an isotransplantation experiment was performed. C57BL/6J mice from two breeding nuclei (nA and nB) were employed for prostate adenocarcinoma TRAMP-C1 cell implantation; tumor growth period and intratumoral macrophage profile were measured. BL/6nB mice (54%) showed tumor implantation after 69-day growth period while BL/6nA implantation reached 100% across tumor growth period (28 days). No difference in total macrophage populations was observed between groups within several tumoral regions; significantly higher M2 macrophage profile was observed in tumor microenvironments from both mice groups. Nevertheless, BL/6nB tumors showed around twice the population of M1 profile (11-27%) than BL6nA (4-15%) and less non-polarized macrophages. The M1:M2 average ratio was 1:8 for group A and 1:4 for B. Our results demonstrate different tumor progression and intratumoral macrophage populations among mice from the same substrain. Data obtained in this study shows the relevance of animal source renewal for better control of murine cancer model variables.

Prognostic performance of neutrophil/lymphocyte ratio and platelet/lymphocyte ratio for mortality in patients with acute stroke / Rendimiento pronóstico de la razón neutrófilos/linfocitos y la razón plaquetas/linfocitos para la mortalidad en pacientes con ictus agudo

Objective: To evaluate the prognostic performance of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) for mortality in patients with acute stroke treated at a Peruvian hospital. Design: Retrospective cohort study. Setting: Tertiary care hospital. Patients: Patients aged ≥18 years with a diagnosis of acute stroke and admitted to the hospital from May 2019 to June 2021. Interventions: None. Main variables of interests: Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mortality. Results: A total of 165 patients were included. The mean age was 66.1±14.2 years, and 59.4% were male. Only NLR had a performance superior to 0.7 (AUC: 0.75; 95%CI: 0.65–0.85), and its elevated levels were associated with an increased risk of mortality (aRR: 3.66; 95%CI: 1.77–8.85) after adjusting for confounders. Conclusion: The neutrophil-to-lymphocyte ratio has an acceptable prognostic performance for mortality in patients with acute stroke. Its use may be considered to stratify patients’ risk and to consider timely alternative care and management.(AU)

Objetivo: Evaluar el desempeño pronóstico de la relación neutrófilos-linfocitos (NLR) y la relación plaquetas-linfocitos (PLR) para la mortalidad en pacientes con stroke agudo tratados en un hospital peruano. Diseño: Estudio de cohorte retrospectivo. Ámbito: Hospital de atención terciaria. Participantes: Pacientes ≥18 años con diagnóstico de stroke agudo e ingresados en el hospital entre mayo de 2019 y junio de 2021. Intervenciones: Ninguna. Variables de interés principales: Razón neutrófilos/linfocitos, razón plaquetas/linfocitos y mortalidad. Resultados: Se incluyeron un total de 165 pacientes. La edad media fue de 66,1±14,2 años, y el 59,4% eran varones. Sólo el NLR tuvo un rendimiento superior a 0,7 (AUC: 0,75; IC95%: 0,65-0,85), y sus niveles elevados se asociaron con un mayor riesgo de mortalidad (RRa: 3,66; IC95%: 1,77-8,85) tras ajustar por factores de confusión. Conclusiones: La razón neutrófilos/linfocitos tiene un rendimiento pronóstico aceptable para la mortalidad en pacientes con stroke. Su uso puede ser considerado para estratificar el riesgo de los pacientes y considerar oportunamente cuidados y manejo alternativos.(AU)

Prognostic performance of neutrophil/lymphocyte ratio and platelet/lymphocyte ratio for mortality in patients with acute stroke.

OBJECTIVE: To evaluate the prognostic performance of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) for mortality in patients with acute stroke treated at a Peruvian hospital. DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital. PATIENTS: Patients aged ≥18 years with a diagnosis of acute stroke and admitted to the hospital from May 2019 to June 2021. INTERVENTIONS: None. MAIN VARIABLES OF INTERESTS: Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and mortality. RESULTS: A total of 165 patients were included. The mean age was 66.1±14.2 years, and 59.4% were male. Only NLR had a performance superior to 0.7 (AUC: 0.75; 95%CI: 0.65-0.85), and its elevated levels were associated with an increased risk of mortality (aRR: 3.66; 95%CI: 1.77-8.85) after adjusting for confounders. CONCLUSION: The neutrophil-to-lymphocyte ratio has an acceptable prognostic performance for mortality in patients with acute stroke. Its use may be considered to stratify patients' risk and to consider timely alternative care and management.

A cold wave of winter 2021 in central South America: characteristics and impacts.

During the austral winter (June-August) of 2021, the meteorological services of Brazil, Argentina, Peru, Paraguay, Bolivia, and Chile all issued forecasts for unusually cold conditions. Record-low minimum temperatures and cold spells were documented, including one strong cold wave episode that affected 5 countries. In this study, we define a cold wave as a period in which daily maximum and minimum air temperatures are below the corresponding climatological 10th percentile for three or more consecutive days. The intense cold wave event in the last week of June, 2021, resulted in record-breaking minimum daily temperatures in several places in central South America and Chile. Several locations had temperatures about 10 °C below average, central South America had freezing conditions, and southern Brazil even saw snow. The cold air surge was characterized by an intense upper-air trough located close to 35° S and 70° W. The southerly flow to the west of this trough brought very cold air northward into subtropical and tropical South America. A northward flow between the lower-level cyclonic and anticyclonic perturbations caused the intense southerly flow between the upper-level ridge and trough. This condition facilitated the inflow of near-surface cold air from southern Argentina into southeastern Brazil and tropical South America east of the Andes. In the city of São Paulo, the cold wave caused the death of 13 homeless people from hypothermia. Frost and snow across southern and southeastern Brazil caused significant damage to coffee, sugarcane, oranges, grapes, and other fruit and vegetable crops. Wine and coffee production fell, the latter by 30%, and prices of food and commodities in the region rose. Supplementary Information: The online version contains supplementary material available at 10.1007/s00382-023-06701-1.

Estudios de prevalencia del síndrome de apneas obstructivas del sueño en la población adulta / Studies of prevalence of obstructive sleep apnea syndrome in adult population

El síndrome de apnea-hipopnea obstructiva del sueño (SAHOS) es un trastorno respiratorio común asociado con múltiples consecuencias adversas para la salud y su prevalencia ha aumentado en paralelo con el aumento de la obesidad en la población. MÉTODOS: revisión sistemática que examina los estudios de prevalencia de SAHOS en la población general. Se incluyeron los estudios transversales y los componentes transversales de los estudios longitudinales que midieron objetivamente la prevalencia de SAHOS en adultos empleando instrumentos de laboratorio. Se evaluaron cuarenta estudios poblacionales de las 8.876 publicaciones encontradas en la búsqueda sistemática realizada en PubMed y otras bases de datos. RESULTADOS: Se ha observado importantes diferencias metodológicas en los estudios poblacionales, lo cual ha determinado una amplia variación en la prevalencia de SAHOS reportada, con un valor promedio de 36,9% (IC95% 28,3-45,4%) en hombres y 24,0% (IC 95% 16,3-31,6%) en mujeres. Se ha reportado un aumento en la prevalencia de SAHOS en el curso del tiempo desde 1987 hasta el 2020. Esta condición es más prevalente en varones, aumenta progresivamente con la edad y se asocia a la obesidad. La somnolencia diurna excesiva se ha asociado al diagnóstico de SAHOS, pero sólo una fracción de los sujetos con índice de apnea-hipopnea ≥ 5 eventos/hora presentan somnolencia diurna. CONCLUSIÓN: La prevalencia de SAHOS ha aumentado en los estudios poblacionales realizados en el curso del tiempo. La variabilidad reportada en la prevalencia de SAHOS probablemente esté relacionada con los diferentes equipos y definiciones operacionales empleados en el proceso diagnóstico, y las características de los sujetos examinados, incluyendo el importante aumento de la obesidad en la población.

Obstructive sleep apnea syndrome (OSAS) is a common disorder associated with multiple adverse health consequences and its prevalence is increasing in parallel with global rising in obesity. METHODS: We have developed a systematic review to examine obstructive sleep apnea syndrome prevalence studies in adults in the general population. We included the cross-sectional studies and the cross-sectional components of longitudinal studies that objectively measured OSAS in adults using laboratory instruments. Forty studies out of 8,876 articles found by systematically searching in PubMed and other databases were included in this review. RESULTS: Substantial methodological heterogeneity in population prevalence studies has been observed, determining a wide variation in OSAS prevalence defined at an apnea-hypopnea index (AHI) ≥ 5 events/hour, the average OSAS prevalence was 36.9% (CI95% 28.3-45.4%) in men and 24.0% (CI95% 16.3-31.6%) in women. The OSAS prevalence has increased over the time. OSAS is more prevalent in men than in women and increases with age and obesity. Excessive daytime sleepiness has been suggested as the most important symptom associated to OSAS, but only a fraction of subjects with AHI ≥ 5 events/hour report daytime sleepiness. CONCLUSION: The prevalence of OSAS has increased in epidemiological studies over time. The differences in reported prevalence of obstructive sleep apnea are probably due to different diagnostic equipment, operational definitions, study design and characteristics of included subjects, including effects of the obesity epidemic.

[A reflection about the ethical implications of telemedicine]. / Una reflexión ética sobre la telemedicina.

Recognizing the role of technology in the development of medicine and the impact of telecommunication advances, we reflect on the meaning and ethics of the use of Telemedicine, both in its general dimension for the use and distribution of knowledge, as well as in the delivery of health actions, scientific research, and data management. Teleconsultation is discussed in greater detail, analyzing its process and application, reviewing its possible advantages and disadvantages, from the point of view of providers and patients. We highlight the need to carry out an appropriate evaluation of each instance, from the point of view of both the patient and the professional who uses it. The importance of maintaining a doctor-patient relationship in agreement with the nature and practice of Medicine, respecting people's dignity, is emphasized. We mention the ethical conditions that must be bore in mind for the proper use of telemedicine. We discuss the eventual influence that this practice will have on the concept and practice of medical care, while suggesting the need to legislate on the matter.

Isolation and characterization of high affinity and highly stable anti-Chikungunya virus antibodies using ALTHEA Gold Libraries™.

BACKGROUND: More than 3 million infections were attributed to Chikungunya virus (CHIKV) in the 2014-2016 outbreak in Mexico, Central and South America, with over 500 deaths directly or indirectly related to this viral disease. CHIKV outbreaks are recurrent and no vaccine nor approved therapeutics exist to prevent or treat CHIKV infection. Reliable and robust diagnostic methods are thus critical to control future CHIKV outbreaks. Direct CHIKV detection in serum samples via highly specific and high affinity anti-CHIKV antibodies has shown to be an early and effective clinical diagnosis. METHODS: To isolate highly specific and high affinity anti-CHIKV, Chikungunya virions were isolated from serum of a patient in Veracruz, México. After purification and characterization via electron microscopy, SDS-PAGE and binding to well-characterized anti-CHIKV antibodies, UV-inactivated particles were utilized as selector in a solid-phase panning in combination with ALTHEA Gold Libraries™, as source of antibodies. The screening was based on ELISA and Next-Generation Sequencing. RESULTS: The CHIKV isolate showed the typical morphology of the virus. Protein bands in the SDS-PAGE were consistent with the size of CHIKV capsid proteins. UV-inactivated CHIKV particles bound tightly the control antibodies. The lead antibodies here obtained, on the other hand, showed high expression yield, > 95% monomeric content after a single-step Protein A purification, and importantly, had a thermal stability above 75 °C. Most of the antibodies recognized linear epitopes on E2, including the highest affinity antibody called C7. A sandwich ELISA implemented with C7 and a potent neutralizing antibody isolated elsewhere, also specific for E2 but recognizing a discontinuous epitope, showed a dynamic range of 0.2-40.0 mg/mL of UV-inactivated CHIKV purified preparation. The number of CHIKV particles estimated based on the concentration of E2 in the extract suggested that the assay could detect clinically meaningful amounts of CHIKV in serum. CONCLUSIONS: The newly discovered antibodies offer valuable tools for characterization of CHIKV isolates. Therefore, the strategy here followed using whole viral particles and ALTHEA Gold Libraries™ could expedite the discovery and development of antibodies for detection and control of emergent and quickly spreading viral outbreaks.

Una reflexión ética sobre la telemedicina / A reflection about the ethical implications of telemedicine

Recognizing the role of technology in the development of medicine and the impact of telecommunication advances, we reflect on the meaning and ethics of the use of Telemedicine, both in its general dimension for the use and distribution of knowledge, as well as in the delivery of health actions, scientific research, and data management. Teleconsultation is discussed in greater detail, analyzing its process and application, reviewing its possible advantages and disadvantages, from the point of view of providers and patients. We highlight the need to carry out an appropriate evaluation of each instance, from the point of view of both the patient and the professional who uses it. The importance of maintaining a doctor-patient relationship in agreement with the nature and practice of Medicine, respecting people's dignity, is emphasized. We mention the ethical conditions that must be bore in mind for the proper use of telemedicine. We discuss the eventual influence that this practice will have on the concept and practice of medical care, while suggesting the need to legislate on the matter.

A novel method for DNA delivery into bacteria using cationic copolymers.

Amphiphilic copolymers have a wide variety of medical and biotechnological applications, including DNA transfection in eukaryotic cells. Still, no polymer-primed transfection of prokaryotic cells has been described. The reversible addition-fragmentation chain transfer (RAFT) polymer synthesis technique and the reversible deactivation radical polymerization variants allow the design of polymers with well-controlled molar mass, morphology, and hydrophilicity/hydrophobicity ratios. RAFT was used to synthesize two amphiphilic copolymers containing different ratios of the amphiphilic poly[2-(dimethyl-amino) ethyl methacrylate] and the hydrophobic poly [methyl methacrylate]. These copolymers bound to pUC-19 DNA and successfully transfected non-competent Escherichia coli DH5α, with transformation efficiency in the range of 103 colony-forming units per µg of plasmid DNA. These results demonstrate prokaryote transformation using polymers with controlled amphiphilic/hydrophobic ratios.

A novel method for DNA delivery into bacteria using cationic copolymers

Amphiphilic copolymers have a wide variety of medical and biotechnological applications, including DNA transfection in eukaryotic cells. Still, no polymer-primed transfection of prokaryotic cells has been described. The reversible addition-fragmentation chain transfer (RAFT) polymer synthesis technique and the reversible deactivation radical polymerization variants allow the design of polymers with well-controlled molar mass, morphology, and hydrophilicity/hydrophobicity ratios. RAFT was used to synthesize two amphiphilic copolymers containing different ratios of the amphiphilic poly[2-(dimethyl-amino) ethyl methacrylate] and the hydrophobic poly [methyl methacrylate]. These copolymers bound to pUC-19 DNA and successfully transfected non-competent Escherichia coli DH5α, with transformation efficiency in the range of 103 colony-forming units per µg of plasmid DNA. These results demonstrate prokaryote transformation using polymers with controlled amphiphilic/hydrophobic ratios.

[Conscientious objection in medical actions]. / Objeción de conciencia y acciones de salud.

Conscientious Objection arises as a response to a regulation that is judged as immoral. Faced with a law that is considered unfair, the citizen can respond accepting it against his will, exercising conscientious objection on a personal level or, collectively reaching civil disobedience or revolutionary violence. This is an old discussion known since ancient Greece. The current enactment of laws that allow actions previously judged as crime, and that contravene medical tradition, reactivated the discussion about such objection. Some people, such as Savolescu, who denies the legitimacy of conscientious objection invoked by doctors, arguing that it is inefficient, leads to inequality and is inconsistent. He proposes that the values of these professionals can be tolerated privately but should not be determinant in the public sphere. These arguments are critically examined, mentioning pertinent answers from theoretical and practical points of view. We highlight that ethics should not differ in public and private spheres and the principles should be the same, but exercised in different fields. It is concluded that conscientious objection is acquiring legitimacy and that it is necessary to reflect on the underlying reasons that lead to invoke it. It should be considered a civilized resource against determinations of power that are considered to be an attempt against personal values and moral integrity.

Invited Review: Epigenetics in neurodevelopment.

Neural development requires the orchestration of dynamic changes in gene expression to regulate cell fate decisions. This regulation is heavily influenced by epigenetics, heritable changes in gene expression not directly explained by genomic information alone. An understanding of the complexity of epigenetic regulation is rapidly emerging through the development of novel technologies that can assay various features of epigenetics and gene regulation. Here, we provide a broad overview of several commonly investigated modes of epigenetic regulation, including DNA methylation, histone modifications, noncoding RNAs, as well as epitranscriptomics that describe modifications of RNA, in neurodevelopment and diseases. Rather than functioning in isolation, it is being increasingly appreciated that these various modes of gene regulation are dynamically interactive and coordinate the complex nature of neurodevelopment along multiple axes. Future work investigating these interactions will likely utilize 'multi-omic' strategies that assay cell fate dynamics in a high-dimensional and high-throughput fashion. Novel human neurodevelopmental models including iPSC and cerebral organoid systems may provide further insight into human-specific features of neurodevelopment and diseases.

Objeción de conciencia y acciones de salud / Conscientious objection in medical actions

Conscientious Objection arises as a response to a regulation that is judged as immoral. Faced with a law that is considered unfair, the citizen can respond accepting it against his will, exercising conscientious objection on a personal level or, collectively reaching civil disobedience or revolutionary violence. This is an old discussion known since ancient Greece. The current enactment of laws that allow actions previously judged as crime, and that contravene medical tradition, reactivated the discussion about such objection. Some people, such as Savolescu, who denies the legitimacy of conscientious objection invoked by doctors, arguing that it is inefficient, leads to inequality and is inconsistent. He proposes that the values of these professionals can be tolerated privately but should not be determinant in the public sphere. These arguments are critically examined, mentioning pertinent answers from theoretical and practical points of view. We highlight that ethics should not differ in public and private spheres and the principles should be the same, but exercised in different fields. It is concluded that conscientious objection is acquiring legitimacy and that it is necessary to reflect on the underlying reasons that lead to invoke it. It should be considered a civilized resource against determinations of power that are considered to be an attempt against personal values and moral integrity.

Evaluation of the Induction of Cell-Mediated Immunity Against Candida albicans in a Model of Cutaneous Infection in Newborn 0-Day-Old Mice.

Candida albicans is a commensal fungus of the skin and mucous membranes in humans, but it is also responsible for mucocutaneous and systemic infections in immunocompromised patients like low birth weight neonates and premature newborns. The epicutaneous application of C. albicans is widely used to study the immune response against this pathogen in adult mice models. However, the immune response of newborns against infections caused by the genus Candida is poorly understood. In order to mimic premature human infection, we developed a model of C. albicans epicutaneous infection in newborn mice. We found that yeasts were able to colonize while the pseudohyphae invaded the epidermis. Recruitment of polymorphonuclear and mononuclear cells at the infection zone was observed. Fungal invasion, fungal burden and cellular infiltration displayed a time- and dose-dependent response. Interestingly, newborn mice were able to control C. albicans primary infection. Finally, we showed that the epicutaneous infection of C. albicans in newborn mice at birth results in the induction of cell-mediated immunity as evinced by delayed-type hypersensitivity assays.

Where do we aspire to publish? A position paper on scientific communication in biochemistry and molecular biology.

The scientific publication landscape is changing quickly, with an enormous increase in options and models. Articles can be published in a complex variety of journals that differ in their presentation format (online-only or in-print), editorial organizations that maintain them (commercial and/or society-based), editorial handling (academic or professional editors), editorial board composition (academic or professional), payment options to cover editorial costs (open access or pay-to-read), indexation, visibility, branding, and other aspects. Additionally, online submissions of non-revised versions of manuscripts prior to seeking publication in a peer-reviewed journal (a practice known as pre-printing) are a growing trend in biological sciences. In this changing landscape, researchers in biochemistry and molecular biology must re-think their priorities in terms of scientific output dissemination. The evaluation processes and institutional funding for scientific publications should also be revised accordingly. This article presents the results of discussions within the Department of Biochemistry, University of São Paulo, on this subject.

Where do we aspire to publish? A position paper on scientific communication in biochemistry and molecular biology

The scientific publication landscape is changing quickly, with an enormous increase in options and models. Articles can be published in a complex variety of journals that differ in their presentation format (online-only or in-print), editorial organizations that maintain them (commercial and/or society-based), editorial handling (academic or professional editors), editorial board composition (academic or professional), payment options to cover editorial costs (open access or pay-to-read), indexation, visibility, branding, and other aspects. Additionally, online submissions of non-revised versions of manuscripts prior to seeking publication in a peer-reviewed journal (a practice known as pre-printing) are a growing trend in biological sciences. In this changing landscape, researchers in biochemistry and molecular biology must re-think their priorities in terms of scientific output dissemination. The evaluation processes and institutional funding for scientific publications should also be revised accordingly. This article presents the results of discussions within the Department of Biochemistry, University of São Paulo, on this subject.

Patrones de tratamiento con agentes biológicos: Eficacia y sobrevida a largo plazo en pacientes con artritis reumatoidea / Treatment patterns with biological agents: Efficacy and long-term survival in patients with rheumatoid arthritis

En nuestro país existen pocos datos acerca de los patrones de tratamiento y la sobrevida de las Drogas Modificadoras de la Artritis Reumatoidea biológicas (DMARb) en pacientes con Artritis Reumatoidea (AR). El objetivo de nuestro estudio fue estimar la sobrevida del 1° y 2° agente biológico, determinar sus causas de suspensión y evaluar factores que influyan en la sobrevida de estos agentes. Material y métodos: Se realizó un estudio multicéntrico retrospectivo. Se incluyeron pacientes ≥18 años de edad que cumplieran con criterios ACR/EULAR 2010 para AR y que iniciaron su 1° y/o 2° DMARb entre 01/2006 y 06/2017, la recolección de datos se realizó mediante la revisión de historias clínicas. Se consignaron variables sociodemográficas y clínicas. Resultados: Se incluyeron 347 pacientes con edad mediana de 57,8 años, 89,6% mujeres, 96,5% tenían Factor Reumatoideo (FR) positivo. El 53,9% de los pacientes discontinuaron el tratamiento con la 1°DMARb, treinta y ocho pacientes (41,3%) discontinuaron el 2° DMARb. La causa más frecuente de suspensión del primer biológico fue la falta de provisión, mientras que la del segundo biológico fue la ineficacia. Las supervivencias medianas fueron: para la 1° DMARb 31 meses (IC 95%: 21,8-40,1) y para 2° DMARb 11 meses (IC 95%: 4-17,9), no observamos diferencias significativas en la supervivencia entre los distintos agentes, los factores independientemente asociados a menor supervivencia del 1° DMARb fueron el tabaquismo y menor edad y del 2° DMARb fue haber discontinuado el primer agente biológico debido a evento adverso. Conclusión: Las supervivencias medianas del 1° DMARb y del 2° DMARb fueron 2,6 años y menor a 1 año, respectivamente. A diferencia de otras cohortes de países desarrollados, la causa más frecuente de suspensión del primer biológico fue la falta de provisión de la medicación por parte del pagador, mientras que la del segundo biológico fue la ineficacia.

In our country there are few data about the treatment patterns and the survival of the Biologic Disease Modifying Antirheumatic Drugs (bDMARD) in patients with Rheumatoid Arthritis (RA). The objective of our study was to evaluate the survival of the 1st and 2nd biological agent, determine the causes of suspension and factors that influence on the survival of these agents. Material and methods: A retrospective multicenter study was conducted. We included patients ≥18 years of age who met the ACR/EULAR 2010 criteria for RA and who started in 1st and/or 2nd bDMARD between 01/2006 and 06/2017, the data collection was done by reviewing clinical charts The sociodemographic and clinical variables were recorded. Results: We included 347 patients with a median age of 57.8 years, 89.6% women, 96.5% had positive Rheumatoid Factor (RF). 53.9% of patients discontinued treatment with 1st bDMARD, thirty-eight patients (41.3%) discontinued the 2nd bDMARD. The most frequent cause of suspension of the first biological was the lack of provision, while the second biological was inefficacy. The median survivals were: for the 1st bDMARD 31 months (95% CI: 21.8-40.1) and for the 2nd bDMARD 11 months (95% CI: 4-17.9), we did not observe significant differences in survival between the different agents. The independent factors associated with lower survival of the 1st bDMARD were smoking and lower age and the 2nd bDMARD was to have discontinued the first biological agent due to an adverse event. Conclusion: The median survivals of the 1st bDMARD and the 2nd bDMARD were 2.6 years and less than 1 year, respectively. Unlike other cohorts of developed countries the most frequent cause of suspension of the first biological was the lack of provision of the drug by the payer, while the second biological was inefficacy.

Patrones de tratamiento con agentes biológicos, eficacia y sobrevida a largo plazo en pacientes con espondiloartritis axial: Impacto de los factores sociodemográficos en Latinoamérica / Patterns of treatment with biological agents, efficacy and long-term survival in patients with axial spondyloarthritis: Impact of sociodemographic factors in Latin America

Objetivos: Evaluar y comparar la eficacia y la sobrevida a largo plazo de las Drogas Modificadoras de la Enfermedad-biológicas (DME-b) en Espondiloartritis Axial (EsPax) mediante el índice LUNDEX y determinar las variables asociadas a la discontinuación de las mismas. Material y métodos: Estudio multicéntrico de corte transversal. Se incluyeron pacientes con EsPax en tratamiento con DME-b. Se registraron variables sociodemográficas, terapéuticas y clínicas. Se consignaron fechas de inicio del tratamiento con DME-b, tratamiento concomitante, suspensión o cambio de tratamiento, y causas de suspensión. La eficacia terapéutica se definió según BASDAI a los 6, 12 meses y luego anualmente a partir del inicio de la DME-b. Se calculó el índice LUNDEX en estos períodos. Análisis estadístico: Estadística descriptiva. Test de Student y test Chi² o test exacto de Fisher. Curvas de Kaplan-Meier y Log-Rank. Análisis de regresión proporcional de Cox. Resultados: Se estudiaron 101 pacientes con EsPax, 80,2% varones, con una edad mediana de 42 años (RIC 35-54,5) y un tiempo mediano de evolución de la enfermedad de 19,3 años (RIC 9,4-28,8). El 26,7% de los pacientes no tenían seguro de salud. Los agentes anti-TNFα utilizados como 1º DME-b en orden de frecuencia fueron: Etanercept (ETN) 44,6%, Adalimumab (ADA) 41,6%, Infliximab 7,9% y Certolizumab 5,9%. En el 32,7% de los casos, la DME-b se administró en combinación con una droga modificadora de enfermedad convencional. La sobrevida media fue de 66,2 meses (IC 95%: 51,8-80,5). Debido a que ETN y ADA se utilizaron en el 85% de los pacientes estudiados, se realizaron comparaciones solamente entre estos agentes. El tiempo medio de supervivencia acumulada fue significaticamente menor para ETN versus ADA (X 53,18±8,8 vs X 74,8±8,9, Log-Rank p=0,02), siendo la causa principal de suspensión, la falta de provisión de la medicación. El tiempo promedio de supervivencia para aquellos que no tenían seguro de salud fue significativamente menor X 31,9 meses (IC 95%: 19-45) con respecto a aquellos pacientes con dicho seguro X 72,3 meses (IC 95%: 55,3-89,3), p=0,03. Luego de ajustar por factores confundidores, la falta de un seguro de salud fue la única variable asociada en forma independiente con menor supervivencia del DME-b (HR 2,54, IC 95%: 1,18-5,75). El LUNDEX global fue del 52,7% a los 6 meses y del 46,9% a los 12 meses. Conclusiones: La sobrevida promedio del 1º DME-b fue de 5,5 años. La falta de cobertura de salud fue la única variable que influyó negativamente en la sobrevida del tratamiento con el 1º DME-b en pacientes con EsPax.

Objectives: To evaluate and compare the efficacy and long-term survival of biological disease-modifying drugs (b-DMARDs) in Axial Spondyloarthritis (axSpA) using the LUNDEX index and to determine the variables associated with the discontinuation of these drugs. Material and methods: Cross-sectional multicenter study. Patients with axSpA in treatment with b-DMARDs were included. Sociodemographic, therapeutic and clinical variables were recorded. The dates of initiation of treatment with b-DMARDs, concomitant treatment, suspension or change of treatment, and causes of suspension were recorded. Therapeutic efficacy was defined according to BASDAI at 6, 12 months and then annually from the initiation of b-DMARDs. The LUNDEX index was calculated in these periods. Statistical analysis: Descriptive statistics. Student's test and Chi² test or Fisher's exact test. Curves of Kaplan-Meier and Log-Rank. Proportional regression analysis of Cox. Results: 101 patients with axSpA were studied, 80.2% men, with a median age of 42 years (IQR 35-54.5) and a median disease duration of 19.3 years (IQR 9.4-28.8). 26.7% of patients didn´t have health insurance. The frequency of the anti-TNFα agent used as 1st b-DMARD was: Etanercept (ETA) 44.6%, Adalimumab (ADA) 41.6%, Infliximab 7.9%, and Certolizumab 5.9%. In 32.7% of the cases, the b-DMARD was administered in combination with a c-DMARD (conventional disease-modifying drug). The mean survival was 66.2 months (95% CI: 51.8-80.5). As ETA and ADA were used in 85% of the patients, comparisons were made only between these two agents. The mean survival time was significantly lower for ETA vs ADA (X 53.18 ±8.8 vs X 74.8±8.9, Log-Rank p=0.02), being the main cause of suspension, the lack of drug provision. The average survival time for those who didn´t have health insurance was significantly lower X 31.9 months (95% CI: 19-45) in comparison to those patients who had health insurance X 72.3 months (95% CI: 55.3-89.3), p=0.03. After adjusting for confounding factors, the lack of health insurance was the only variable independently associated with a lower survival of the b-DMARD (HR 2.54, 95% CI: 1.18 to 5.75). The global LUNDEX was 52.7% at 6 months and 46.9% at 12 months. Conclusions: The average survival of the 1st b-DMARD was 5.5 years. The lack of health insurance was the only variable that negatively influenced the survival of the treatment with the 1st b-DMARD in patients with axSpA.

Patrones de tratamiento, sobrevida y efectividad a largo plazo de agentes biológicos en pacientes con Artritis Psoriásica / Patterns of treatment, survival and long-term effectiveness of biological agents in patients with Psoriatic Arthritis

Objetivos: Evaluar los patrones de tratamiento de las DME-b (Drogas Modificadoras de la Enfermedad-biológicas), su sobrevida acumulada y su eficacia a largo plazo en pacientes con Artritis Psoriásica (APs) utilizando el índice LUNDEX. Materiales y métodos: Estudio multicéntrico retrospectivo. Se incluyeron pacientes con diagnóstico de APs que hayan iniciado tratamiento con DME-b. Se recolectaron datos sociodemográficos y clínicos. Se consignaron fechas de inicio de DME-b, tratamiento concomitante, suspensión o cambio de tratamiento, y razones de suspensión. La respuesta terapéutica se definió acorde a MDA (Minimal Disease Activity), a los 6, 12 meses y anualmente a partir del inicio de DME-b. Análisis estadístico: Test de Student y Chi². Curvas de Kaplan Meier y Log Rank. Análisis de regresión de Cox. Resultados: Se incluyeron 72 pacientes con APs, 39 (54,2%) de sexo masculino. La edad mediana fue de 54,5 años (RIC 45-61) y el tiempo mediano de evolución de la enfermedad de 11 años (RIC 6-15). 71,2% (n=42) presentaron comorbilidades. El primer DME-b fue en orden decreciente de frecuencia: Adalimumab (45,8%), Etanercept (36,1%), Certolizumab (5,6%), Infliximab (4,2%), Ustekinumab (4,2%), Abatacept (2,7%) y Golimumab (1,4%). 15 pacientes (25,4%) recibieron DME-b en monoterapia. La sobrevida media fue de 82 meses (DE±7,4). El LUNDEX del primer biológico fue 24,7% a los 6 meses y 44,3% al año. La sobrevida media de Adalimumab fue de 90 meses (DE±10,4) y de Etanercept 79 meses (DE±12). Los pacientes añosos presentaron menor sobrevida de la droga [≥55 años: X59,8 (DE±10,5) vs <55 años: X101,2 (DE±9,7), p=0,006]. Luego de ajustar por diferentes confundidores, la edad ≥55 años se mantuvo significativamente a menor sobrevida [HR=1,064 (IC=1,01-1,11) p=0,005]. El LUNDEX fue menor en obesos vs no obesos (16% vs 66% al año, p=0,89; 10,5 vs 74,9% a los 2 años, p=0,011 y 5,9 vs 81,8% a los 3 años, p=0,005). Conclusiones: La sobrevida promedio del primer DME-b fue de 6,8 años. La única variable asociada a menor sobrevida fue la mayor edad.

Objectives: To evaluate the treatment patterns of DME-b (Disease-Modifying Drugs-biological), their accumulated survival and their long-term efficacy in patients with psoriatic arthritis (PsA) using the LUNDEX index. Materials and methods: Retrospective multicentre study. We included patients diagnosed with PsA who started treatment with DME-b. Sociodemographic and clinical data were collected. BMI-D start dates, concomitant treatment, suspension or change of treatment, and reasons for suspension were recorded. The therapeutic response was defined according to MDA (Minimal Disease Activity), at 6, 12 months and annually from the beginning of DME-b. Statistical analysis: Student test and Chi². Curves of Kaplan Meier and Log Rank. Cox regression analysis. Results: We included 72 patients with PsA, 39 (54.2%) male. The median age was 54.5 years (IQR 45-61) and the median time of evolution of the disease was 11 years (IQR 6-15). 71.2% (n=42) presented comorbidities. The first DME-b was in decreasing order of frequency: Adalimumab (45.8%), Etanercept (36.1%), Certolizumab (5.6%), Infliximab (4.2%), Ustekinumab (4.2%), Abatacept (2.7%) and Golimumab (1.4%). 15 patients (25.4%) received DME-b monotherapy. The mean survival was 82 months (SD±7.4). The LUNDEX of the first biological was 24.7% at 6 months and 44.3% per year. The mean survival of Adalimumab was 90 months (SD±10.4) and Etanercept 79 months (SD±12). Older patients had a lower survival of the drug [≥55 years: X59.8 (SD±10.5) vs <55 years: X101.2 (SD±9.7), p=0.006]. After adjusting for different confounders, age ≥55 years was significantly maintained at lower survival [HR=1.064 (CI=1.01-1.11) p=0.005]. The LUNDEX was lower in obese vs. non-obese (16% vs. 66% per year, p=0.89, 10.5 vs 74.9% at 2 years, p=0.011 and 5.9 vs 81.8% at 3 years, p=0.005). Conclusions: The average survival of the first DME-b was 6.8 years. The only variable associated with lower survival was the older age.

El recién nacido expuesto a cocaína antenatal: una propuesta de intervención médica y psicosocial integrada / The newborn exposed to antenatal cocaine: a proposal for integrated medical and psychosocial intervention

Introducción: El consumo de cocaína durante la gestación gatilla isquemia, muerte y licuefacción celular en el cerebro fetal, consolidando en la infancia grados variables de retraso mental. El presente estudio busca identificar mediante test de drogas en orina los recién nacidos (RN) expuestos a cocaína en el embarazo y describir el procedimiento clínico y social a seguir. Metodología: Estudio de cohorte prospectivo enero 2016 y enero 2018 en RN con exposición antenatal a cocaína, Unidad de Neonatología del Hospital Clínico San Borja Arriarán. Resultados: Se estudió a 64 RN con test en orina positivo a cocaína. El 42% fue pequeño para la edad gestacional, 33% tenía microcefalia. Se encontraron malformaciones en sistema nervioso y vías urinarias, trastornos del ritmo cardíaco e hipoacusia. Solo 32,8% de las madres controló su embarazo y 52% rechazó la rehabilitación. Servicio Social interpuso medidas de protección a los RN e instó a las madres a programas de rehabilitación. El 12,5% de los RN no tenía familia de apoyo y debió ser derivado a instituciones gubernamentales. Conclusiones: Las consecuencias de la exposición a cocaína antenatal en el RN son devastadoras. Este trabajo permite orientar la pesquisa, estudio y pasos legales a seguir con los RN afectados y sus madres.

Introduction: The consumption of cocaine during pregnancy triggers events such as ischemia, death and cell liquefaction in the fetal brain, consolidating varying degrees of intellectual disability. This study proposed to identify by urine drug test the newborns (NB) with antenatal exposure to and describe the clinical and social procedure to follow with them and their mothers until neonatal discharge. Methodology: Prospective cohort study, conducted in RN who met criteria for risk of antenatal exposure to cocaine, Neonatology Unit of the San Borja Arriaran Clinical Hospital between January 2016 -2018. Results: Antenatal exposure to cocaine was confirmed on 64 NB. Forty-two percent of them were small for gestational age and 33% had microcephaly. Malformations were found in the nervous system urinary tract, as well as disorders in the rhythm of the heart and loss of hearing. Only 32% of mothers controlled her pregnancy, none of them was derived to the secondary. Social Services implemented all the NB protective measures in place and urged mothers to participate in rehabilitation programs. Fifty-two percent rejected rehabilitation and 12.5% of the NB have not family support and had to be referred to government institutions. Conclusions: The consequences of exposure to antenatal cocaine in the NB are devastating. This work allows orienting the research with the NB and showing the legal steps should be taken with the RN and their mothers.