Efficacy of cefiderocol- vs colistin-containing regimen for treatment of bacteraemic ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii in patients with COVID-19.

INTRODUCTION: Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) in patients hospitalized in intensive care units (ICUs) is an important and challenging complication, including in patients with coronavirus disease 2019 (COVID-19). Considering the poor lung penetration of most antibiotics, including intravenous colistin due to the poor pharmacokinetics/pharmacodynamics at the infection site, the choice of the best antibiotic regimen is still being debated. METHODS: This single-centre, observational study was conducted from March 2020 to August 2022, and included all patients hospitalized consecutively with VAP and concomitant bloodstream infection due to CRAB in the COVID-ICU. The main goal of the study was to evaluate risk factors associated with survival or death at 30 days from VAP onset. A propensity score for receiving therapy was added to the model. RESULTS: During the study period, 73 patients who developed VAP and concomitant positive blood cultures caused by CRAB were enrolled in the COVID-ICU. Of these patients, 67 (91.7%) developed septic shock, 42 (57.5%) had died at 14 days and 59 (80.8%) had died at 30 days. Overall, 54 (74%) patients were treated with a colistin-containing regimen and 19 (26%) were treated with a cefiderocol-containing regimen. Cox regression analysis showed that chronic obstructive pulmonary disease and age were independently associated with 30-day mortality. Conversely, cefiderocol-containing regimens and cefiderocol + fosfomycin in combination were independently associated with 30-day survival, as confirmed by propensity score analysis. CONCLUSIONS: This real-life study in patients with bacteraemic VAP caused by CRAB provides useful suggestions for clinicians, showing a possible benefit of cefiderocol and its association with fosfomycin.

The projection from the primary motor and somatic sensory cortex to the basilar pontine nuclei. A detailed electrophysiological and anatomical study in the rat.

The projections from the primary motor and somatic sensory cortex onto the basilar pontine grey were studied in Wistar Rats injecting microvolumes of WGA-HRP solution in sites of the motor and sensory cortex electrophysiologically identified. The main results may be summarized as follows. (a) The projections from both the motor and sensory cortex were found as rostrocaudally oriented columns of terminals in the basilar pontine nuclei. The projection from the motor cortex extended to all over the rostrocaudal extension of the basilar pontine nuclei. To a rostrocaudal shift of the pontine projection field correspond a rostrocaudal displacement in the motor area. The projection from the sensory cortex was mainly restricted to the caudal two thirds of the basilar pontine nuclei, though the hindlimb region of the sensory cortex also showed a discrete representation in the rostral third of the basilar pontine nuclei. (b) The terminal fields of the motor and sensory cortex were segregated except those in the caudal pontine level, which come from the projection of the hindlimb cortical regions. (c) Within the terminal fields of the projections from the motor as well as from the sensory cortex a clearcut topographical arrangement was observed between the projections of cortical areas controlling the head, the forelimb and the hindlimb regions. (d) Within the location of these major subdivisions, the representations of individual body segments were overlapped for a little part ("convergent zones"), whereas the greater part of their projection zones was selective of each cortical field ("private zones"). In conclusion, the present study showed that the projections from the motor and sensory cortex to the basilar pontine nuclei are arranged with a very precise somatotopical organization.

Effects of cerebellectomy on motivation-related behavior: a time-course study.

The open field behavior and learning capacity of male rats of the Wistar strain was studied 1, 2, and 6 months after cerebellectomy (CBX). The results show a decrease in locomotor activity 1 month after CBX and thereafter a slow recovery. Grooming behavior was still normal after 1 month, but it decreased 2 months after CBX. Learning capacity, as assessed by the shuttle-box test, was remarkably decreased in cerebellectomized animals 1 month after operation. A significant impairment of memory capacity was also observed in rats tested for passive avoidance behavior 2 months after CBX. A partial recovery of this parameter was present 6 months after operation. These results support the hypothesis of a possible influence of cerebellum on motivation-related behaviors, independently of its modulatory role on motricity.

Topographic organization of the cerebellothalamic projections in the rat. An autoradiographic study.

The topographical organization of the subnuclear projections towards the thalamus was studied with autographic methods in adult Wistar rats. The four cerebellar deep nuclei give rise to projections to the ventral region of the rostral thalamus. Most of the fibers end contralaterally, according to a topographical pattern; however, some fibers from each of the cerebellar nuclei recross the midline at the thalamic level and terminate ipsilaterally, within regions symmetric to those receiving the densest contralateral projection. These ipsilateral cerebellothalamic components arise in decreasing order from the caudal nucleus lateralis, the ventrocaudal nucleus medialis and the nucleus interpositus, respectively. The projections of the nucleus lateralis directed to the contralateral thalamus are topographically organized. (1) Within the nucleus ventralis lateralis, the rostral and caudal parts of the cerebellar nucleus lateralis project respectively to rostral and caudal regions; lateral and medial zones of the nucleus lateralis project, respectively, to medial and central aspects of the nucleus ventralis lateralis. (2) The nucleus ventralis medialis and particularly its caudal portion appears to receive the bulk of its afferents from the ventromedial portion of the nucleus lateralis including the "subnucleus lateralis parvocellularis". (3) The nucleus centralis lateralis receives fibers from most parts of the nucleus lateralis including the "dorsolateral hump". (4) The nucleus interpositus anterior projects to the dorsomedial aspect of the rostral nucleus ventralis lateralis. In the latter nucleus, the ventrolateral aspect of the central region receives projections in cases in which the nucleus interpositus posterior is largely involved. A particular emphasis is put on the different projections from the various subnuclear regions of the lateral nucleus. A comparison is attempted with the situation in the primates, particularly with regard to the question of the parvocellular subdivision of the lateral nucleus.