The Effects of the Pericapsular Nerve Group Block on Postoperative Pain in Patients with Hip Fracture: A Multicenter Study.

BACKGROUND: An adequate early mobilization followed by an effective and pain-free rehabilitation are critical for clinical and functional recovery after hip and proximal femur fracture. A multimodal approach is always recommended so as to reduce the administered dose of analgesics, drug interactions, and possible side effects. Peripheral nerve blocks should always be considered in addition to spinal or general anesthesia to prolong postoperative analgesia. The pericapsular nerve group (PENG) block appears to be a less invasive and more effective analgesia technique compared to other methods. METHODS: We conducted multicenter retrospective clinical research, including 98 patients with proximal femur fracture undergoing osteosynthesis surgery within 48 h of occurrence of the fracture. Thirty minutes before performing spinal anesthesia, 49 patients underwent a femoral nerve (FN) block plus a lateral femoral cutaneous nerve (LCFN) block, and the other 49 patients received a PENG block. A non-parametric Wilcoxon-Mann-Whitney (α = 0.05) test was performed to evaluate the difference in resting and dynamic numerical rating scale (NRS) at 30 min, 6 h, 12 h, and 24 h. RESULTS: the PENG block administration was more effective in reducing pain intensity compared to the FN block in association with the LFCN block, as seen in the resting and dynamic NRS at thirty minutes and 12 h follow-up. CONCLUSION: the PENG block was more effective in reducing pain intensity than the femoral nerve block associated with the lateral femoral cutaneous nerve block in patients with proximal femur fracture undergoing to osteosynthesis.

Cardiovascular Side Effects of Anthracyclines and HER2 Inhibitors among Patients with Breast Cancer: A Multidisciplinary Stepwise Approach for Prevention, Early Detection, and Treatment.

Cardiovascular (CV) diseases (CVD) are a major cause of long-term morbidity and mortality affecting life expectancy amongst cancer survivors. In recent years, because of the possibility of early diagnosis and the increased efficacy of neo-adjuvant and adjuvant systemic treatments (targeting specific molecular pathways), the high percentage of survival from breast cancer led CVD to become the first cause of death among survivors. Therefore, it is mandatory to adopt cardioprotective strategies to minimize CV side effects and CVD in general in breast cancer patients. Cancer therapeutics-related cardiac dysfunction (CTRCD) is a common group of side effects of chemotherapeutics widely employed in breast cancer (e.g., anthracycline and human epidermal growth factor receptor 2 inhibitors). The aim of the present manuscript is to propose a pragmatic multidisciplinary stepwise approach for prevention, early detection, and treatment of cardiotoxicity in patients with breast cancer.

Acute Heart Failure: Diagnostic-Therapeutic Pathways and Preventive Strategies-A Real-World Clinician's Guide.

Acute heart failure (AHF) is the most frequent cause of unplanned hospital admission in patients of >65 years of age and it is associated with significantly increased morbidity, mortality, and healthcare costs. Different AHF classification criteria have been proposed, mainly reflecting the clinical heterogeneity of the syndrome. Regardless of the underlying mechanism, peripheral and/or pulmonary congestion is present in the vast majority of cases. Furthermore, a marked reduction in cardiac output with peripheral hypoperfusion may occur in most severe cases. Diagnosis is made on the basis of signs and symptoms, laboratory, and non-invasive tests. After exclusion of reversible causes, AHF therapeutic interventions mainly consist of intravenous (IV) diuretics and/or vasodilators, tailored according to the initial hemodynamic status with the addition of inotropes/vasopressors and mechanical circulatory support if needed. The aim of this review is to discuss current concepts on the diagnosis and management of AHF in order to guide daily clinical practice and to underline the unmet needs. Preventive strategies are also discussed.

Exploring the Cardiotoxicity Spectrum of Anti-Cancer Treatments: Definition, Classification, and Diagnostic Pathways.

Early detection and treatment of cancer have led to a noticeable reduction in both mortality and morbidity. However, chemotherapy and radiotherapy could exert cardiovascular (CV) side effects, impacting survival and quality of life, independent of the oncologic prognosis. In this regard, a high clinical index of suspicion is required by the multidisciplinary care team in order to trigger specific laboratory tests (namely natriuretic peptides and high-sensitivity cardiac troponin) and appropriate imaging techniques (transthoracic echocardiography along with cardiac magnetic resonance, cardiac computed tomography, and nuclear testing (if clinically indicated)), leading to timely diagnosis. In the near future, we do expect a more tailored approach to patient care within the respective community along with the widespread implementation of digital health tools.

Plazomicin against Multidrug-Resistant Bacteria: A Scoping Review.

Plazomicin is a next-generation semisynthetic aminoglycoside antibiotic that can be used to treat infections by multi-resistant bacteria. It is effective against many bacteria-producing carbapenemases or other specific hydrolases. This scoping review aims to define the role acquired by plazomicin from its approval by the FDA (US Food and Drug Administration) in 2018 to the present day. Furthermore, we aim to provide a base for a future meta-analysis. This project was conducted following the recommendations presented in the PRISMA extension for scoping reviews and the JBI Manual for Evidence Synthesis. Among 901 potentially engaging citations, 345 duplicates were removed, and only 81 articles were selected for the analysis. According to the data analysis, plazomicin has been used to treat urinary tract infections, bloodstream infections, and ventilation-associated pneumonia. The pathogens killed included multi-resistant E. coli, K. pneumoniae, A. baumannii, P. aeruginosa, and S. aureus. Plazomicin can be a manageable, valid non-beta-lactam alternative for treating multi-resistant bacteria infections.

Opioid sparing effect of intravenous dexmedetomidine in orthopaedic surgery: a retrospective analysis.

BACKGROUND: Dexmedetomidine is a highly selective alpha-2 receptor agonist without any effect on the GABA receptor. It provides an excellent sedative and analgesic profile with few side effects. We report our experience with dexmedetomidine use during orthopaedic surgery under locoregional anaesthesia to ensure adequate sedation and optimal postoperative pain control. METHODS: In this retrospective analysis, we included 128 patients who underwent orthopaedic surgery between January 2019 and December 2021. All patients received the same local anaesthetic dose of 20 ml of ropivacaine 0.375% + mepivacaine 0.5% for axillary and supraclavicular block and 35 ml of ropivacaine 0.375% + mepivacaine 0.5% for triple nerve block (femoral, obturator and sciatic nerve). The cohort was divided into two groups based on sedation drugs used during surgery (dexmedetomidine, or group D, vs midazolam, or group M). All patients received postoperative 24-h analgesia consisting of 60 mg of ketorolac, 200 mg of tramadol and 4 mg of ondansetron. The primary outcome measured how many patients in the two groups required an analgesic rescue dose of pethidine and the time to first pethidine administration. To reduce confounding, we included patients in two groups with non-statistically different demo-anamnestic parameters and who received the same dose of intraoperative local anaesthetic and postoperative analgesia. RESULTS: The number of patients in group D who did not require a rescue dose of analgesia was significantly greater than in group M (49 vs 11, p < 0.001). Time-to-first postoperative opioid administration did not show a fundamental difference between the two groups under examination (523.75 ± 131.55 min vs 564 ± 117.84 min). Total opioid consumption was higher in the M group than in the D group (3529.8 ± 30.36 µg vs 1864.8 ± 31.59 µg, p 0.075), with a mean opioid consumption significantly higher in the M group than in the D group (26.26 ± 42.8 µg vs 69.21 ± 46.1 µg, p < 0.001): D group received 62.06% less opioid than M group. CONCLUSIONS: The continuous infusion of dexmedetomidine during orthopaedic surgery performed under locoregional anaesthesia has been shown to increase the analgesic effect of local anaesthetics and reduce the consumption of major opioids in the postoperative period. Dexmedetomidine offers a unique ability to supply sedation and analgesia without respiratory depression, having a wide safety margin and an excellent sedative capacity. It does not increase the rate of postoperative complications.

Preoperative Assessment and Management of Cardiovascular Risk in Patients Undergoing Non-Cardiac Surgery: Implementing a Systematic Stepwise Approach during the COVID-19 Pandemic Era.

Major adverse cardiac events, defined as death or myocardial infarction, are common causes of perioperative mortality and major morbidity in patients undergoing non-cardiac surgery. Reduction of perioperative cardiovascular risk in relation to non-cardiac surgery requires a stepwise patient evaluation that integrates clinical risk factors, functional status and the estimated stress of the planned surgical procedure. Major guidelines on preoperative cardiovascular risk assessment recommend to establish, firstly, the risk of surgery per se (low, moderate, high) and the related timing (elective vs. urgent/emergent), evaluate the presence of unstable cardiac conditions or a recent coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting), assess the functional capacity of the patient (usually expressed in metabolic equivalents), determine the value of non-invasive and/or invasive cardiovascular testing and then combine these data in estimating perioperative risk for major cardiac adverse events using validated scores (Revised Cardiac Risk Index (RCRI) or National Surgical Quality Improvement Program (NSQIP)). This stepwise approach has the potential to guide clinicians in determining which patients could benefit from cardiovascular therapy and/or coronary artery revascularization before non-cardiac surgery towards decreasing the incidence of perioperative morbidity and mortality. Finally, it should be highlighted that there is a need to implement specific strategies in the 2019 Coronavirus disease (COVID-19) pandemic to minimize the risk of transmission of COVID-19 infection during the preoperative risk assessment process.

The Effects of Visual Parabolic Motion on the Subjective Vertical and on Interception.

Observers typically present a strong bias in estimating the orientation of a visual bar when their body is tilted >60° in the roll plane and in the absence of visual background information. Known as the A-effect, this phenomenon likely results from the under-compensation of body tilt. Static visual cues can reduce such bias in the perceived vertical. Yet, it is unknown whether dynamic visual cues would be also effective. Here we presented projectile motions of a visual target along parabolic trajectories with different orientations relative to physical gravity. The aim of the experiment was twofold: First, we assessed whether the projectile motions could bias the estimation of the perceived orientation of a visual bar, measured with a classical subjective visual vertical (SVV) task. Second, we evaluated whether the ability to estimate time-to-contact of the visual target in an interception task was influenced by the orientation of these parabolic trajectories. Two groups of participants performed the experiment, either with their head and body tilted 90° along the roll plane or in an upright position. We found that the perceived orientation of the visual bar in the SVV task was affected by the orientation of the parabolic trajectories. This result was present in the tilted but not in the upright participants. In the interception task, the timing error increased linearly as a function of the orientation of the parabola. These results support the hypothesis that a gravity vector estimated from dynamic visual stimuli contributes to the subjective visual vertical.

Structural connectome and connectivity lateralization of the multimodal vestibular cortical network.

Unlike other sensory systems, the structural connectivity patterns of the human vestibular cortex remain a matter of debate. Based on their functional properties and hypothesized centrality within the vestibular network, the 'core' cortical regions of this network are thought to be areas in the posterior peri-sylvian cortex, in particular the retro-insula (previously named the posterior insular cortex-PIC), and the subregion OP2 of the parietal operculum. To study the vestibular network, structural connectivity matrices from n=974 healthy individuals drawn from the public Human Connectome Project (HCP) repository were estimated using multi-shell diffusion-weighted data followed by probabilistic tractography and spherical-deconvolution informed filtering of tractograms in combination with subject-specific grey-matter parcellations. Weighted graph-theoretical measures, modularity, and 'hubness' of the multimodal vestibular network were then estimated, and a structural lateralization index was defined in order to assess the difference in fiber density of homonym regions in the right and left hemisphere. Differences in connectivity patterns between OP2 and PIC were also estimated. We found that the bilateral intraparietal sulcus, PIC, and to a lesser degree OP2, are key 'hub' regions within the multimodal vestibular network. PIC and OP2 structural connectivity patterns were lateralized to the left hemisphere, while structural connectivity patterns of the posterior peri-sylvian supramarginal and superior temporal gyri were lateralized to the right hemisphere. These lateralization patterns were independent of handedness. We also found that the structural connectivity pattern of PIC is consistent with a key role of PIC in visuo-vestibular processing and that the structural connectivity pattern of OP2 is consistent with integration of mainly vestibular somato-sensory and motor information. These results suggest an analogy between PIC and the simian visual posterior sylvian (VPS) area and OP2 and the simian parieto-insular vestibular cortex (PIVC). Overall, these findings may provide novel insights to the current models of vestibular function, as well as to the understanding of the complexity and lateralized signs of vestibular syndromes.

Sensitivity of occipito-temporal cortex, premotor and Broca's areas to visible speech gestures in a familiar language.

When looking at a speaking person, the analysis of facial kinematics contributes to language discrimination and to the decoding of the time flow of visual speech. To disentangle these two factors, we investigated behavioural and fMRI responses to familiar and unfamiliar languages when observing speech gestures with natural or reversed kinematics. Twenty Italian volunteers viewed silent video-clips of speech shown as recorded (Forward, biological motion) or reversed in time (Backward, non-biological motion), in Italian (familiar language) or Arabic (non-familiar language). fMRI revealed that language (Italian/Arabic) and time-rendering (Forward/Backward) modulated distinct areas in the ventral occipito-temporal cortex, suggesting that visual speech analysis begins in this region, earlier than previously thought. Left premotor ventral (superior subdivision) and dorsal areas were preferentially activated with the familiar language independently of time-rendering, challenging the view that the role of these regions in speech processing is purely articulatory. The left premotor ventral region in the frontal operculum, thought to include part of the Broca's area, responded to the natural familiar language, consistent with the hypothesis of motor simulation of speech gestures.

Effects of visual motion consistent or inconsistent with gravity on postural sway.

Vision plays an important role in postural control, and visual perception of the gravity-defined vertical helps maintaining upright stance. In addition, the influence of the gravity field on objects' motion is known to provide a reference for motor and non-motor behavior. However, the role of dynamic visual cues related to gravity in the control of postural balance has been little investigated. In order to understand whether visual cues about gravitational acceleration are relevant for postural control, we assessed the relation between postural sway and visual motion congruent or incongruent with gravity acceleration. Postural sway of 44 healthy volunteers was recorded by means of force platforms while they watched virtual targets moving in different directions and with different accelerations. Small but significant differences emerged in sway parameters with respect to the characteristics of target motion. Namely, for vertically accelerated targets, gravitational motion (GM) was associated with smaller oscillations of the center of pressure than anti-GM. The present findings support the hypothesis that not only static, but also dynamic visual cues about direction and magnitude of the gravitational field are relevant for balance control during upright stance.

Path integration in 3D from visual motion cues: A human fMRI study.

While neural correlates of path integration on a yaw plane have been studied extensively, much less is known about path integration in three-dimensions (3D). Here we used fMRI during virtual navigation within tunnels in pseudo-3D. We found that the same visual motion stimuli are encoded differently in the brain depending on whether they represent displacements within the yaw plane or within the pitch plane. The yaw plane is more represented in the hippocampus while the pitch plane is more represented in the angular gyrus (AG) and in the posterior inferior temporal gyrus (pITG), known to be involved in 3D space encoding. In addition, a region in pITG, located just above the previous one, showed two different patterns with multi-voxel analysis, separately coding for the pitch and yaw planes. These results suggest that information encoded within pITG about the yaw plane may be exchanged with the hippocampus, while information about the pitch plane may be exchanged with the AG.

Processing of visual gravitational motion in the peri-sylvian cortex: Evidence from brain-damaged patients.

Rich behavioral evidence indicates that the brain estimates the visual direction and acceleration of gravity quite accurately, and the underlying mechanisms have begun to be unraveled. While the neuroanatomical substrates of gravity direction processing have been studied extensively in brain-damaged patients, to our knowledge no such study exists for the processing of visual gravitational motion. Here we asked 31 stroke patients to intercept a virtual ball moving along the vertical under either natural gravity or artificial reversed gravity. Twenty-seven of them also aligned a luminous bar to the vertical direction (subjective visual vertical, SVV). Using voxel-based lesion-symptom mapping as well as lesion subtraction analysis, we found that lesions mainly centered on the posterior insula are associated with greater deviations of SVV, consistent with several previous studies. Instead, lesions mainly centered on the parietal operculum decrease the ability to discriminate natural from unnatural gravitational acceleration with a timed motor response in the interception task. Both the posterior insula and the parietal operculum belong to the vestibular cortex, and presumably receive multisensory information about the gravity vector. We speculate that an internal model estimating the effects of gravity on visual objects is constructed by transforming the vestibular estimates of mechanical gravity, which are computed in the brainstem and cerebellum, into internalized estimates of virtual gravity, which are stored in the cortical vestibular network. The present lesion data suggest a specific role for the parietal operculum in detecting the mismatch between predictive signals from the internal model and the online visual signals.

Gravity in the Brain as a Reference for Space and Time Perception.

Moving and interacting with the environment require a reference for orientation and a scale for calibration in space and time. There is a wide variety of environmental clues and calibrated frames at different locales, but the reference of gravity is ubiquitous on Earth. The pull of gravity on static objects provides a plummet which, together with the horizontal plane, defines a three-dimensional Cartesian frame for visual images. On the other hand, the gravitational acceleration of falling objects can provide a time-stamp on events, because the motion duration of an object accelerated by gravity over a given path is fixed. Indeed, since ancient times, man has been using plumb bobs for spatial surveying, and water clocks or pendulum clocks for time keeping. Here we review behavioral evidence in favor of the hypothesis that the brain is endowed with mechanisms that exploit the presence of gravity to estimate the spatial orientation and the passage of time. Several visual and non-visual (vestibular, haptic, visceral) cues are merged to estimate the orientation of the visual vertical. However, the relative weight of each cue is not fixed, but depends on the specific task. Next, we show that an internal model of the effects of gravity is combined with multisensory signals to time the interception of falling objects, to time the passage through spatial landmarks during virtual navigation, to assess the duration of a gravitational motion, and to judge the naturalness of periodic motion under gravity.

Sound-evoked vestibular stimulation affects the anticipation of gravity effects during visual self-motion.

Humans anticipate the effects of gravity during visually simulated self-motion in the vertical direction. Here we report that an artificial vestibular stimulation consisting of short-tone bursts (STB) suppresses this anticipation. Participants pressed a button upon entering a tunnel during virtual-reality roller coaster rides in downward or forward directions. In different trials, we delivered STB, pulsed white noise (WN), or no sound (NO). In the control conditions (WN, NO), participants responded earlier during downward than forward motion irrespective of true kinematics, consistent with the a priori expectation that downward but not forward motion is accelerated by gravity. STB canceled the difference in response timing between the two directions, without affecting overall task performance. Thus, we argue that vestibular signals play a role in the anticipation of visible gravity effects during self-motion.

Filling gaps in visual motion for target capture.

A remarkable challenge our brain must face constantly when interacting with the environment is represented by ambiguous and, at times, even missing sensory information. This is particularly compelling for visual information, being the main sensory system we rely upon to gather cues about the external world. It is not uncommon, for example, that objects catching our attention may disappear temporarily from view, occluded by visual obstacles in the foreground. Nevertheless, we are often able to keep our gaze on them throughout the occlusion or even catch them on the fly in the face of the transient lack of visual motion information. This implies that the brain can fill the gaps of missing sensory information by extrapolating the object motion through the occlusion. In recent years, much experimental evidence has been accumulated that both perceptual and motor processes exploit visual motion extrapolation mechanisms. Moreover, neurophysiological and neuroimaging studies have identified brain regions potentially involved in the predictive representation of the occluded target motion. Within this framework, ocular pursuit and manual interceptive behavior have proven to be useful experimental models for investigating visual extrapolation mechanisms. Studies in these fields have pointed out that visual motion extrapolation processes depend on manifold information related to short-term memory representations of the target motion before the occlusion, as well as to longer term representations derived from previous experience with the environment. We will review recent oculomotor and manual interception literature to provide up-to-date views on the neurophysiological underpinnings of visual motion extrapolation.

Visual gravity cues in the interpretation of biological movements: neural correlates in humans.

Our visual system takes into account the effects of Earth gravity to interpret biological motion (BM), but the neural substrates of this process remain unclear. Here we measured functional magnetic resonance (fMRI) signals while participants viewed intact or scrambled stick-figure animations of walking, running, hopping, and skipping recorded at normal or reduced gravity. We found that regions sensitive to BM configuration in the occipito-temporal cortex (OTC) were more active for reduced than normal gravity but with intact stimuli only. Effective connectivity analysis suggests that predictive coding of gravity effects underlies BM interpretation. This process might be implemented by a family of snapshot neurons involved in action monitoring.

Unfamiliar Walking Movements Are Detected Early in the Visual Stream: An fMRI Study.

Two experiments investigated the network involved in the visual perception of walking. Video clips of forward and backward walk (real walk direction) were shown either as recorded, or reversed in time (rendering). In Experiment 1 (identification task), participants were asked to indicate whether or not the stimulus was time-reversed. In Experiment 2 (free-viewing), participants viewed the video clips passively. Identification accuracy was good with the more familiar scene, that is, when the visual walk was in the direction of the facing orientation, and at chance level in the opposite case. In both experiments, the temporo-occipital junction (TOJ) was activated more strongly by unfamiliar than familiar scenes. Only in Experiment 1 intraparietal, superior temporal, and inferior temporal regions were also activated. TOJ activation signals the detection in unfamiliar scenes of a mismatch between facing orientation and visual movement direction. We argue that TOJ response to a mismatch prevents the further processing of the visual input required to identify temporal inversions. When no mismatch is detected (familiar stimuli), TOJ would, instead, be involved in the kinematic analysis that makes such identification possible. The study demonstrates that unfamiliar walking movements are detected earlier than so far assumed along the visual movement processing stream.

Multisensory integration and internal models for sensing gravity effects in primates.

Gravity is crucial for spatial perception, postural equilibrium, and movement generation. The vestibular apparatus is the main sensory system involved in monitoring gravity. Hair cells in the vestibular maculae respond to gravitoinertial forces, but they cannot distinguish between linear accelerations and changes of head orientation relative to gravity. The brain deals with this sensory ambiguity (which can cause some lethal airplane accidents) by combining several cues with the otolith signals: angular velocity signals provided by the semicircular canals, proprioceptive signals from muscles and tendons, visceral signals related to gravity, and visual signals. In particular, vision provides both static and dynamic signals about body orientation relative to the vertical, but it poorly discriminates arbitrary accelerations of moving objects. However, we are able to visually detect the specific acceleration of gravity since early infancy. This ability depends on the fact that gravity effects are stored in brain regions which integrate visual, vestibular, and neck proprioceptive signals and combine this information with an internal model of gravity effects.

Anticipating the effects of visual gravity during simulated self-motion: estimates of time-to-passage along vertical and horizontal paths.

By simulating self-motion on a virtual rollercoaster, we investigated whether acceleration cued by the optic flow affected the estimate of time-to-passage (TTP) to a target. In particular, we studied the role of a visual acceleration (1 g = 9.8 m/s(2)) simulating the effects of gravity in the scene, by manipulating motion law (accelerated or decelerated at 1 g, constant speed) and motion orientation (vertical, horizontal). Thus, 1-g-accelerated motion in the downward direction or decelerated motion in the upward direction was congruent with the effects of visual gravity. We found that acceleration (positive or negative) is taken into account but is overestimated in module in the calculation of TTP, independently of orientation. In addition, participants signaled TTP earlier when the rollercoaster accelerated downward at 1 g (as during free fall), with respect to when the same acceleration occurred along the horizontal orientation. This time shift indicates an influence of the orientation relative to visual gravity on response timing that could be attributed to the anticipation of the effects of visual gravity on self-motion along the vertical, but not the horizontal orientation. Finally, precision in TTP estimates was higher during vertical fall than when traveling at constant speed along the vertical orientation, consistent with a higher noise in TTP estimates when the motion violates gravity constraints.