Efectos renales adversos por inhibidores del check-point (ICP) en pacientes con cáncer. Recomendaciones del grupo de Onconefrología de la Sociedad Española de Nefrología (SEN)

Insuficiència renal aguda; ImmunoteràpiaAcute kidney injury; ImmunotherapyInsuficiencia renal aguda; InmunoterapiaThe most widely used approach in the immunotherapy treatment of cancer is the administration of monoclonal antibodies directed against regulatory molecules of immune control that inhibit the activation of T cells, the so-called check point inhibitors (ICI). ICI nephrotoxicity epidemiology and pathology; its diagnosis with or without kidney biopsy; the type and duration of treatment; the possibility of rechallenging after kidney damage; and its indication in patients with cancer and renal transplantation are certainly controversial. In the absence of definitive studies, this document is intended to specify some recommendations agreed by the group of Onconephrology experts of the Spanish Society of Nephrology in those areas related to ICI nephrotoxicity, in order to help decision-making in daily clinical practice in Onconephrology consultations.El enfoque más utilizado en el tratamiento inmunoterápico del cáncer es la administración de anticuerpos monoclonales dirigidos contra moléculas reguladoras del control inmunitario que inhiben la activación de las células T, los llamados inhibidores del Check-Point (ICP). La epidemiología y patología de la nefrotoxicidad por los ICP; su diagnóstico con o sin biopsia renal; el tipo y la duración del tratamiento; la posibilidad de retratar después del daño renal; y su indicación en pacientes con cáncer y trasplante renal son ciertamente controvertidas. En ausencia de estudios definitivos, este documento está destinado a concretar unas recomendaciones consensuadas por el grupo de expertos de Onconefrología de la S.E.N en aquellas áreas relacionadas con la nefrotoxicidad por los ICP, con la finalidad de ayudar en la toma de decisiones en la práctica clínica diaria de las consultas de Onconefrología

Why do physicians prescribe dialysis? A prospective questionnaire study

IntroductionThe incidence of unplanned dialysis initiation (DI) with consequent increased comorbidity, mortality and reduced modality choice remains high, but the optimal timing of dialysis initiation (DI) remains controversial, and there is a lack of studies of specific reasons for DI. We investigated why and when physicians prescribe dialysis and hypothesized that physician motivation for DI is an independent factor which may have clinical consequences.MethodsIn the Peridialysis study, an ongoing multicenter prospective study assessing the causes and timing of DI and consequences of unplanned dialysis, physicians in 11 hospitals were asked to describe their primary, secondary and further reasons for prescribing DI. The stated reasons for DI were analyzed in relation to clinical and biochemical data at DI, and characteristics of physicians.ResultsIn 446 patients (median age 67 years; 38% females; diabetes 25.6%), DI was prescribed by 84 doctors who stated 23 different primary reasons for DI. The primary indication was clinical in 63% and biochemical in 37%; 23% started for life-threatening conditions. Reduced renal function accounted for only 19% of primary reasons for DI but was a primary or contributing reason in 69%. The eGFR at DI was 7.2 ±3.4 ml/min/1.73 m2, but varied according to comorbidity and cause of DI. Patients with cachexia, anorexia and pulmonary stasis (34% with heart failure) had the highest eGFR (8.2–9.8 ml/min/1.73 m2), and those with edema, “low GFR”, and acidosis, the lowest (4.6–6.1 ml/min/1.73 m2). Patients with multiple comorbidity including diabetes started at a high eGFR (8.7 ml/min/1.73 m2). Physician experience played a role in dialysis prescription. Non-specialists were more likely to prescribe dialysis for life-threatening conditions, while older and more experienced physicians were more likely to start dialysis for clinical reasons, and at a lower eGFR. Female doctors started dialysis at a higher eGFR than males (8.0 vs. 7.1 ml/min/1.73 m2).ConclusionsDI was prescribed mainly based on clinical reasons in accordance with current recommendations while low renal function accounted for only 19% of primary reasons for DI. There are considerable differences in physicians´ stated motivations for DI, related to their age, clinical experience and interpretation of biochemical variables. These differences may be an independent factor in the clinical treatment of patients, with consequences for the risk of unplanned DI.</div

Why do physicians prescribe dialysis? A prospective questionnaire study

Funding Information: This study was supported by an unrestricted grant 14CECPDEU1001 from Baxter Healthcare International. Baxter Novum is the result of a grant from Baxter Healthcare Corporation to Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, to support research activities at Karolinska Institutet to promote the understanding and treatment of renal disease. Bengt Lindholm is employed by Baxter Healthcare Corporation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Publisher Copyright: © 2017 Heaf et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright: Copyright 2018 Elsevier B.V., All rights reserved.Introduction.The incidence of unplanned dialysis initiation (DI) with consequent increased comorbidity, mortality and reduced modality choice remains high, but the optimal timing of dialysis initiation (DI) remains controversial, and there is a lack of studies of specific reasons for DI. We investigated why and when physicians prescribe dialysis and hypothesized that physician motivation for DI is an independent factor which may have clinical consequences. Methods In the Peridialysis study, an ongoing multicenter prospective study assessing the causes and timing of DI and consequences of unplanned dialysis, physicians in 11 hospitals were asked to describe their primary, secondary and further reasons for prescribing DI. The stated reasons for DI were analyzed in relation to clinical and biochemical data at DI, and characteristics of physicians. Results In 446 patients (median age 67 years; 38% females; diabetes 25.6%), DI was prescribed by 84 doctors who stated 23 different primary reasons for DI. The primary indication was clinical in 63% and biochemical in 37%; 23% started for life-threatening conditions. Reduced renal function accounted for only 19% of primary reasons for DI but was a primary or contributing reason in 69%. The eGFR at DI was 7.2 ±3.4 ml/min/1.73 m2, but varied according to comorbidity and cause of DI. Patients with cachexia, anorexia and pulmonary stasis (34% with heart failure) had the highest eGFR (8.2–9.8 ml/min/1.73 m2), and those with edema, “low GFR”, and acidosis, the lowest (4.6–6.1 ml/min/1.73 m2). Patients with multiple comorbidity including diabetes started at a high eGFR (8.7 ml/min/1.73 m2). Physician experience played a role in dialysis prescription. Non-specialists were more likely to prescribe dialysis for life-threatening conditions, while older and more experienced physicians were more likely to start dialysis for clinical reasons, and at a lower eGFR. Female doctors started dialysis at a higher eGFR than males (8.0 vs. 7.1 ml/min/1.73 m2). Conclusions DI was prescribed mainly based on clinical reasons in accordance with current recommendations while low renal function accounted for only 19% of primary reasons for DI. There are considerable differences in physicians´ stated motivations for DI, related to their age, clinical experience and interpretation of biochemical variables. These differences may be an independent factor in the clinical treatment of patients, with consequences for the risk of unplanned DI.publishersversionPeer reviewe

TORTURA Y PROTOCOLO DE ESTABMBÚL: Perspectivas, alternativas y contextos

La obra presenta el tema central de la tortura que esta presente en la sociedad mexicana. Sus perspectivas, alternativas y contextos.El libro consta de 23 capítulos en los cuales los autores presentan de forma analítica y crítica el contexto de la tortura en México; sus efectos, alcances y perspectivas

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017

Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2\ub75th percentile and 100 as the 97\ub75th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59\ub74 (IQR 35\ub74–67\ub73), ranging from a low of 11\ub76 (95% uncertainty interval 9\ub76–14\ub70) to a high of 84\ub79 (83\ub71–86\ub77). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030

Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of 'leaving no one behind', it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990-2017, projected indicators to 2030, and analysed global attainment. METHODS: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0-100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator