The Funnel: From the Skull Base to the Sacrum. New Trends and Technologies in Anaesthesia for the Adult Patient.

The management of children affected by neurosurgical pathologies is multidisciplinary and should be set on several fronts.The potential need for massive blood components transfusions, the prolonged anaesthesia in paediatric age that may be often complicated by various forms of syndrome-related problems, and airway management are often encountered.The problems may be divided schematically into three large groups: preoperative, intraoperative and postoperative problems.The aim of this work is to optimize and make paediatric neurosurgery safe by highlighting the most important aspects in the various perioperative phases.

Technologies in Anaesthesia for the Paediatric Patient.

Spine surgery is an increasingly frequent surgery and includes a wide range of procedures, from minor surgeries (removal of herniated discs, simple laminectomies) to major surgeries (arthrodesis, removal of spinal meningiomas, etc.).These surgeries commonly involve complex patients (elderly population, ASA II-III) and are sometimes performed in emergency settings (polytrauma, cauda syndrome, pathological fractures), which require specific positions (pronation or lateral decubitus), whereby there can be difficulty in airway management, especially in surgeries that concern the cervical tract.One of the main peculiarities of spine surgery involves the prone position.Patient positioning on the operating bed is an action that must be carried out under medical supervision, in particular by the anaesthetist who is supposed to supervise the regular positioning of the patient at the very moment in which it is performed. The correct positioning of the patient is one of the most important moments of the patient care process in the operating room, given that an error in this field may cause serious damage to the patient by giving rise to permanent and significant nerve damage.The prone position is associated with a variety of complications (Kwee et al., Int Surg 100(2): 292-303, 2015). The points of greatest compression during pronation are eyes, nose, breasts, genitals and neck veins.Therefore, the main risks that can derive from an incorrect position are visual disturbances from inappropriate orbital compression, brachial plexus stretching, ulnar nerve compression and lateral femur-cutaneous nerve stretching. In addition, an inappropriate compression of the abdominal organs in this position, may cause ischemia and consequent organ failure resulting in hospitalization prolongation, permanent disability and sometimes even death (Edgcombe et al., Br J Anaesth 100: 165-183, 2008).In addition to the mechanical effects on anatomical structures, there are also the physiological effects of the prone position, which can be divided into circulatory and respiratory effects.These effects are even more pronounced in elderly patients, cardiopaths or patients with respiratory diseases.

The Role of the Anesthesiologist and the Modern Intraoperative Echography in Ventriculoatrial Shunt for Hydrocephalus: From Hakim to Nowadays.

The introduction of US-guided venipuncture in clinical practice has greatly facilitated the surgical approach to patients with hydrocephalus. Especially in infants and children, where it results in a lower technical failure rate, less time and fewer complications than the traditional referral method, this technique has become a clinical protocol. This dynamic or "real time" technique has become one of the anesthetist's tools. This allowed the anesthesiologists to be part of the surgical team, so they not only dedicate themselves to inducing and maintaining general anesthesia but also to performing venipuncture of the central vein of the neck and to locating the tip of the catheter.The anesthetist's tools have made it possible to perform a simple and safe method, and the anesthesiologists have become an active part of the surgical team, charged with a specific role during the positioning of the ventricular atrial shunt.

Serum HMGB1 levels are independently associated with glucose clamp-derived measures of insulin resistance in women with PCOS.

PURPOSE: PCOS is associated with low grade inflammation which could play a role in insulin resistance and ovarian dysfunction. Preliminary findings suggested that serum levels of HMGB1, a cytokine involved in inflammation, might be altered in women with PCOS. Primary aim of this study was to assess whether HMGB1 serum concentrations are associated with PCOS and with the state of insulin resistance of these women. METHODS: Sixty women with PCOS, selected to have a similar proportion of subjects with altered or normal insulin sensitivity, and 29 healthy controls were studied. Serum HMGB1 levels were compared in subgroups of PCOS women and controls. In PCOS women, insulin sensitivity was assessed by the glucose clamp technique and HMGB1 was measured at baseline and after acute hyperinsulinemia. RESULTS: HMGB1 levels were similar in women with PCOS and controls and no elements used for diagnosing PCOS were associated with serum HMGB1. However, HMGB1 concentrations were higher in insulin-resistant vs insulin-sensitive PCOS women (p = 0.017), and inversely associated with insulin-induced total and non-oxidative glucose metabolism. In both subgroups of PCOS women, serum HMBG1 levels significantly increased after acute hyperinsulinemia. CONCLUSIONS: These data suggest that HMGB1 levels are not associated with PCOS per se, but with insulin resistance. Further research should establish the underlying nature of this relationship, and whether this protein might play a role in the metabolic complications of PCOS.

Trimester-specific reference intervals for thyroid function parameters in pregnant Caucasian women using Roche platforms: a prospective study.

BACKGROUND: Standard thyroid function parameters reference intervals (RI) are unsuitable during pregnancy, potentially resulting in incongruous treatments that may cause adverse effects on pregnancy outcomes. We aimed at defining trimester-specific TSH, FT4 and FT3 RI, using samples longitudinally collected from healthy Caucasian women. MATERIALS AND METHODS: Blood samples from 150 healthy Caucasian women, who had a physiological gestation and a healthy newborn at term, were collected in each trimester and at around six months post-partum. They showed mild iodine deficiency. After excluding women with overt TSH abnormalities (> 10 mU/L) and/or TPO antibodies, data from 139 pregnant women were analyzed by means of widely used Roche platforms, and TSH, FT4 and FT3 trimester-specific RI were calculated. Post-partum data were available for 55 subjects. RESULTS: Serum TSH RI were 0.34-3.81 mU/L in the first trimester, and changed slightly to 0.68-4.07 U/L and 0.63-4.00 mU/L in the second and third trimester, respectively. Conversely, both FT4 and FT3 concentrations progressively decreased during pregnancy, the median values in the third trimester being 14.8% and 13.2% lower, respectively, than in the first trimester. Thyroid function parameters in the first trimester were similar to those measured after the end of pregnancy. CONCLUSIONS: This study calculates trimester-specific RI for thyroid function parameters in pregnancy, and proposes the reference limits that should be adopted when using Roche platforms in Caucasian women.

Association of Cognitive Performance with Frailty in Older Individuals with Cognitive Complaints.

OBJECTIVES: Frailty is a risk factor for poor cognitive performance in older adults. However, few studies have evaluated the association of cognitive performance with frailty in a low- to middle-income country (LMIC). This study aimed to investigate an association between cognitive performance and frailty in older adults with memory complaints in Brazil. Secondarily, we aim to assess an association of cognitive performance with gait speed and grip strength. DESIGN: Cross-sectional study. SETTING: Outpatient service from a LMIC. PARTICIPANTS: Older adults with memory complaints reported by the participants, their proxies, or their physicians. MEASUREMENTS: Frailty was evaluated using the Cardiovascular Health Study criteria. A neuropsychological battery evaluated memory, attention, language, visuospatial function, executive function. Linear regression analysis with adjustment for age, sex, and education was used. We also evaluated the interaction of education with frailty, grip strength, and gait speed. RESULTS: Prefrailty was associated with poor performance in the memory domain, as well as slower gait speed was associated with worse performance in memory, attention, language, and executive function. Frailty and grip strength were not associated with cognitive performance. Interactions of education with gait speed were significant for global performance, as well as for attention and visuospatial ability. CONCLUSION: In elderly patients with memory complaints, prefrailty was associated with poor memory performance. Slowness was associated with poorer performance in some cognitive domains, mainly in participants with low education.

Juno's Close Encounter With Ganymede-An Overview.

The Juno spacecraft has been in orbit around Jupiter since 2016. Two flybys of Ganymede were executed in 2021, opportunities realized by evolution of Juno's polar orbit over the intervening 5 years. The geometry of the close flyby just prior to the 34th perijove pass by Jupiter brought the spacecraft inside Ganymede's unique magnetosphere. Juno's payload, designed to study Jupiter's magnetosphere, had ample dynamic range to study Ganymede's magnetosphere. The Juno radio system was used both for gravity measurements and for study of Ganymede's ionosphere. Remote sensing of Ganymede returned new results on geology, surface composition, and thermal properties of the surface and subsurface.

Major adverse cardiovascular events associated with VEGF-targeted anticancer tyrosine kinase inhibitors: a real-life study and proposed algorithm for proactive management.

BACKGROUND: Vascular endothelial growth factor receptor (VEGFR)-targeted tyrosine kinase inhibitors (TKIs) are widely used in cancer treatment and burdened by cardiovascular toxicity. The majority of data come from clinical trials, thus in selected populations. The aim of our study is to evaluate the cardiotoxicity profile of VEGFR-targeted TKIs and the impact of cardiovascular risk factors in a real-life population. PATIENTS AND METHODS: In this cohort, population-based study, patients treated with VEGFR-targeted TKIs, bevacizumab and trastuzumab between 2009 and 2014 were analyzed. A multi-source strategy for data retrieval through hospital, pharmaceutical and administrative databases of the Lombardy region, Italy, has been adopted. The primary endpoint was to determine the incidence and type of major adverse cardiovascular events (MACEs) along with their temporal trend. The secondary endpoint was to define the impact of cardiovascular risk factors in the occurrence of MACEs. RESULTS: A total of 829 patients were treated with VEGFR-targeted TKIs. Eighty-one MACEs occurred in the first year of follow-up [crude cumulative incidence (CCI): 9.79%] mainly consisting of arterial thrombotic events (ATEs, 31 events, CCI: 3.99%), followed by rhythm disorders (22 events, CCI: 2.66%), pulmonary embolisms and heart failures (13 events each, CCI: 1.57%). While the incidence of most MACEs showed a plateau after 6 months, ATEs kept increasing along the year of follow-up. Hypertension and dyslipidemia were associated with an increase in risk of ATEs [relative risk difference (RRD) +209.8% and +156.2%, respectively], while the presence of previous MACEs correlated with a higher risk of all MACEs in multivariate analysis (RRD 151.1%, 95% confidence interval 53.6% to 310.3%, P < 0.001). CONCLUSIONS: MACEs occur in a clinically significant proportion of patients treated with VEGFR-targeted TKIs, with ATEs being predominant, mainly associated with hypertension and dyslipidemia. A clinical algorithm for effective proactive management of these patients is warranted.

Role of the pupillometer in the assessment of pain in the sedation of pediatric patients.

OBJECTIVE: Pupillometry has been used to assess pain intensity and response to analgesic drugs in adults. The aim of this study was to verify the usefulness and effectiveness of the pupillometer to assess pain and depth of sedation in pediatric patients undergoing painful procedures and to optimize pain management by observing pupillary variations induced by opioids. PATIENTS AND METHODS: This is a prospective, monocentric study conducted in the sedation room of the Pediatric Intensive Care Unit of Fondazione Policlinico A. Gemelli in Rome. A population of 22 pediatric patients who underwent painful procedures was enrolled. Eleven children were sedated by opioid drugs. Heart rate, systolic blood pressure, diastolic blood pressure, bispectral index, maximum pupil size (Size), pupil change (CH), Neurological Pupil Index (NPi) were collected over four times: before starting the procedure; before the painful stimulus (when the patient was sedated); when the painful stimulus was applied; at the end of the procedure. A NeurOptics NPi-200 pupillometer was used for the study. RESULTS: Statistical significance in the variation of haemodynamic parameters was less significant than the variation obtained by analyzing the pupillary parameters: a significant change in NPi and CH in the transition from wakefulness to sedation and from the application of the painful stimulus to awakening was found in both study populations, patients who have received opioids and patients who have not received opioids. Changes in the mean CH of the pupil diameter correlate with the depth of sedation, and the size values vary in relation to the administration of opioids. CONCLUSIONS: Our findings highlight the potential role of pupillometry as a non-invasive method to objectively quantitate pain response in children to reach an efficient analgesic approach.

Strategies to tackle RAS-mutated metastatic colorectal cancer.

The RAS oncogene is among the most commonly mutated in cancer. RAS mutations are identified in about half of patients diagnosed with metastatic colorectal cancer (mCRC), conferring poor prognosis and lack of response to anti-epidermal growth factor receptor (EGFR) antibodies. In the last decades, several investigational attempts failed in directly targeting RAS mutations, thus RAS was historically regarded as 'undruggable'. Recently, novel specific KRASG12C inhibitors showed promising results in different solid tumors, including mCRC, renewing interest in this biomarker as a target. In this review, we discuss different strategies of RAS targeting in mCRC, according to literature data in both clinical and preclinical settings. We recognized five main strategies focusing on those more promising: direct RAS targeting, targeting the mitogen-activated protein kinase (MAPK) pathway, harnessing RAS through immunotherapy combinations, RAS targeting through metabolic pathways, and finally other miscellaneous approaches. Direct KRASG12C inhibition is emerging as the most promising strategy in mCRC as well as in other solid malignancies. However, despite good disease control rates, tumor response and duration of response are still limited in mCRC. At this regard, combinational approaches with anti-epidermal growth factor receptor drugs or checkpoint inhibitors have been proposed to enhance treatment efficacy, based on encouraging results achieved in preclinical studies. Besides, concomitant therapies increasing metabolic stress are currently under evaluation and expected to also provide remarkable results in RAS codon mutations apart from KRASG12C. In conclusion, based on hereby reported efforts of translational research, RAS mutations should no longer be regarded as 'undruggable' and future avenues are now opening for translation in the clinic in mCRC.

Insulin resistance and PCOS: chicken or egg?

PCOS is a common and heterogeneous endocrine disorder in women of reproductive age, frequently associated with metabolic abnormalities. It was estimated that about 75% of these subjects have an impairment of insulin action, as measured by gold standard methods. While the relationship between insulin resistance and PCOS is consistently shown by a number of studies, the mechanisms underlying its primary origin still remains an unsolved issue. Insulin resistance and the associated hyperinsulinemia can induce both the endocrine and reproductive traits of PCOS. However, androgen excess, in turn, can impair insulin action, directly and/or through several changes occurring in different tissues. Body fat excess, which is another common feature in these women, can contribute to worsening the whole picture. Nevertheless, insulin resistance may also be found in many normal-weight individuals. Endocrine and metabolic abnormalities can develop in different moments, and probably there is fetal programming of these alterations. However, a number of vicious circles, with bidirectional relationships between androgen excess and insulin resistance, and with the contribution of several other factors, make it extremely difficult to understand where this process really originates. This review summarizes available evidence on this topic, in order to better understand the complex relationships linking hyperandrogenism and impaired insulin action in women with PCOS.

Correction of the VIR-visible dataset from the Dawn mission at Vesta.

This work describes the correction method applied to the dataset acquired at the asteroid (4) Vesta by the visible channel of the visible and infrared mapping spectrometer. The rising detector temperature during data acquisitions in the visible wavelengths leads to a spectral slope increase over the whole spectral range. This limits the accuracy of the studies of the Vesta surface in this wavelength range. Here, we detail an empirical method to correct for the visible detector temperature dependency while taking into account the specificity of the Vesta dataset.

Impact heat driven volatile redistribution at Occator crater on Ceres as a comparative planetary process.

Hydrothermal processes in impact environments on water-rich bodies such as Mars and Earth are relevant to the origins of life. Dawn mapping of dwarf planet (1) Ceres has identified similar deposits within Occator crater. Here we show using Dawn high-resolution stereo imaging and topography that Ceres' unique composition has resulted in widespread mantling by solidified water- and salt-rich mud-like impact melts with scattered endogenic pits, troughs, and bright mounds indicative of outgassing of volatiles and periglacial-style activity during solidification. These features are distinct from and less extensive than on Mars, indicating that Occator melts may be less gas-rich or volatiles partially inhibited from reaching the surface. Bright salts at Vinalia Faculae form thin surficial precipitates sourced from hydrothermal brine effusion at many individual sites, coalescing in several larger centers, but their ages are statistically indistinguishable from floor materials, allowing for but not requiring migration of brines from deep crustal source(s).

Tropomyosin receptor kinase (TRK) biology and the role of NTRK gene fusions in cancer.

The tropomyosin receptor kinase (TRK) family of receptor tyrosine kinases are encoded by NTRK genes and have a role in the development and normal functioning of the nervous system. Since the discovery of an oncogenic NTRK gene fusion in colorectal cancer in 1986, over 80 different fusion partner genes have been identified in a wide array of adult and paediatric tumours, providing actionable targets for targeted therapy. This review describes the normal function and physiology of TRK receptors and the biology behind NTRK gene fusions and how they act as oncogenic drivers in cancer. Finally, an overview of the incidence and prevalence of NTRK gene fusions in various types of cancers is discussed.

Correction of the VIR-visible data set from the Dawn mission.

Data acquired at Ceres by the visible channel of the Visible and InfraRed mapping spectrometer (VIR) on board the NASA Dawn spacecraft are affected by the temperatures of both the visible (VIS) and the infrared (IR) sensors, which are, respectively, a charged coupled device and a HgCdTe array. The variations of the visible channel temperatures measured during the sessions of acquisitions are correlated with the variations in the spectral slope and shape for all the mission phases. The IR channel temperature is more stable during the acquisitions; nonetheless, it is characterized by a bimodal distribution whether the cryocooler (and, therefore, the IR channel) is used or not during the visible channel operations. When the infrared channel temperature is high (175 K, i.e., not in use and with the cryocooler off), an additional negative slope and a distortion are observed in the spectra of the visible channel. We developed an empirical correction based on a reference spectrum for the whole dataset; it is designed to correct the two issues related to the sensor temperatures that we have identified. The reference spectrum is calculated to be representative of the global Ceres' surface. It is also made of the data acquired when the visible and infrared channel temperatures are equal to the ones measured during an observation of the Arcturus star by VIR, which is consistent with several ground-based observations. The developed correction allows reliable analysis and mapping to be performed by minimizing the artifacts induced by fluctuations of the VIS temperature. Thanks to this correction, a direct comparison between different mission phases during which the VIR experienced different visible and infrared channel temperatures is now possible.

Spontaneous pulmonary air embolism in a child undergoing procedural deep sedation: case report and review of the literature.

We performed a systematic review of the literature starting from a real case of venous air embolism (VAE) in a young infant undergoing central catheterization during procedural sedation. Air embolism due to internal jugular vein catheterization during procedural sedation is very rare, but it is a potentially life-threatening complication of central catheterization that warrants attention. To our knowledge, this is the first case published in a similar scenario.

Juno observations of spot structures and a split tail in Io-induced aurorae on Jupiter.

Jupiter's aurorae are produced in its upper atmosphere when incoming high-energy electrons precipitate along the planet's magnetic field lines. A northern and a southern main auroral oval are visible, surrounded by small emission features associated with the Galilean moons. We present infrared observations, obtained with the Juno spacecraft, showing that in the case of Io, this emission exhibits a swirling pattern that is similar in appearance to a von Kármán vortex street. Well downstream of the main auroral spots, the extended tail is split in two. Both of Ganymede's footprints also appear as a pair of emission features, which may provide a remote measure of Ganymede's magnetosphere. These features suggest that the magnetohydrodynamic interaction between Jupiter and its moon is more complex than previously anticipated.

Clusters of cyclones encircling Jupiter's poles.

The familiar axisymmetric zones and belts that characterize Jupiter's weather system at lower latitudes give way to pervasive cyclonic activity at higher latitudes. Two-dimensional turbulence in combination with the Coriolis ß-effect (that is, the large meridionally varying Coriolis force on the giant planets of the Solar System) produces alternating zonal flows. The zonal flows weaken with rising latitude so that a transition between equatorial jets and polar turbulence on Jupiter can occur. Simulations with shallow-water models of giant planets support this transition by producing both alternating flows near the equator and circumpolar cyclones near the poles. Jovian polar regions are not visible from Earth owing to Jupiter's low axial tilt, and were poorly characterized by previous missions because the trajectories of these missions did not venture far from Jupiter's equatorial plane. Here we report that visible and infrared images obtained from above each pole by the Juno spacecraft during its first five orbits reveal persistent polygonal patterns of large cyclones. In the north, eight circumpolar cyclones are observed about a single polar cyclone; in the south, one polar cyclone is encircled by five circumpolar cyclones. Cyclonic circulation is established via time-lapse imagery obtained over intervals ranging from 20 minutes to 4 hours. Although migration of cyclones towards the pole might be expected as a consequence of the Coriolis ß-effect, by which cyclonic vortices naturally drift towards the rotational pole, the configuration of the cyclones is without precedent on other planets (including Saturn's polar hexagonal features). The manner in which the cyclones persist without merging and the process by which they evolve to their current configuration are unknown.

Pitted terrains on (1) Ceres and implications for shallow subsurface volatile distribution.

Prior to the arrival of the Dawn spacecraft at Ceres, the dwarf planet was anticipated to be ice-rich. Searches for morphological features related to ice have been ongoing during Dawn's mission at Ceres. Here we report the identification of pitted terrains associated with fresh Cerean impact craters. The Cerean pitted terrains exhibit strong morphological similarities to pitted materials previously identified on Mars (where ice is implicated in pit development) and Vesta (where the presence of ice is debated). We employ numerical models to investigate the formation of pitted materials on Ceres and discuss the relative importance of water ice and other volatiles in pit development there. We conclude that water ice likely plays an important role in pit development on Ceres. Similar pitted terrains may be common in the asteroid belt and may be of interest to future missions motivated by both astrobiology and in situ resource utilization.

Tracking a CAD-ALK gene rearrangement in urine and blood of a colorectal cancer patient treated with an ALK inhibitor.

BACKGROUND: Monitoring response and resistance to kinase inhibitors is essential to precision cancer medicine, and is usually investigated by molecular profiling of a tissue biopsy obtained at progression. However, tumor heterogeneity and tissue sampling bias limit the effectiveness of this strategy. In addition, tissue biopsies are not always feasible and are associated with risks due to the invasiveness of the procedure. To overcome these limitations, blood-based liquid biopsy analysis has proven effective to non-invasively follow tumor clonal evolution. PATIENTS AND METHODS: We exploited urine cell-free, trans-renal DNA (tr-DNA) and matched plasma circulating tumor DNA (ctDNA) to monitor a metastatic colorectal cancer patient carrying a CAD-ALK translocation during treatment with an ALK inhibitor. RESULTS: Using a custom next generation sequencing panel we identified the genomic CAD-ALK rearrangement and a TP53 mutation in plasma ctDNA. Sensitive assays were developed to detect both alterations in urine tr-DNA. The dynamics of the CAD-ALK rearrangement in plasma and urine were concordant and paralleled the patient's clinical course. Detection of the CAD-ALK gene fusion in urine tr-DNA anticipated radiological confirmation of disease progression. Analysis of plasma ctDNA identified ALK kinase mutations that emerged during treatment with the ALK inhibitor entrectinib. CONCLUSION: We find that urine-based genetic testing allows tracing of tumor-specific oncogenic rearrangements. This strategy could be effectively applied to non-invasively monitor tumor evolution during therapy. The same approach could be exploited to monitor minimal residual disease after surgery with curative intent in patients whose tumors carry gene fusions. The latter could be implemented without the need of patient hospitalization since urine tr-DNA can be self-collected, is stable over time and can be shipped at specified time-points to central labs for testing.