Predicting CPAP failure after less invasive surfactant administration (LISA) in preterm infants by machine learning model on vital parameter data: a pilot study.

Objective. Less invasive surfactant administration (LISA) has been introduced to preterm infants with respiratory distress syndrome on continuous positive airway pressure (CPAP) support in order to avoid intubation and mechanical ventilation. However, after this LISA procedure, a significant part of infants fails CPAP treatment (CPAP-F) and requires intubation in the first 72 h of life, which is associated with worse complication free survival chances. The aim of this study was to predict CPAP-F after LISA, based on machine learning (ML) analysis of high resolution vital parameter monitoring data surrounding the LISA procedure.Approach. Patients with a gestational age (GA) <32 weeks receiving LISA were included. Vital parameter data was obtained from a data warehouse. Physiological features (HR, RR, peripheral oxygen saturation (SpO2) and body temperature) were calculated in eight 0.5 h windows throughout a period 1.5 h before to 2.5 h after LISA. First, physiological data was analyzed to investigate differences between the CPAP-F and CPAP-Success (CPAP-S) groups. Next, the performance of two types of ML models (logistic regression: LR, support vector machine: SVM) for the prediction of CPAP-F were evaluated.Main results. Of 51 included patients, 18 (35%) had CPAP-F. Univariate analysis showed lower SpO2, temperature and heart rate variability (HRV) before and after the LISA procedure. The best performing ML model showed an area under the curve of 0.90 and 0.93 for LR and SVM respectively in the 0.5 h window directly after LISA, with GA, HRV, respiration rate and SpO2as most important features. Excluding GA decreased performance in both models.Significance. In this pilot study we were able to predict CPAP-F with a ML model of patient monitor signals, with best performance in the first 0.5 h after LISA. Using ML to predict CPAP-F based on vital signals gains insight in (possibly modifiable) factors that are associated with LISA failure and can help to guide personalized clinical decisions in early respiratory management.

Diagnostic-driven management of invasive fungal disease in hematology in the era of prophylaxis and resistance emergence: Dutch courage?

Patients receiving intensive anti-leukemic treatment or recipients of allogeneic hematopoietic stem cell transplantation (HSCT) are prone to develop invasive fungal disease caused by both Aspergillus and non-Aspergillus moulds. Overall mortality following invasive mould disease (IMD) is high; adequate and timely antifungal treatment seems to ameliorate the outcome, yet early diagnosis in the haematological patient remains a challenge for most clinicians. Prophylaxis and the empiric addition of antifungal therapy to neutropaenic patients with fever persisting or recurring during broad-spectrum antibiotic treatment is therefore standard of care in many institutions. However, aside from the potential for overtreatment and important side effects, the emergence of resistance to medical triazoles in Aspergillus fumigatus poses a risk for inadequate initial treatment. Initial voriconazole therapy in patients with azole-resistant invasive aspergillosis was recently shown to be associated with a 23% increased mortality rate compared to the patients with azole-susceptible infection, despite changing to appropriate antifungal therapy once resistance was detected. Moreover, fever is not always present with IMD; therefore, cases may be missed when relying solely on this symptom for starting diagnostic procedures and antifungal treatment. At our institution, a diagnostic-driven treatment approach for IMD was implemented relying on clinical but also laboratory markers to start antifungal treatment. We describe the basis and clinical implementation of our diagnostic-driven approach in this review.

The long-term outcome of antenatal hydronephrosis up to 15 millimetres justifies a noninvasive postnatal follow-up.

AIM: To assess the incidence of urinary tract infections (UTIs) and surgery in infants with different grades of antenatal hydronephrosis (ANH) and to evaluate incidence, severity and course of underlying vesicoureteral reflux (VUR). METHODS: Retrospective data of 125 infants with ANH were collected. The patients were divided into two groups according to the anterior-posterior pelvis diameter: group I, 5-14 mm and group II, > or =15 mm. RESULTS: UTIs developed in 4 of 106 infants from group I and 5 of 19 infants from group II. Surgical interventions were performed on 1 of 106 patients of group I and 7 of 19 patients of group II. These differences were statistically significant (p-values 0.004 and <0.001, respectively). In group I, 6 of 106 patients had VUR; none of them required surgical intervention and only two developed a UTI (one of whom also had contralateral ureteropelvic junction obstruction). Five of 19 infants in group II had underlying VUR, four of them with associated anomalies, 1 infant required surgical correction and 4 developed UTIs. CONCLUSION: Infants with ANH up to 15 mm have a low incidence of UTIs and surgery and a low incidence and benign course of underlying VUR. Therefore, noninvasive postnatal follow-up is justified and standard voiding cystourethrography should not be performed, but only in cases of ureteric dilatation.

[Diagnostic image (321). A girl with 'bruises' on her abdomen]. / Diagnose in beeld (321). Een meisje met 'blauwe' plekken op de buik. Erythema ab igne.

A 12-year-old girl presented with a reticular skin abnormality on her abdomen, which was caused by the frequent use of hot water bottles to relieve her chronic stomachache. This skin condition is called erythema ab igne.

A quantitative analysis of the development of the pyramidal tract in the cervical spinal cord in the rat.

A quantitative electron microscopic analysis was undertaken of the development of the pyramidal tract, at the level of the third cervical spinal segment, in rats ranging in age from the day of birth to three months old. The axon number was calculated as the product of axon density, determined in a systematic random sample of electron micrographs, and tract area. During the first postnatal week the tract contains thin unmyelinated axons and growth cones. Growth cones are abundant in neonatal rats, but can still be observed occasionally at the end of the first postnatal week, indicating a continuous addition of pyramidal tract axons during the first postnatal week. Myelination starts around P10. By the end of the first postnatal month approximately 50% of the axons have already been myelinated. Myelination proceeds during further maturation, but in the three month old rat 28% of the axons are still unmyelinated. The total number of axons increases rapidly after birth up to 153,000 at the fourth postnatal day. Subsequently, the number of axons is reduced by nearly 50% to 79,000 in the adult rat. The axon loss is most prominent during the second postnatal week, when 32,000 axons are eliminated, but continues for several weeks at a slower rate.

Immunocytochemical distribution of the protein kinase C substrate B-50 (GAP43) in developing rat pyramidal tract.

The neuron-specific phosphoprotein B-50 is a major substrate of kinase C in fetal nerve growth cones, neonatal neural and synaptosomal plasma membranes. B-50 is identical to a growth-associated protein GAP43. Similarly, increases in B-50 occur during rat brain development, neuronal differentiation and axon regeneration. To document the relation between the expression of B-50 and the outgrowth of central axons, we studied B-50 in the developing pyramidal tract in rats at postnatal days 2, 7 and 90 (P2, P7 and P90), at the third cervical spinal segment C3, using affinity-purified antibodies to B-50. At P2 and P7, when outgrowth of pyramidal tract fibers is occurring, B-50 immunoreactivity (BIR) is intense in these fibers. BIR is reduced from P2 to P7 in the ascending fiber tracts of the cuneatus and the gracilis, which develop earlier. At P90 when most of the dorsal funiculus fibers have reached their targets and many are myelinated, BIR is dramatically reduced. In agreement, a 10-fold decrease in B-50 content was measured at P90, as compared to P7. Therefore, our results indicate that B-50 is only expressed relatively abundant in axons of the funiculus posterior during outgrowth. By inference, B-50 may be a differentiating marker to detect elongating fibers.

On the development of the pyramidal tract in the rat. II. An anterograde tracer study of the outgrowth of the corticospinal fibers.

An anterograde tracer study has been made of the developing corticospinal tract (CST) in the rat using wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP). Analysis of normal Rager stained material revealed that corticospinal axons reach upper cervical spinal cord levels at the day of birth (PO). Postnatal rats ranging in age from one (P1) to fourteen (P14) days received multiple WGA-HRP injections into the cortex of their left hemisphere and were allowed to survive for 24 h. The first labeled CST fibers caudally extend into the third thoracic spinal cord segment at P1; into the eighth thoracic segment at P3; into the first or second lumbar segment at P7 and into the second to third sacral segment at Pg. Thus the outgrowth of the leading 'pioneer' fibers of the CST is completed at P9 but later developing axons are continuously added even beyond P9. Quantitative analysis of the amount of label along the length of the outgrowing CST revealed a characteristic pattern of labeling varying with age. The most striking features of that pattern are: the formation of two standing peaks at the level of the cervical and lumbar enlargements respectively and the transient presence of a smaller running peak which moves caudally with the front of the outgrowing bundle. The standing peaks are ascribed to the branching of the axon terminals at both intumescences, whereas the running peak probably arises by the accumulation of tracer within the growth cones at the tips of the outgrowing CST axons. Factors such as the number of axons, the varying axon diameters, the branching collaterals, the presence of varicosities, the transport rate of the tracer, the uptake of the tracer at the injection site, which possibly may affect the amount of label present in both the entire bundle and in the individual axons are discussed. Current research is focused upon an analysis of the relation between the site of injection within the cortex and the pattern of labeling of the CST. A delay of two days was found between the arrival of the CST axons at a particular spinal cord level and their outgrowth into the adjacent spinal gray. However, combined HRP and electronmicroscopic experiments are necessary to determine the factors behind the maturation of the CST as well as the maturation of the spinal gray.

On the development of the pyramidal tract in the rat. I. The morphology of the growth zone.

An electron microscopic study has been made of the tip of the growing pyramidal tract in the rat. This part of the developing bundle, designated as the growth-zone, has been examined at the levels of the medulla oblongata and the third spinal segment at embryonic day 20 and on the day of birth, respectively. The tip of the pyramidal tract contains, apart from axons, numerous larger profiles. An analysis of serial sections revealed that these represent either growth cones or preterminal periodic varicosities. In the growth cones of the corticospinal axons three zones can be distinguished: a proximal "tubular", an intermediate "vesicular-reticular" and a distal "fine-granular" zone. As distinct from the classical descriptions the corticospinal growth cones end in a single or, less frequently, in two more or less parallel filopodia. None of the growth cones analyzed in this study showed multiple filopodia radiating from the terminal expansion as observed at the end of growing axons in tissue cultures and in developing spinal fibre tracts of nonmammalian vertebrates. As regards the varicosities, most of these structures are characterized by a light cytoplasmic density. Others, however, contain a denser cytoplasm, closely resembling that of the vesiculo-reticular part of growth cones.

On the development of the spinal cord of the clawed frog, Xenopus laevis. I. Morphogenesis and histogenesis.

The morphogenesis and histogenesis of the spinal cord of Xenopus were examined. The study encompasses the developmental period between stage 41 and stage 66 (stages according to Nieuwkoop and Faber 1967). This period can roughly be divided into three phases. From stage 50 up to stage 53 strong proliferation and rapid growth are the most striking features. This developmental phase is preceded and followed by less dynamic periods. From stage 41 up to stage 50 the rate of proliferation is relatively low. The numbers of cells in the matrix and in the mantle layer are very small. In the mantle layer two classes of early differentiated transient neurons can be distinguished: primitive giant sensory or Rohon-Beard cells and primitive motor neurons. From stage 46 onward the originally tube-shaped spinal cord swells at the thoracic level into a thoracic enlargement. After stage 50 the proliferation strongly increases until a maximum at stage 53. Concomitantly a considerable acceleration of growth takes place. The major part of the mitoses are always concentrated in the dorsal part of the matrix. From stage 51 onward the cervical and lumbar regions show much more mitoses than the thoracic part. Distinct cervical and lumbar enlargements develop and are going to mask the thoracic swelling of the cord. From stage 54 on proliferation continues on an increasingly low level. The period between stage 54 and stage 66 is characterized by differentiation of the spinal neuronal elements.

On the development of the spinal cord of the clawed frog, Xenopus laevis. II. Experimental analysis of differentiation and migration.

In order to determine the time and site of origin and the final location of various cell groups in the spinal cord, tadpoles of Xenopus laevis, ranging from stage 48 to stage 56 were treated with tritiated thymidine and sacrificed at various stages from 49 to 66 (stages according to Nieuwkoop and Faber (1967). From the poorly developed matrix at stage 48-49 not only ventral horn cells, but also neuroblasts of the intermediate zone and the dorsal horn arise. Both the matrix and the ventricle expand in a dorsal direction. From the well-developed matrix at stage 54, in which the mitotic activity is almost exclusively confined to its dorsal part, mainly cells of the dorsal horn develop. However, this later-stage matrix also gives rise to a considerable number of neuroblasts, which become located in the central parts of the intermediate zone and the ventral horn. Generally the later-born cells come to lie dorsomedially to the older ones. The neuroblasts of the lateral motor column, however, migrate through and settle ventrolaterally to their predecessors. Our observations do not support the basal plate-alar plate concept of His (1893).