Redefining palliative care-a new consensus-based definition

Context: The International Association for Hospice and Palliative Care developed a consensus-based definition of palliative care (PC) that focuses on the relief of serious health-related suffering, a concept put forward by the Lancet Commission Global Access to Palliative Care and Pain Relief. Objective: The main objective of this article is to present the research behind the new definition. Methods: The three-phased consensus process involved health care workers from countries in all income levels. In Phase 1, 38 PC experts evaluated the components of the World Health Organization definition and suggested new/revised ones. In Phase 2, 412 International Association for Hospice and Palliative Care members in 88 countries expressed their level of agreement with the suggested components. In Phase 3, using results from Phase 2, the expert panel developed the definition. Results: The consensus-based definition is as follows: Palliative care is the active holistic care of individuals across all ages with serious health-related suffering due to severe illness and especially of those near the end of life. It aims to improve the quality of life of patients, their families and their caregivers. The definition includes a number of bullet points with additional details as well as recommendations for governments to reduce barriers to PC. Conclusion: Participants had significantly different perceptions and interpretations of PC. The greatest challenge faced by the core group was trying to find a middle ground between those who think that PC is the relief of all suffering and those who believe that PC describes the care of those with a very limited remaining life span

Endophyte Microbiome Diversity in Micropropagated Atriplex canescens and Atriplex torreyi var griffithsii

Microbial diversity associated with micropropagated Atriplex species was assessed using microscopy, isolate culturing, and sequencing. Light, electron, and confocal microscopy revealed microbial cells in aseptically regenerated leaves and roots. Clone libraries and tag-encoded FLX amplicon pyrosequencing (TEFAP) analysis amplified sequences from callus homologous to diverse fungal and bacterial taxa. Culturing isolated some seed borne endophyte taxa which could be readily propagated apart from the host. Microbial cells were observed within biofilm-like residues associated with plant cell surfaces and intercellular spaces. Various universal primers amplified both plant and microbial sequences, with different primers revealing different patterns of fungal diversity. Bacterial and fungal TEFAP followed by alignment with sequences from curated databases revealed 7 bacterial and 17 ascomycete taxa in A. canescens, and 5 bacterial taxa in A. torreyi. Additional diversity was observed among isolates and clone libraries. Micropropagated Atriplex retains a complex, intimately associated microbiome which includes diverse strains well poised to interact in manners that influence host physiology. Microbiome analysis was facilitated by high throughput sequencing methods, but primer biases continue to limit recovery of diverse sequences from even moderately complex communities

2019 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations

The International Liaison Committee on Resuscitation has initiated a continuous review of new, peer-reviewed, published cardiopulmonary resuscitation science. This is the third annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. It addresses the most recent published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. This summary addresses the role of cardiac arrest centers and dispatcher-assisted cardiopulmonary resuscitation, the role of extracorporeal cardiopulmonary resuscitation in adults and children, vasopressors in adults, advanced airway interventions in adults and children, targeted temperature management in children after cardiac arrest, initial oxygen concentration during resuscitation of newborns, and interventions for presyncope by first aid providers. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the certainty of the evidence on the basis of the Grading of Recommendations, Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence to Decision Framework Highlights sections. The task forces also listed priority knowledge gaps for further research

The contribution of X-linked coding variation to severe developmental disorders

Abstract: Over 130 X-linked genes have been robustly associated with developmental disorders, and X-linked causes have been hypothesised to underlie the higher developmental disorder rates in males. Here, we evaluate the burden of X-linked coding variation in 11,044 developmental disorder patients, and find a similar rate of X-linked causes in males and females (6.0% and 6.9%, respectively), indicating that such variants do not account for the 1.4-fold male bias. We develop an improved strategy to detect X-linked developmental disorders and identify 23 significant genes, all of which were previously known, consistent with our inference that the vast majority of the X-linked burden is in known developmental disorder-associated genes. Importantly, we estimate that, in male probands, only 13% of inherited rare missense variants in known developmental disorder-associated genes are likely to be pathogenic. Our results demonstrate that statistical analysis of large datasets can refine our understanding of modes of inheritance for individual X-linked disorders

In Utero Activation of Natural Killer Cells in Congenital Cytomegalovirus Infection.

BackgroundCongenital cytomegalovirus (CMV) infection is the most common infectious cause of birth defects and neurological damage in newborns. Despite a well-established role for natural killer (NK) cells in control of CMV infection in older children and adults, it remains unknown whether fetal NK cells can sense and respond to CMV infection acquired in utero.MethodsHere, we investigate the impact of congenital CMV infection on the neonatal NK-cell repertoire by assessing the frequency, phenotype, and functional profile of NK cells in cord blood samples from newborns with congenital CMV and from uninfected controls enrolled in a birth cohort of Ugandan mothers and infants.ResultsWe find that neonatal NK cells from congenitally CMV infected newborns show increased expression of cytotoxic mediators, signs of maturation and activation, and an expansion of mature CD56- NK cells, an NK-cell subset associated with chronic viral infections in adults. Activation was particularly prominent in NK cell subsets expressing the Fcγ receptor CD16, indicating a role for antibody-mediated immunity against CMV in utero.ConclusionsThese findings demonstrate that NK cells can be activated in utero and suggest that NK cells may be an important component of the fetal and infant immune response against CMV.Clinical trials registrationNCT02793622

Association of Inhibitory Killer Cell Immunoglobulin-like Receptor Ligands With Higher Plasmodium falciparum Parasite Prevalence.

Killer cell immunoglobulin-like receptors (KIRs) and their HLA ligands influence the outcome of many infectious diseases. We analyzed the relationship of compound KIR-HLA genotypes with risk of Plasmodium falciparum infection in a longitudinal cohort of 890 Ugandan individuals. We found that presence of HLA-C2 and HLA-Bw4, ligands for inhibitory KIR2DL1 and KIR3DL1, respectively, increased the likelihood of P. falciparum parasitemia in an additive manner. Individuals homozygous for HLA-C2, which mediates strong inhibition via KIR2DL1, had the highest odds of parasitemia, HLA-C1/C2 heterozygotes had intermediate odds, and individuals homozygous for HLA-C1, which mediates weaker inhibition through KIR2DL2/3, had the lowest odds of parasitemia. In addition, higher surface expression of HLA-C, the ligand for inhibitory KIR2DL1/2/3, was associated with a higher likelihood of parasitemia. Together these data indicate that stronger KIR-mediated inhibition confers a higher risk of P. falciparum parasitemia and suggest that KIR-expressing effector cells play a role in mediating antiparasite immunity

Continuous neuromuscular blockade is associated with decreased mortality in post-cardiac arrest patients

a b s t r a c t Aim: Neuromuscular blockade may improve outcomes in patients with acute respiratory distress syndrome. In post-cardiac arrest patients receiving therapeutic hypothermia, neuromuscular blockade is often used to prevent shivering. Our objective was to determine whether neuromuscular blockade is associated with improved outcomes after out-of-hospital cardiac arrest. Methods: A post hoc analysis of a prospective observational study of comatose adult (>18 years) outof-hospital cardiac arrest at 4 tertiary cardiac arrest centers. The primary exposure of interest was neuromuscular blockade for 24 h following return of spontaneous circulation and primary outcomes were in-hospital survival and functional status at hospital discharge. Secondary outcomes were evolution of oxygenation (PaO 2 :FiO 2 ), and change in lactate. We tested the primary outcomes of in-hospital survival and neurologically intact survival with multivariable logistic regression. Secondary outcomes were tested with multivariable linear mixed-models. Results: A total of 111 patients were analyzed. In patients with 24 h of sustained neuromuscular blockade, the crude survival rate was 14/18 (78%) compared to 38/93 (41%) in patients without sustained neuromuscular blockade (p = 0.004). After multivariable adjustment, neuromuscular blockade was associated with survival (adjusted OR: 7.23, 95% CI: 1.56-33.38). There was a trend toward improved functional outcome with neuromuscular blockade (50% versus 28%; p = 0.07). Sustained neuromuscular blockade was associated with improved lactate clearance (adjusted p = 0.01). Conclusions: We found that early neuromuscular blockade for a 24-h period is associated with an increased probability of survival. Secondarily, we found that early, sustained neuromuscular blockade is associated with improved lactate clearance