Prehospital triage of acute aortic syndrome using a machine learning algorithm.

BACKGROUND: Acute aortic syndrome (AAS) comprises a complex and potentially fatal group of conditions requiring emergency specialist management. The aim of this study was to build a prediction algorithm to assist prehospital triage of AAS. METHODS: Details of consecutive patients enrolled in a regional specialist aortic network were collected prospectively. Two prediction algorithms for AAS based on logistic regression and an ensemble machine learning method called SuperLearner (SL) were developed. Undertriage was defined as the proportion of patients with AAS not transported to the specialist aortic centre, and overtriage as the proportion of patients with alternative diagnoses but transported to the specialist aortic centre. RESULTS: Data for 976 hospital admissions between February 2010 and June 2017 were included; 609 (62·4 per cent) had AAS. Overtriage and undertriage rates were 52·3 and 16·1 per cent respectively. The population was divided into a training cohort (743 patients) and a validation cohort (233). The area under the receiver operating characteristic (ROC) curve values for the logistic regression score and the SL were 0·68 (95 per cent c.i. 0·64 to 0·72) and 0·87 (0·84 to 0·89) respectively (P < 0·001) in the training cohort, and 0·67 (0·60 to 0·74) and 0·73 (0·66 to 0·79) in the validation cohort (P = 0·038). The logistic regression score was associated with undertriage and overtriage rates of 33·7 (bootstrapped 95 per cent c.i. 29·3 to 38·3) and 7·2 (4·8 to 9·8) per cent respectively, whereas the SL yielded undertriage and overtriage rates of 1·0 (0·3 to 2·0) and 30·2 (25·8 to 34·8) per cent respectively. CONCLUSION: A machine learning prediction model performed well in discriminating AAS and could be clinically useful in prehospital triage of patients with suspected AAS.

ANTECEDENTES: Los síndromes aórticos agudos (aortic acute syndromes, AAS) constituyen un grupo complejo y potencialmente letal de entidades que requieren un tratamiento especializado en emergencias. El objetivo de este estudio fue construir un algoritmo de predicción para ayudar a la selección prehospitalaria de los AAS. MÉTODOS: Se recogieron prospectivamente una serie de pacientes consecutivos inscritos en una red regional especializada en patología aórtica. Se desarrollaron dos algoritmos de predicción para AAS basados en una regresión logística y en un método de aprendizaje automático denominado Super Learner (SL). Undertriage (infra-selección) se definió como la proporción de pacientes con AAS no transportados al centro especializado en patología aórtica y el overtriage (sobre-selección) como la proporción de pacientes con diagnósticos alternativos al AAS pero transportados al centro especializado en patología aórtica. RESULTADOS: Se incluyeron los datos de 976 ingresos hospitalarios entre febrero de 2010 y junio de 2017, con 609 (62,4%) AAS. Las tasas de overtriage y undertriage fueron del 52,3% y del 16,1%, respectivamente. La población se dividió en una cohorte de entrenamiento (n = 743) y en una cohorte de validación (n = 233). El área bajo la curva ROC para la puntuación de regresión logística y el SL fueron de 0,68 (0,64, 0,72) y de 0,87 (0,84, 0,89), respectivamente (P < 0,001) en la cohorte de entrenamiento, y de 0,67 (0,60, 0,74) y de 0,73 (0,66, 0,79) en la cohorte de validación (P = 0,038). La puntuación de regresión logística se asoció con tasas de undertriage y overtriage de 33,7% (i.c. del 95% bootstrapped 29,3%, 38,3%) y de 7,2% (4,8%, 9,8%), respectivamente, mientras que el SL presentó tasas de undertriage y overtriage de 1,0% (0,3%, 2,0%) y de 30,2% (25,8%, 34,8%), respectivamente. CONCLUSIÓN: El modelo de predicción de aprendizaje automático funcionó bien para discriminar AAS y podría ser clínicamente útil en la selección prehospitalaria de pacientes con sospecha de síndrome aórtico agudo.

Determination of optimal timing of serial in-utero transfusions in red-cell alloimmunization.

OBJECTIVES: To assess the performance of middle cerebral artery peak systolic velocity (MCA-PSV) and of the expected daily decrease in fetal hemoglobin in determining the timing of serial in-utero transfusions (IUT) in red-cell alloimmunization. METHODS: This was a retrospective study of a continuous series of suspected anemic fetuses undergoing IUT between June 2003 and December 2012. Doppler measurement of MCA-PSV and pre- and post-transfusion hemoglobin levels were recorded at the time of the first, second and third IUT. Receiver-operating characteristics (ROC) curves and negative and positive predictive values of MCA-PSV in the prediction of severe fetal anemia were calculated. The daily decrease of fetal hemoglobin (Hb) between IUTs was calculated. Regression analysis was used to assess the correlation between pretransfusion fetal hemoglobin and MCA-PSV, and between observed and expected (by projection of daily decreases) pretransfusion fetal hemoglobin levels. RESULTS: One hundred and eleven fetuses required an IUT, of which 96 and 67 received a second and third IUT, respectively. The area under the ROC curve for MCA-PSV in the prediction of severe fetal anemia was not different for each rank of transfusion. The positive predictive value of MCA-PSV decreased from 75.3% at the first IUT, to 46.7% and 48.8% at the second and third IUTs, respectively, while the negative predictive value for a 1.5-MoM threshold remained high (88.9% at the second and 91.7% at the third IUT). The mean daily decrease in hemoglobin following each transfusion was 0.45, 0.35 and 0.32 g/dL, respectively. There was a persistent linear correlation between fetal hemoglobin and MCA-PSV and between observed and expected fetal hemoglobin levels. CONCLUSIONS: Both MCA-PSV and projection of daily decrease in hemoglobin are reliable means of diagnosing fetal anemia following previous IUTs. The high negative predictive value of MCA-PSV could allow subsequent IUTs to be postponed in selected cases.

Anticancer drugs induce necrosis of human endothelial cells involving both oncosis and apoptosis.

The endothelium is the first physiological barrier between blood and tissues and can be injured by physical or chemical stress, particularly by the drugs used in cancer therapy. We found that four anticancer agents: etoposide, doxorubicin, bleomycin and paclitaxel induced apoptosis in human umbilical vein endothelial cells (HUVECs) (as judged by DNA fragmentation) with a time- and concentration-dependent decrease in bcl-2 protein but without the involvement of p53. As revealed by immunoblotting, bax protein was expressed in HUVECs treated with 1 mg/ml etoposide whereas bcl-2 protein disappeared. Oncosis occurred parallel to apoptosis with the release of lactate dehydrogenase into the supernatant, and, for doxorubicin and etoposide with the inversion of the distribution of angiotensin I-converting enzyme between supernatant and cells. Among the four tested anticancer drugs, only doxorubicin induced an oxidative stress, with significative malondialdehyde production. Thus, human endothelial cells in confluent cultures seem to be in an equilibrium of resistance to apoptosis related to bcl-2 expression; this equilibrium can be disrupted by a chemical stress, such as the antiproliferative drugs known as pro-apoptotic for tumour cells. For doxorubicin and bleomycin, this cellular toxicity can be related to their unwanted effects in human cancer therapy. Low doses of doxorubicin, paclitaxel or etoposide, however, could induce apoptosis of endothelial cells of new vessels surrounding the tumour, thus leading to specific vessel regression with minimal toxic effects for the endothelium of the other vessels. These findings provide evidence of relationships between endothelial toxicity of anticancer drugs and the key role of bcl-2 for resistance of endothelium cells toward apoptosis; moreover lack of p53 and bax in quiescent cells contributes to resistance of endothelial cells to DNA-damaging agents.

Body temperature and locomotor activity as marker rhythms of aging of the circadian system in rodents.

Most biological functions present rhythmic variations. These rhythms are distinguished by their period and concern all the levels of biological life. Circadian rhythms follow a periodicity close to 24-h, they allow individuals to survive via adaptation to the periodic variations of environment. Throughout the aging process, modifications in circadian rhythms of endocrinological, metabolical and behavioural fields have been found in many animal species. This review updates the body of knowledge on aging-related alterations of the circadian rhythms of body temperature and locomotor activity: modifications in circadian profiles, modifications in the period of free-running rhythms, internal desynchronisations and modifications in entrainment ability of these rhythms.

Circadian rhythms of body temperature and motor activity in rodents their relationships with the light-dark cycle.

In rodents, the alternation of light and dark is the main synchronizer of circadian rhythms. The entrainment abilities of the LD cycle could be estimated by experimental modifications of the photoperiod and by following the subsequent temporal distribution of a circadian rhythm. The rate of reentrainment of a rhythm is determined by the nature of the studied variable, by the direction (advance or delay) and the magnitude (or value) of the phase shift. In rodents, core body temperature and motor activity are known to be well synchronized with each other under L:D 12:12 and under constant conditions (LL or DD). There are clear evidences that the circadian pattern of motor activity is generated by two oscillators, one from dusk signal and the other from dawn signal. Whether the circadian rhythms of body temperature and motor activity are generated by a common circadian mechanism or controlled by separate ones still remains unknown. The purpose of this review is to summarize the results obtained on the circadian rhythms of body temperature and motor activity throughout the daily cycle in order to clarify the relationships between these two functions.

Naive T-cells in myelodysplastic syndrome display intrinsic human telomerase reverse transcriptase (hTERT) deficiency.

Telomeres are specialized structures providing chromosome integrity during cellular division along with protection against premature senescence and apoptosis. Accelerated telomere attrition in patients with myelodysplastic syndrome (MDS) occurs by an undefined mechanism. Although the MDS clone originates within the myeloid compartment, T-lymphocytes display repertoire contraction and loss of naive T-cells. The replicative lifespan of T-cells is stringently regulated by telomerase activity. In MDS cases, we show that purified CD3+ T-cells have significantly shorter telomere length and reduced proliferative capacity upon stimulation compared with controls. To understand the mechanism, telomerase enzymatic activity and telomerase reverse transcriptase (hTERT), gene expression were compared in MDS cases (n=35) and healthy controls (n=42) within different T-cell compartments. Telomerase activity is greatest in naive T-cells illustrating the importance of telomere repair in homeostatic repertoire regulation. Compared with healthy controls, MDS cases had lower telomerase induction (P<0.0001) that correlated with significantly lower hTERT mRNA (P<0.0001), independent of age and disease stratification. hTERT mRNA deficiency affected naive but not memory T-cells, and telomere erosion in MDS occurred without evidence of an hTERT-promoter mutation, copy number variation or deletion. Telomerase insufficiency may undermine homeostatic control within the hematopoietic compartment and promote a change in the T-cell repertoire in MDS.

[Follow-up of pregnancies with red-cell allo-immunisation: State-of-the art]. / Le point sur le suivi des allo-immunisations érythrocytaires.

Anti-RhD allo-immunisation has become rare since anti-D prophylaxis was introduced in the seventies; however, it remains the first cause of fetal anemia. It may cause severe fetal complications such as fetal hydrops, cerebral anoxic lesions and fetal death. In the neonatal period, severe jaundices and anemias requiring transfusion or exsanguino-transfusion are still common in case of severe allo-immunisation. Neonatal death and sequellae due to bilirubin encephalopathy have not fully disappeared. Follow-up of pregnancies with maternal allo-immunisation requires identification of the antibody (anti-RhD, anti-Kell and anti-c are the most frequently responsible for fetal complications), dosage and titration. In RhD allo-immunization, feto-maternal incompatibility may be confirmed by non-invasive RHD genotyping of the fetus in maternal blood. In cases at risk for fetal anemia, weekly Doppler assessment of middle cerebral artery peak systolic velocity (MCA-PSV) allows identification of fetal anemia before the occurrence of fetal hydrops. The reference treatment of fetal anemia is in utero fetal transfusion. The risk of fetal loss due to in utero transfusion (IUT) is 3% per procedure. The cumulated risk of fetal loss can thus exceed 10% in case of early occurrence of fetal anemia requiring up to five or six IUTs in a single pregnancy.

[Human leptospiroses in the overseas departments and territories: 10 years' immunological diagnosis (1970-1979)]. / Les leptospiroses humaines dans les D. O. M.-T. O. M. 10 années de bilans immunologiques (1970-1979).

In French overseas Departments and Territories, Leptospiroses exist. In the Caribbean zone, human Leptospiroses are frequently found; in Martinique island, and some cases are recorded in French Guyana. In the Indian Ocean, "La Réunion" island, approximately 40 cases are diagnosed every year (mortality rate: 17%). In Polynesian areas, 3 serovars are found. Biological diagnosis is easier now with screening tests. Sera are to be sent to the National Leptospirosis Centre, Paris, for confirmatory test. In fact, the high incidence of Icterohaemorrhagiae serogroup does not seem to reflect the real situation, but represents the severe cases diagnosed in hospitalized patients. Minor cases remain often unnoticed. A survey of human and animal Leptospiroses would give another classification of serogroups frequency. It is important to know that 80% of Leptospiroses occur without jaundice.

Potential interaction between warfarin and dicloxacillin.

OBJECTIVE: To report a case and retrospective review of seven patients who experienced a decrease in prothrombin time during concomitant administration of warfarin and dicloxacillin. CASE SUMMARY: A 41-year-old man receiving warfarin 22 mg/wk with a final baseline prothrombin time (PT) of 20.7 sec was prescribed dicloxacillin 500 mg qid for 10 days. Plasma collected for PT determinations was also used to measure trough warfarin R- and S- enantiomer concentrations. The PT and S- and R-warfarin concentrations decreased 17%, 25%, and 20%, respectively, on day 5 after initiation of dicloxacillin. For the retrospective review, the mean PT decreased 17.0% (range 10.5-25.9%) as soon as 4 days after the initiation of dicloxacillin. DISCUSSION: Our observations, which are consistent with those of two previously published reports, suggest a close temporal relationship between the administration of dicloxacillin and a decreased anticoagulant effect of warfarin. Limited data from our patient further suggest that this may result from declines in systemic warfarin concentrations. The time course of the fall of PTs appears to occur within 4-5 days; return of the PT to baseline after dicloxacillin administration is stopped appears to take up to 3 weeks. Until further controlled studies are conducted to confirm this interaction, clinicians should be aware that patients may be at risk for a decreased anticoagulant effect of warfarin when dicloxacillin is given concomitantly. CONCLUSIONS: Careful monitoring of international normalized ratios and titration of the warfarin dosage is recommended on initiation and for 3 weeks after discontinuation of dicloxacillin in patients receiving warfarin.

Time-resolved transmission through homogeneous scattering media: time-response effects.

An analytical expression has been obtained that describes the time variation of time-resolved signals transmitted through or reflected by a homogeneous scattering slab as measured with a detection system having a square-impulse response. This expression can be used to improve the match between theoretical and experimental time-resolved signals measured with a system having a finite response time. It can also be used to assess the effect of a finite detection response time on the time-domain characterization of a turbid medium. The expression can be adapted to detection systems that are not time invariant.

Inclusion characterization in a scattering slab with time-resolved transmittance measurements: perturbation analysis.

A procedure for the time-domain optical characterization of an inclusion in a scattering slab is investigated theoretically and experimentally. The method relies on the measurement of a contrast function, which is defined as the time-dependent relative change in the transmitted signal resulting from the presence of the inclusion. Analytical expressions for the contrast functions of absorptive and diffusive inclusions are obtained through a perturbation solution of the diffusion equation. This procedure is used successfully to determine the optical properties of absorptive, diffusive, and mixed inclusions located at midplane in a scattering slab by use of time-resolved transmittance measurements.

Time-domain optical imaging: discrimination between scattering and absorption.

A technique for discriminating between scattering and absorbing inclusions located in the center of a scattering slab is presented. The technique is based on an empirical model that provides a simple mathematical expression to describe the change in the time-resolved transmission resulting from the presence of an inclusion. Experimental results from various configurations show that the technique allows for proper recognition of the type of an inclusion whether it is scattering or absorbing. This technique is a significant step toward tissue differentiation.