Potilaan ennusteen arviointi ensihoidossa

Väittelijä Jussi Pirneskoski : Helsingin yliopisto, 2021

Ensihoitojärjestelmä Suomessa

Teema : ensihoit

Protein disulfide isomerase activity is essential for viability and extracellular matrix formation in the nematode Caenorhabditis elegans.

Protein disulfide isomerase (PDI) is a multifunctional protein required for many aspects of protein folding and transit through the endoplasmic reticulum. A conserved family of three PDIs have been functionally analysed using genetic mutants of the model organism Caenorhabditis elegans. PDI-1 and PDI-3 are individually nonessential, whereas PDI-2 is required for normal post-embryonic development. In combination, all three genes are synergistically essential for embryonic development in this nematode. Mutations in pdi-2 result in severe body morphology defects, uncoordinated movement, adult sterility, abnormal molting and aberrant collagen deposition. Many of these phenotypes are consistent with a role in collagen biogenesis and extracellular matrix formation. PDI-2 is required for the normal function of prolyl 4-hydroxylase, a key collagen-modifying enzyme. Site-directed mutagenesis indicates that the independent catalytic activity of PDI-2 may also perform an essential developmental function. PDI-2 therefore performs two critical roles during morphogenesis. The role of PDI-2 in collagen biogenesis can be partially restored following complementation of the mutant with human PDI

Ability of prehospital NEWS to predict 1-day and 7-day mortality is reduced in older adult patients

Background National Early Warning Score (NEWS) does not include age as a parameter despite age is a significant independent risk factor of death. The aim of this study was to examine whether age has an effect on predictive performance of short-term mortality of NEWS in a prehospital setting. We also evaluated whether adding age as an additional parameter to NEWS improved its short-term mortality prediction. Methods We calculated NEWS scores from retrospective prehospital electronic patient record data for patients 18 years or older with sufficient prehospital data to calculate NEWS. We used area under receiver operating characteristic (AUROC) to analyse the predictive performance of NEWS for 1 and 7 day mortalities with increasing age in three different age groups: = 80 years. We also explored the ORs for mortality of different NEWS parameters in these age groups. We added age to NEWS as an additional parameter and evaluated its effect on predictive performance. Results We analysed data from 35 800 ambulance calls. Predictive performance for 7-day mortality of NEWS decreased with increasing age: AUROC (95% CI) for 1-day mortality was 0.876 (0.848 to 0.904), 0.824 (0.794 to 0.854) and 0.820 (0.788 to 0.852) for first, second and third age groups, respectively. AUROC for 7-day mortality had a similar trend. Addition of age as an additional parameter to NEWS improved its ability to predict short-term mortality when assessed with continuous Net Reclassification Improvement. Conclusions Age should be considered as an additional parameter to NEWS, as it improved its performance in predicting short-term mortality in this prehospital cohort.Peer reviewe

Intubation first-pass success in a high performing pre-hospital critical care system is not associated with 30-day mortality : a registry study of 4496 intubation attempts

Peer reviewe

Random forest machine learning method outperforms prehospital National Early Warning Score for predicting one-day mortality : A retrospective study

Aim of the study: The National Early Warning Score (NEWS) is a validated method for predicting clinical deterioration in hospital wards, but its performance in prehospital settings remains controversial. Modern machine learning models may outperform traditional statistical analyses for predicting short-term mortality. Thus, we aimed to compare the mortality prediction accuracy of NEWS and random forest machine learning using prehospital vital signs. Methods: In this retrospective study, all electronic ambulance mission reports between 2008 and 2015 in a single EMS system were collected. Adult patients (>= 18 years) were included in the analysis. Random forest models with and without blood glucose were compared to the traditional NEWS for predicting one-day mortality. A ten-fold cross-validation method was applied to train and validate the random forest models. Results: A total of 26,458 patients were included in the study of whom 278 (1.0%) died within one day of ambulance mission. The area under the receiver operating characteristic curve for one-day mortality was 0.836 (95% CI, 0.810-0.860) for NEWS, 0.858 (95% CI, 0.832-0.883) for a random forest trained with NEWS variables only and 0.868 (0.843-0.892) for a random forest trained with NEWS variables and blood glucose. Conclusion: A random forest algorithm trained with NEWS variables was superior to traditional NEWS for predicting one-day mortality in adult prehospital patients, although the risk of selection bias must be acknowledged. The inclusion of blood glucose in the model further improved its predictive performance.Peer reviewe

Urgent EMS managed out-of-hospital delivery dispatches in Helsinki

Background: The aim of this study was to examine Helsinki Emergency Medical Services (EMS) and hospital records to determine the incidence and possible complications of out-of-hospital deliveries managed by EMS in Helsinki. Methods: We retrospectively analysed all urgent ambulance dispatches relating to childbirth in Helsinki from January 1, 2010 to December 31, 2014 with further analysis of hospital records for the out-of-hospital deliveries. Patients were divided in to two groups: those who delivered before reaching hospital and those who did not deliver before reaching hospital and differences between groups were analysed. Deliveries with gestational age of at least 22 + 0 weeks were considered as births in statistical analysis as this is the current national practice. Results: There were 799 urgent dispatches during the study period. In 102 (12.8 %) of these delivery took place before reaching the hospital. The incidence of EMS managed out-of-hospital delivery was found to be 3.0/1000 births. The annual number of out-of-hospital deliveries attended by EMS increased from 15 in 2010 to 28 in 2014. No stillbirths were reported. Neither maternal or perinatal deaths nor major maternal complications were noted in the study population. Discussion: Out-of-hospital deliveries represent a small minority of EMS calls and remain a challenge to maintaining professional capabilities. Small sample size might have limited the ability of the study to pick up rare complications. Conclusions: The amount of out-of-hospital deliveries in Helsinki increased during the five-year study period. There were no maternal or perinatal mortality or major complications resulting in long-term sequelae associated with the EMS-managed out-of-hospital births.Peer reviewe

19F NMR spectroscopy monitors ligand binding to recombinantly fluorine-labelled b'x from human protein disulphide isomerase (hPDI)

We report a protein-observe (19)F NMR-based ligand titration binding study of human PDI b'x with ?-somatostatin that also emphasises the need to optimise recombinant protein fluorination when using 5- or 6-fluoroindole. This study highlights a recombinant preference for 5-fluoroindole over 6-fluoroindole; most likely due to the influence of fluorine atomic packing within the folded protein structure. Fluorination affords a single (19)F resonance probe to follow displacement of the protein x-linker as ligand is titrated and provides a dissociation constant of 23 ± 4 ?M

Prolyl 4-hydroxlase activity is essential for development and cuticle formation in the human infective parasitic nematode Brugia malayi

Collagen prolyl 4-hydroxylases (C-P4H) are required for formation of extracellular matrices in higher eukaryotes. These enzymes convert proline residues within the repeat regions of collagen polypeptides to 4-hydroxyproline, a modification essential for the stability of the triple helix. C-P4Hs are most often oligomeric complexes, with enzymatic activity contributed by the α subunits, and the β subunits formed by protein disulfide isomerase (PDI). Here we characterise this enzyme class in the important human parasitic nematode Brugia malayi. All potential C-P4H subunits were identified by detailed bioinformatic analysis of sequence databases, function was investigated both by RNAi in the parasite and heterologous expression in Caenorhabditis elegans, while biochemical activity and complex formation were examined via co-expression in insect cells. Simultaneous RNAi of two B. malayi C-P4H α subunit-like genes resulted in a striking, highly penetrant body morphology phenotype in parasite larvae. This was replicated by single RNAi of a B. malayi C-P4H β subunit-like PDI. Surprisingly however, the B. malayi proteins were not capable of rescuing a C. elegans α subunit mutant, whereas the human enzymes could. In contrast, the B. malayi PDI did functionally complement the lethal phenotype of a C. elegans β subunit mutant. Comparison of recombinant and parasite derived material indicates that enzymatic activity may be dependent on a non-reducible, inter-subunit cross-link, present only in the parasite. We therefore demonstrate that C-P4H activity is essential for development of B. malayi and uncover a novel parasite-specific feature of these collagen biosynthetic enzymes that may be exploited in future parasite control

Intubation first-pass success in a high performing pre-hospital critical care system is not associated with 30-day mortality: a registry study of 4496 intubation attempts

BackgroundLower intubation first-pass success (FPS) rate is associated with physiological deterioration, and FPS is widely used as a quality indicator of the airway management of a critically ill patient. However, data on FPS's association with survival is limited. We aimed to investigate if the FPS rate is associated with 30-day mortality or physiological complications in a pre-hospital setting. Furthermore, we wanted to describe the FPS rate in Finnish helicopter emergency medical services. MethodsThis was a retrospective observational study. Data on drug-facilitated intubation attempts by helicopter emergency medical services were gathered from a national database and analysed. Multivariate logistic regression, including known prognostic factors, was performed to assess the association between FPS and 30-day mortality, collected from population registry data. ResultsOf 4496 intubation attempts, 4082 (91%) succeeded on the first attempt. The mortality rates in FPS and non-FPS patients were 34% and 38% (P = 0.21), respectively. The adjusted odds ratio of FPS for 30-day mortality was 0.88 (95% CI 0.66-1.16). Hypoxia after intubation and at the time of handover was more frequent in the non-FPS group (12% vs. 5%, P ConclusionFPS is not associated with 30-day mortality in pre-hospital critical care delivered by advanced providers. It should therefore be seen more as a process quality indicator instead of a risk factor of poor outcome, at least considering the current limitations of the parameter.</p