Clinical phenotypes of acute heart failure based on signs and symptoms of perfusion and congestion at emergency department presentation and their relationship with patient management and outcomes

Objective To compare the clinical characteristics and outcomes of patients with acute heart failure (AHF) according to clinical profiles based on congestion and perfusion determined in the emergency department (ED). Methods and results Overall, 11 261 unselected AHF patients from 41 Spanish EDs were classified according to perfusion (normoperfusion = warm; hypoperfusion = cold) and congestion (not = dry; yes = wet). Baseline and decompensation characteristics were recorded as were the main wards to which patients were admitted. The primary outcome was 1-year all-cause mortality; secondary outcomes were need for hospitalisation during the index AHF event, in-hospital all-cause mortality, prolonged hospitalisation, 7-day post-discharge ED revisit for AHF and 30-day post-discharge rehospitalisation for AHF. A total of 8558 patients (76.0%) were warm+ wet, 1929 (17.1%) cold+ wet, 675 (6.0%) warm+ dry, and 99 (0.9%) cold+ dry; hypoperfused (cold) patients were more frequently admitted to intensive care units and geriatrics departments, and warm+ wet patients were discharged home without admission. The four phenotypes differed in most of the baseline and decompensation characteristics. The 1-year mortality was 30.8%, and compared to warm+ dry, the adjusted hazard ratios were significantly increased for cold+ wet (1.660; 95% confidence interval 1.400-1.968) and cold+ dry (1.672; 95% confidence interval 1.189-2.351). Hypoperfused (cold) phenotypes also showed higher rates of index episode hospitalisation and in-hospital mortality, while congestive (wet) phenotypes had a higher risk of prolonged hospitalisation but decreased risk of rehospitalisation. No differences were observed among phenotypes in ED revisit risk. Conclusions Bedside clinical evaluation of congestion and perfusion of AHF patients upon ED arrival and classification according to phenotypic profiles proposed by the latest European Society of Cardiology guidelines provide useful complementary information and help to rapidly predict patient outcomes shortly after ED patient arrival

The Road Traffic Injuries Research Network: a decade of research capacity strengthening in low- and middle-income countries

Road traffic crashes have been an increasing threat to the wellbeing of road users worldwide; an unacceptably high number of people die or become disabled from them. While high-income countries have successfully implemented effective interventions to help reduce the burden of road traffic injuries (RTIs) in their countries, low- and middle-income countries (LMICs) have not yet achieved similar results. Both scientific research and capacity development have proven to be useful for preventing RTIs in high-income countries. In 1999, a group of leading researchers from different countries decided to join efforts to help promote research on RTIs and develop the capacity of professionals from LMICs. This translated into the creation of the Road Traffic Injuries Research Network (RTIRN) – a partnership of over 1,100 road safety professionals from 114 countries collaborating to facilitate reductions in the burden of RTIs in LMICs by identifying and promoting effective, evidenced-based interventions and supporting research capacity building in road safety research in LMICs. This article presents the work that RTIRN has done over more than a decade, including production of a dozen scientific papers, support of nearly 100 researchers, training of nearly 1,000 people and 35 scholarships granted to researchers from LMICs to attend world conferences, as well as lessons learnt and future challenges to maximize its work

Super-enhancer-based identification of a BATF3/IL-2R-module reveals vulnerabilities in anaplastic large cell lymphoma.

Anaplastic large cell lymphoma (ALCL), an aggressive CD30-positive T-cell lymphoma, comprises systemic anaplastic lymphoma kinase (ALK)-positive, and ALK-negative, primary cutaneous and breast implant-associated ALCL. Prognosis of some ALCL subgroups is still unsatisfactory, and already in second line effective treatment options are lacking. To identify genes defining ALCL cell state and dependencies, we here characterize super-enhancer regions by genome-wide H3K27ac ChIP-seq. In addition to known ALCL key regulators, the AP-1-member BATF3 and IL-2 receptor (IL2R)-components are among the top hits. Specific and high-level IL2R expression in ALCL correlates with BATF3 expression. Confirming a regulatory link, IL-2R-expression decreases following BATF3 knockout, and BATF3 is recruited to IL2R regulatory regions. Functionally, IL-2, IL-15 and Neo-2/15, a hyper-stable IL-2/IL-15 mimic, accelerate ALCL growth and activate STAT1, STAT5 and ERK1/2. In line, strong IL-2Rα-expression in ALCL patients is linked to more aggressive clinical presentation. Finally, an IL-2Rα-targeting antibody-drug conjugate efficiently kills ALCL cells in vitro and in vivo. Our results highlight the importance of the BATF3/IL-2R-module for ALCL biology and identify IL-2Rα-targeting as a promising treatment strategy for ALCL

Declínio e desigualdades sociais na mortalidade infantil por diarréia Decline and social inequalities of infant mortality from diarrhea

Este estudo ecológico, temporal e espacial descreve a evolução da mortalidade infantil por doenças infecciosas intestinais (DII) em Salvador, Bahia, no período de 1977 a 1998 e a distribuição dessa mortalidade segundo condições de vida, em 1991. As Zonas de Informação (ZI), da cidade, foram agrupadas segundo um índice de condições de vida (ICV), em quartis. Foram calculados os seguintes indicadores: Mortalidade Infantil Proporcional (MIP), Coeficiente de Mortalidade Infantil (CMI) e Razão de Mortalidade pela referida causa. A análise dos dados foi feita através do cálculo de médias móveis e do teste de qui-quadrado de tendência. Entre 1977 e 1998 o CMI/DII reduziu-se em 91,9%. A razão entre o CMI/DII do estrato de condições de vida "elevadas" para aquele onde as mesmas eram "muito baixas" foi de 1,9 e a MIP foi mais elevada onde eram piores as condições de vida o que requer reorientação das políticas de controle do problema na direção do enfrentamento das causas.<br>This ecological study describes the temporal trend from 1977 to 1998, and spatial patterns of infant mortality from diarrhea in the city of Salvador, Bahia State, Brazil. The annual proportional of infant mortality and specific-cause mortality rate were estimated. Spatial units of geographical zones within the city's urban area were utilized for administrative purposes, which were aggregated according to quartile of living conditions indicators. Over the study period, the diarrhea-induced infant mortality rate decreased 91.9%. The mortality risk from diarrhea in the lowest living condition strata was 90% greater than in the highest conditions. Also, infant mortality due to diarrhea increases proportionally as living conditions worsen, which necessitates a review of the control policies concerning this important public health problem. Although the infant mortality rate declined during the study period, social inequalities related to infant mortality due to diarrhea persist, reflecting a continuing poor social development

The Road Traffic Injuries Research Network: A decade of research capacity strengthening in low- and middle-income countries

Road traffic crashes have been an increasing threat to the wellbeing of road users worldwide; an unacceptably high number of people die or become disabled from them. While high-income countries have successfully implemented effective interventions to help reduce the burden of road traffic injuries (RTIs) in their countries, low- and middle-income countries (LMICs) have not yet achieved similar results. Both scientific research and capacity development have proven to be useful for preventing RTIs in high-income countries. In 1999, a group of leading researchers from different countries decided to join efforts to help promote research on RTIs and develop the capacity of professionals from LMICs. This translated into the creation of the Road Traffic Injuries Research Network (RTIRN) - a partnership of over 1,100 road safety professionals from 114 countries collaborating to facilitate reductions in the burden of RTIs in LMICs by identifying and promoting effective, evidenced-based interventions and supporting research capacity building in road safety research in LMICs. This article presents the work that RTIRN has done over more than a decade, including production of a dozen scientific papers, support of nearly 100 researchers, training of nearly 1,000 people and 35 scholarships granted to researchers from LMICs to attend world conferences, as well as lessons learnt and future challenges to maximize its work