Outcome prediction for hypothermic patients in cardiac arrest.

The 5A score predicts in-hospital mortality of patients suffering from accidental hypothermia, including those not in cardiac arrest. The HOPE score was specifically developed to predict survival for the subgroup of hypothermic patients in cardiac considered for extracorporeal life support rewarming. The C-statistic in the external validation study of the HOPE score was 0.825 (95% CI: 0.753-0.897), confirming its excellent discrimination. In addition, its good calibration allows for a reliable interpretation of the corresponding survival probability after rewarming. The HOPE score should be used for predicting outcome and selecting hypothermic patients in cardiac arrest for rewarming

Clinician miscalibration of survival estimate in hypothermic cardiac arrest: HOPE-estimated survival probabilities in extreme cases.

Patients with hypothermic cardiac arrest may survive with an excellent outcome after extracorporeal life support rewarming (ECLSR). The HOPE (Hypothermia Outcome Prediction after ECLS) score is recommended to guide the in-hospital decision on whether or not to initiate ECLSR in patients in cardiac arrest following accidental hypothermia. We aimed to assess the HOPE-estimated survival probabilities for a set of survivors of hypothermic cardiac arrest who had extreme values for the variables included in the HOPE score. Survivors were identified and selected through a systematic literature review including case reports. We calculated the HOPE score for each patient who presented extraordinary clinical parameters. We identified 12 such survivors. The HOPE-estimated survival probability was ≥10% for all (n = 11) patients for whom we were able to calculate the HOPE score. Our study confirms the robustness of the HOPE score for outliers and thus further confirms its external validity. These cases also confirm that hypothermic cardiac arrest is a fundamentally different entity than normothermic cardiac arrest. Using HOPE for extreme cases may support the proper calibration of a clinician's prognosis and therapeutic decision based on the survival chances of patients with accidental hypothermic cardiac arrest

The Efficacy of Renal Replacement Therapy for Rewarming of Patients in Severe Accidental Hypothermia-Systematic Review of the Literature.

Renal replacement therapy (RRT) can be used to rewarm patients in deep hypothermia. However, there is still no clear evidence for the effectiveness of RRT in this group of patients. This systematic review aims to summarize the rewarming rates during RRT in patients in severe hypothermia, below or equal to 32 °C. This systematic review was registered in the PROSPERO International Prospective Register of Systematic Reviews (identifier CRD42021232821). We searched Embase, Medline, and Cochrane databases using the keywords hypothermia, renal replacement therapy, hemodialysis, hemofiltration, hemodiafiltration, and their abbreviations. The search included only articles in English with no time limit, up until 30 June 2021. From the 795 revised articles, 18 studies including 21 patients, were selected for the final assessment and data extraction. The mean rate of rewarming calculated for all studies combined was 1.9 °C/h (95% CI 1.5-2.3) and did not differ between continuous (2.0 °C/h; 95% CI 0.9-3.0) and intermittent (1.9 °C/h; 95% CI 1.5-2.3) methods (p > 0.9). Based on the reviewed literature, it is currently not possible to provide high-quality recommendations for RRT use in specific groups of patients in accidental hypothermia. While RRT appears to be a viable rewarming strategy, the choice of rewarming method should always be determined by the specific clinical circumstances, the available resources, and the current resuscitation guidelines

Prognosis of Hypothermic Patients Undergoing ECLS Rewarming-Do Alterations in Biochemical Parameters Matter?

While ECLS is a highly invasive procedure, the identification of patients with a potentially good prognosis is of high importance. The aim of this study was to analyse changes in the acid-base balance parameters and lactate kinetics during the early stages of ECLS rewarming to determine predictors of clinical outcome. This single-centre retrospective study was conducted at the Severe Hypothermia Treatment Centre at John Paul II Hospital in Krakow, Poland. Patients ≥18 years old who had a core temperature (Tc) < 30 °C and were rewarmed with ECLS between December 2013 and August 2018 were included. Acid-base balance parameters were measured at ECLS implantation, at Tc 30 °C, and at 2 and 4 h after Tc 30 °C. The alteration in blood lactate kinetics was calculated as the percent change in serum lactate concentration relative to the baseline. We included 50 patients, of which 36 (72%) were in cardiac arrest. The mean age was 56 ± 15 years old, and the mean Tc was 24.5 ± 12.6 °C. Twenty-one patients (42%) died. Lactate concentrations in the survivors group were significantly lower than in the non-survivors at all time points. In the survivors group, the mean lactate concentration decreased -2.42 ± 4.49 mmol/L from time of ECLS implantation until 4 h after reaching Tc 30 °C, while in the non-survivors' group (p = 0.024), it increased 1.44 ± 6.41 mmol/L. Our results indicate that high lactate concentration is associated with a poor prognosis for hypothermic patients undergoing ECLS rewarming. A decreased value of lactate kinetics at 4 h after reaching 30 °C is also associated with a poor prognosis

Data and methods to calculate cut-off values for serum potassium and core temperature at hospital admission for extracorporeal rewarming of avalanche victims in cardiac arrest.

The data and estimation methods presented in this article are associated with the research article, "Cut-off values of serum potassium and core temperature at hospital admission for extracorporeal rewarming of avalanche victims in cardiac arrest: a retrospective multi-centre study" [1]. In this article we estimate recommended cut-off values for in-hospital triage with respect to extracorporeal rewarming. With only 6 survivors of 103 patients collected over a period of 20 years the ability to estimate reliable threshold values is limited. In addition, because the number of avalanche victims is also limited, a significantly larger dataset is unlikely to be obtained. We have therefore adapted two non-parametric estimation methods (bootstrapping and exact binomial distribution) to our specific needs and performed a simulations to confirm validity and reliability

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Analysis of expressed sequence tags from Trypanosoma cruzi amastigotes

A total of 880 expressed sequence tags (EST) originated from clones randomly selected from a Trypanosoma cruzi amastigote cDNA library have been analyzed. Of these, 40% (355 ESTs) have been identified by similarity to sequences in public databases and classified according to functional categorization of their putative products. About 11% of the mRNAs expressed in amastigotes are related to the translational machinery, and a large number of them (9% of the total number of clones in the library) encode ribosomal proteins. A comparative analysis with a previous study, where clones from the same library were selected using sera from patients with Chagas disease, revealed that ribosomal proteins also represent the largest class of antigen coding genes expressed in amastigotes (54% of all immunoselected clones). However, although more than thirty classes of ribosomal proteins were identified by EST analysis, the results of the immunoscreening indicated that only a particular subset of them contains major antigenic determinants recognized by antibodies from Chagas disease patients

Nucleolar Accumulation of RNA Binding Proteins Induced by ActinomycinD Is Functional in Trypanosoma cruzi and Leishmania mexicana but Not in T. brucei

We have recently shown in T. cruzi that a group of RNA Binding Proteins (RBPs), involved in mRNA metabolism, are accumulated into the nucleolus in response to Actinomycin D (ActD) treatment. In this work, we have extended our analysis to other members of the trypanosomatid lineage. In agreement with our previous study, the mechanism seems to be conserved in L. mexicana, since both endogenous RBPs and a transgenic RBP were relocalized to the nucleolus in parasites exposed to ActD. In contrast, in T. brucei, neither endogenous RBPs (TbRRM1 and TbPABP2) nor a transgenic RBP from T. cruzi were accumulated into the nucleolus under such treatment. Interestingly, when a transgenic TbRRM1was expressed in T. cruzi and the parasites exposed to ActD, TbRRM1 relocated to the nucleolus, suggesting that it contains the necessary sequence elements to be targeted to the nucleolus. Together, both experiments demonstrate that the mechanism behind nucleolar localization of RBPs, which is present in T. cruzi and L. mexicana, is not functional in T. brucei, suggesting that it has been lost or retained differentially during the evolution of the trypanosomatid lineage

Comparative Genomics Reveals Two Novel RNAi Factors in Trypanosoma brucei and Provides Insight into the Core Machinery

The introduction ten years ago of RNA interference (RNAi) as a tool for molecular exploration in Trypanosoma brucei has led to a surge in our understanding of the pathogenesis and biology of this human parasite. In particular, a genome-wide RNAi screen has recently been combined with next-generation Illumina sequencing to expose catalogues of genes associated with loss of fitness in distinct developmental stages. At present, this technology is restricted to RNAi-positive protozoan parasites, which excludes T. cruzi, Leishmania major, and Plasmodium falciparum. Therefore, elucidating the mechanism of RNAi and identifying the essential components of the pathway is fundamental for improving RNAi efficiency in T. brucei and for transferring the RNAi tool to RNAi-deficient pathogens. Here we used comparative genomics of RNAi-positive and -negative trypanosomatid protozoans to identify the repertoire of factors in T. brucei. In addition to the previously characterized Argonaute 1 (AGO1) protein and the cytoplasmic and nuclear Dicers, TbDCL1 and TbDCL2, respectively, we identified the RNA Interference Factors 4 and 5 (TbRIF4 and TbRIF5). TbRIF4 is a 3′-5′ exonuclease of the DnaQ superfamily and plays a critical role in the conversion of duplex siRNAs to the single-stranded form, thus generating a TbAGO1-siRNA complex required for target-specific cleavage. TbRIF5 is essential for cytoplasmic RNAi and appears to act as a TbDCL1 cofactor. The availability of the core RNAi machinery in T. brucei provides a platform to gain mechanistic insights in this ancient eukaryote and to identify the minimal set of components required to reconstitute RNAi in RNAi-deficient parasites