Suppressive antibiotic therapy for infectious endocarditis.

OBJECTIVES: Suppressive antibiotic therapy (SAT) is a long-term antibiotic strategy at times applied when an indicated surgical management of infective endocarditis (IE) is not possible. Our aim was to describe the characteristics and outcomes of patients having received SAT for IE. METHODS: We conducted a retrospective, observational study at Strasbourg University Hospital, France between January 2020 and May 2023. We reviewed all medical files taken into consideration at weekly meetings of the local Multidisciplinary Endocarditis Team (MET) during the study period. We included patients having received SAT following the MET evaluation. The primary endpoint was all-cause mortality at most recent follow-up. Secondary endpoints included all-cause mortality at 3 and 6 months, infection relapse, and tolerance issues attributed to SAT. RESULTS: The MET considered 251 patients during the study time, among whom 22 (9 %) had received SAT. Mean age was 77.2 ± 12.3 years. Patients were highly comorbid with a mean Charlson index score of 6.6 ± 2.5. Main indication for SAT was surgery indicated but not performed or an infected device not removed (20/22). Fourteen patients had prosthetic valve IE, including 9 TAVIs. Six patients had IE affecting cardiac implantable electronic devices. Staphylococcus aureus and enterococci were the main bacteria involved (6/22 each). Median follow-up time was 249 days (IQR 95-457 days). Mortality at most recent follow-up was 23 % (5/22). Three patients (14 %) presented tolerance issues attributed to SAT, and two patients suffered late infectious relapse. CONCLUSION: Mortality at most recent follow-up was low and tolerance issues were rare for patients under SAT, which might be a palliative approach to consider when optimal surgery or device removal is not possible.

Incidence and Time-to-Onset of Carbapenemase-Producing Enterobacterales (CPE) Infections in CPE Carriers: a Retrospective Cohort Study.

This study aimed to assess the proportion of carbapenemase-producing Enterobacterales (CPE) infections among all infectious episodes in CPE carriers, compare the time-to-onset of CPE infections with that of other infections, assess the mortality of patients with CPE infections, and identify risk factors for CPE infections in CPE carriers. A retrospective cohort study was performed over a 10-year period in our University Hospital, and 274 CPE carriers were identified. All infectious episodes within the first 6 months following the diagnosis of CPE rectal carriage were considered. Risk factor analysis for CPE infections in CPE carriers was performed by univariate and multivariate analyses. This study revealed an incidence of 24.1% (66/274) of CPE infection within 6 months of CPE carriage diagnosis. The 28-day all-cause mortality due to CPE infections was 25.7%. CPE infections represented 52.6% (70/133) of all infectious episodes in CPE carriers in the first 6 months following CPE carriage detection, and these significantly occurred earlier than non-CPE infections, with a median time of 15 versus 51 days, respectively (P < 0.01). Based on the multivariate analysis, prior neurological disease was the only risk factor associated with CPE infections in CPE carriers. CPE infections have an early onset, accounting for a large proportion of infections in CPE carriers, and are associated with high mortality. IMPORTANCE Carbapenemase-producing Enterobacterales (CPE) infections are emerging infections and may represent a therapeutic challenge, while effective antibiotic therapy is likely to be delayed. We aimed to assess the proportion of CPE infections in CPE carriers and to identify risk factors of CPE infections among this population that could guide empirical antibiotic therapy. We showed that CPE infections are frequent in CPE carriers, have an early onset after CPE carriage diagnosis, and represent a significant proportion of all infectious episodes in CPE carriers. No significant risk factors for CPE infections could be identified. Overall, this study suggests that empirical antibiotic treatment covering CPE might be initiated in CPE carriers at least in the first month after its diagnosis and in severe infections due to the high frequency and early occurrence of CPE infections in these patients.

Cerebral aspergillosis in the era of new antifungals: The CEREALS national cohort study Nationwide CEREbral Aspergillosis Lesional study (CEREALS).

BACKGROUND: Cerebral aspergillosis (CA) is a life-threatening disease for which diagnosis and management remain challenging. Detailed analyses from large cohorts are lacking. METHODS: We included 119 cases of proven (n = 54) or probable (n = 65) CA diagnosed between 2006 and 2018 at 20 French hospitals. Data were collected at baseline and during follow-up. Cerebral imaging was reviewed centrally by two neuroradiologists. RESULTS: The most frequent underlying conditions were hematological malignancy (40%) and solid organ transplantation (29%). Galactomannan was detected in the serum of 64% of patients. In 75% of cases, at least one of galactomannan, Aspergillus PCR, and ß-d-glucan was positive in the cerebrospinal fluid. Six-week mortality was 45%. Two distinct patterns of disease were identified according to presumed route of dissemination. Presumed haematogenous dissemination (n = 88) was associated with a higher frequency of impaired consciousness (64%), shorter time to diagnosis, the presence of multiple abscesses (70%), microangiopathy (52%), detection of serum galactomannan (69%) and Aspergillus PCR (68%), and higher six-week mortality (54%). By contrast, contiguous dissemination from the paranasal sinuses (n = 31) was associated with a higher frequency of cranial nerve palsy (65%), evidence of meningitis on cerebral imaging (83%), macrovascular lesions (61%), delayed diagnosis, and lower six-week mortality (30%). In multivariate analysis and in a risk prediction model, haematogenous dissemination, hematological malignancy and the detection of serum galactomannan were associated with higher six-week mortality. CONCLUSION: Distinguishing between hematogenous and contiguous dissemination patterns appears to be critical in the workup for CA, as they are associated with significant differences in clinical presentation and outcome.

Efficacy of abatacept in systemic lupus erythematosus: a retrospective analysis of 11 patients with refractory disease.

Objective The objective of this study was to assess the safety and efficacy of abatacept in patients with SLE refractory to conventional treatment in routine clinical practice. Methods This retrospective study included 11 SLE patients treated with abatacept for an active and refractory disease. The primary endpoint was the change in SLE Disease Activity Index (SLEDAI) score at six months. Response was defined as a decrease of SLEDAI ≥4 in a patient continuing abatacept. Results Indications of abatacept treatment were articular ( n=8), renal ( n=1) and cutaneous ( n=1) involvement and autoimmune thrombocytopenia ( n=1). Abatacept was discontinued before six months in two patients, because of adverse event ( n=1) and/or lupus flare ( n=2). The median SLEDAI decreased from 6 (2-20) to 4 (0-20) ( p=0.031). Decrease of SLEDAI ≥4 was observed in 6/11 patients (55%) and response to treatment according to the physician's judgement in 8/11 (73%) patients. Improvement of articular involvement was observed in 7/8 (87.5%) patients. Four adverse events were observed in three patients, but no severe infection occurred. Conclusion This study suggests some efficacy of abatacept in patients with refractory disease in routine clinical practice, particularly in the case of articular manifestations, with an acceptable safety profile. These data support conducting new controlled trials of abatacept in SLE patients.

Effect of object width on precision grip force and finger posture.

This study aimed to define the effect of object width on spontaneous grasp. Participants held objects of various masses (0.75 to 2.25 kg) and widths (3.5 to 9.5 cm) between thumb and index finger. Grip force, maximal grip force and corresponding finger postures were recorded using an embedded force sensor and an optoelectronic system, respectively. Results showed that index finger joints varied to accommodate the object width, whereas thumb posture remained constant across conditions. For a given object mass, grip force increased as a function of object width, although this result is not dictated by the laws of mechanics. Because maximal grip force also increased with object width, we hypothesise that participants maintain a constant ratio between grip force and their maximal grip force at each given width. Altogether we conclude that when the task consists in manipulating objects/tools, the optimal width is different than when maximal force exertions are required.

Grip force safety margin in rock climbers.

When holding an object, grip force (Gf) is larger than the smallest force needed to prevent slipping (Gmin). The unnecessary grip force is termed safety margin (SM = Gf - Gmin). Because some hand injuries in rock climbing are largely encouraged by excessive grip force, safety margin was examined in a set of expert climbers, and compared to a set of non-climbers. Subjects were asked to hold a heavy or a light object during either a short or a long duration. We focused on the relative safety margin (RSM = 100 x SM/Gmin) adopted at the initiation of each trial. With the heavy object, climbers and non-climbers had similar RSMs (155 versus 148 %). With the light object, higher RSMs were reached, albeit smaller in climbers as compared to non-climbers (232 versus 386 %). Surprisingly, all subjects exhibited larger RSMs at the initiation of a long trial (246 versus 215 %). We conclude that expertise in rock climbing is not accompanied by key changes in RSMs that increase the likelihood of hand injuries. On the other hand, the fact that grip force is so crudely optimized at large load, especially when planning to sustain a hold, does promote the risk of hand injury in climbers.

The contribution of non-digital afferent signals to grip force adjustments evoked by brisk unloading of the arm or the held object.

OBJECTIVE: Earlier studies suggest that grip force adjustments evoked by mechanical perturbations result more from cutaneous signals from the fingertips, than from afferent signals from the supporting limb. Generally an increase in tangential load at the fingertips induces an increase in grip force, whereas a decrease in load induces the opposite reaction. Some data suggest that prior knowledge and experience influences the magnitude of grip force adjustments. METHODS: This study examines the relative contribution of digital and arm afferent signals in the context of brisk involuntary upward flexions obtained either by unloading the arm (ARM) or the held object (OBJECT). Following the perturbation, the tangential load at the fingertips increased in ARM, but decreased in OBJECT. A subsidiary goal was to compare the performance of naive subjects with the performance of trained and informed subjects. RESULTS: When the perturbation was completely unexpected, grip force increased sharply after OBJECT and ARM unloading. By contrast, when subjects had prior knowledge and experience with the upcoming perturbation, grip responses were clearly differentiated; grip force increased after ARM, but decreased after OBJECT. CONCLUSIONS: These results challenge the view that cutaneous signals of the fingertips are the driving signals of grip force responses. Instead, afferent signals from the flexed arm would account well for the lack of difference between grip force responses in ARM and OBJECT under unpredictable conditions. These data provide clear evidence that prior knowledge and experience influences reactive grip force control, since subjects became able to repress unnecessary grip force modulation in OBJECT. SIGNIFICANCE: These data have implications for understanding the initiation and the modulation of grip force adjustments.

How dependent are grip force and arm actions during holding an object?

In everyday life, when manipulating objects, arm actions and precision grip force are tightly coupled by the central nervous system. To investigate the extent of this neural coupling, 11 subjects were asked to perform tasks that encourage either the coupling (Task 1) or the dissociation (Task 2 and 3) of grip force and arm actions. During Task 1, subjects held a grasping device, with an extra load suspended underneath by a string. Then, using the other hand, subjects were asked to lift or release the suspended load, while maintaining unaffected the posture of the grasping arm. During Task 2, while holding the device, subjects received similar instructions, but this time the extra load was suspended underneath the forearm. During Task 3, subjects were explicitly asked to modulate their grip force without moving the arm. In Task 1, grip force changed in parallel with, or slightly ahead of, changes in load, which is consistent with the view of a feedforward mechanism making grip force largely subordinate to ongoing arm actions. In Task 2, even though subjects had no obvious reasons to modulate their force (i.e. the load of the device was constant) they did so, with a number of features that resemble performance in Task 1. In Task 3, as expected, voluntary modulations in grip force had no effect on arm actions. It is concluded that the neural coupling between arm actions and grip force (1) can possibly lead to clumsy reactions, (2) depends on the focal action, and (3) is only unidirectional.

Stride variability in human gait: the effect of stride frequency and stride length.

This study focused on spatial and temporal variability of the stride in human gait. We determined the role of stride frequency (F) and stride length (L) on those parameters. Eight healthy subjects walked on a treadmill using 25 different FL combinations (0.95

Structure of motor variability in marginally redundant multifinger force production tasks.

The framework of the uncontrolled manifold hypothesis (UCM hypothesis) was applied to the analysis of the structure of finger force variability during oscillatory force production tasks. Subjects produced cycles of force with one, two (index and middle), or three (index, middle, and ring) fingers acting in parallel against force sensors mounted inside a small frame. The frame could be placed on the top of a table (stable conditions) or on a 4-mm-wide supporting surface (unstable conditions). Subjects were less variable when they used two fingers than when using one finger; adding the third finger did not change indices of variability of the performance. Components of finger force variance that did (VUN) or did not (VCOMP) change the value of a particular functional variable were computed for two control hypotheses: (1) at each time, the subjects tried to stabilize the total value of force (force-control); and (2), at each time, the subjects tried to stabilize the total moment produced with respect to an axis parallel to the hand/forearm (moment-control). Most subjects showed selective stabilization of moment and destabilization of force throughout most of the force cycle, in both stable and unstable conditions. The shapes of VUN and VCOMP suggested a possibility of selective compensation of timing errors across fingers within force cycles. One subject showed different relations between VUN and VCOMP, suggesting that these relations did in fact reflect particular central strategies of solving the tasks. The UCM method is applicable to force production tasks. It allows the comparison of control hypotheses in a quantitative way and unveils central strategies of control of redundant motor systems. Within this approach, redundancy (rather, abundance) is not a problem but an inherent part of a solution for natural motor tasks.

Bilateral multifinger deficits in symmetric key-pressing tasks.

Maximal voluntary force during simultaneous bilateral and multifinger exertion has been shown to be smaller than the sum of unilateral or single-finger exertions. The goal of this study was to study the force deficit associated with bilateral multifinger tasks. Eight normal college students performed four types of maximal isometric key-pressing tasks: (1) unilateral single-finger, (2) bilateral single-finger, (3) unilateral multifinger, and (4) bilateral multifinger. Forces produced by the index (I), middle (M), ring (R), and little (L) fingers and surface electromyography (EMG) of extrinsic finger flexors were recorded. Multifinger deficit (MFD) was defined as the percentage difference between the force (or EMG) produced by a set of fingers and the sum of the forces (or EMGs) produced by the individual fingers in their unilateral single-finger tasks. Bilateral deficit (BLD) was defined as the percentage difference between the force (or EMG) produced by a set of fingers and the sum of the forces (or EMGs) produced by the finger subsets of the left and right hands. Significant BLD and MFD in force and EMG were found for all bilateral multifinger tasks and some of the bilateral single-finger tasks. Both BLD and MFD were dependent on the number of fingers involved. BLD ranged from 3% to 22.7% for force and from 8.9% to 31.0% for EMG, including bilateral single-finger and bilateral multifinger tasks. MFDs in force during bilateral I-, IM-, IMR-, and IMRL-finger tasks were 13.2%, 37.8%, 53.2%, 52.3%, respectively; and the corresponding MFDs in EMG were 11.7%, 51.3%, 67.6%, and 71.0%, respectively. BLD and MFD in EMG were found to vary in parallel with the corresponding force deficits. It was suggested that the neural ceiling effect remains the most plausible mechanism underlying the observed deficits. The central nervous system is unable to activate maximally a large number of muscle groups at the same time during tasks involving multiple body parts. During bilateral multifinger tasks, the ceiling effect may be organized hierarchically: (1) a certain limited neural drive is shared bilaterally, leading to a BLD; (2) at each hand, a certain limited neural drive is shared by multiple fingers, leading to MFD within a hand; (3) the deficits at bilateral and unilateral multifinger levels are cumulative during bilateral multifinger tasks, leading to a higher deficit associated with the tasks.

The effect of a fatiguing exercise by the index finger on single- and multi-finger force production tasks.

We studied the effects of fatigue, induced by a 60-s maximal isometric force production with the index finger, on multi-finger coordination and force production by the other fingers of the hand. Finger forces were measured during single- and multi-finger maximal voluntary force production (MVC) at two sites, the middle of the distal or the middle of the proximal phalanges. Two fatiguing exercises involving force production by the index finger were used, one at the distal phalanx and the other at the proximal phalanx. The MVC of the index finger dropped by about 33% when it was produced at the site involved in the fatiguing exercise. In addition, large transfer effects of fatigue were observed across sites of force application and across fingers. Force deficit increased under fatigue, especially due to a drop in the recruitment of the index finger. Under fatigue, the index finger was less enslaved during force production by other fingers. During multi-finger tasks, the percentage of total force produced by the index finger was significantly reduced after the fatiguing exercise. The principle of minimization of secondary moments was violated under fatigue. We suggest that the most impaired (fatigued) finger shows less interaction with other fingers or, in other words, is being progressively removed from the multi-finger synergy. Some of the observed changes in finger coordination suggest effects of fatigue at a central (neural) level.

The effect of expertise in gymnastics on postural control.

The goal of this paper was (1) to investigate if gymnasts have a more stable standing posture than experts in other sports, and (2) to determine how much gymnasts are affected by the removal of vision in different postural tasks. Six expert gymnasts and six experts in other non-gymnastic sports were asked to maintain balance in three standing postures of increasing difficulty: bipedal, unipedal, and unipedal + unstable support (i.e. 7 cm thick foam surface). Each posture was tested successively with and without vision. Based on the displacement of the center of pressure (range and mean average speed), the results showed that when visual cues were available, postural sway increased with the difficulty of the task, but both groups had comparable performance in all the tasks. When vision was removed, although both groups demonstrated larger postural sway in the unipedal tasks, this effect was less accentuated for the gymnasts. We concluded that gymnasts are able to use the remaining sensory modalities to compensate for the lack of vision in unstable postures.

Bilateral deficit and symmetry in finger force production during two-hand multifinger tasks.

A comprehensive study of patterns of finger forces during one-hand and two-hand multifinger maximal force production trials was performed with particular emphasis on differences between tasks involving symmetrical and asymmetrical finger groups (symmetrical and asymmetrical tasks). Twelve healthy right-handed subjects performed maximal voluntary force production tasks with different finger combinations. Force deficit (FD) for a finger group within a hand was defined as a drop in peak force in a multifinger task as compared to the sum of individual finger peak forces in single-finger tasks. FD showed a dependence on both the number of fingers within the hand and the number of fingers in the other hand. An additional drop in peak finger forces was seen in two-hand tests (bilateral deficit, BD). BD summed over two hands was independent of the number of fingers involved in the two-hand tasks, but dependent on the distribution of fingers between the two hands. BD for a hand was larger for tasks involving fewer fingers within the hand and more fingers in the other hand. It was higher for asymmetrical tasks than for symmetrical tasks. The difference between asymmetrical and symmetrical tasks was due to the different behavior of asymmetrically involved fingers. FD was larger for asymmetrical master (explicitly involved) fingers, while forces produced involuntarily by asymmetrical slave (explicitly non-involved) fingers were larger. These differences brought down the total moment produced by both hands in the frontal plane. FD and BD are phenomena of different origin whose effects sum up. The observations have led to further development of a previously proposed double-representation, mirror-image (DoReMi) hypothesis and refinement of the neural network underlying the two-hand finger interaction.

Control of locomotion in expert gymnasts in the absence of vision.

The main aim of this study was to determine how gymnasts are affected by the removal of vision when executing simple moves. A secondary aim was to establish whether crucial sensory cues exist for blindfolded gymnasts. Eight expert gymnasts were asked to maintain a straight displacement during three types of blindfolded locomotion: walking, steering a wheelchair and verbally ordering a second person pushing their wheelchair. In the first two conditions, active displacement made proprioceptive cues available to update the body trajectory. In the last condition, however, proprioceptive cues were greatly reduced, since the gymnasts displaced passively. The performance of the gymnasts was compared to that of eight experts in other non-gymnastic sports (control group). The results showed that the participants veered in all conditions. However, except in the verbal condition, the gymnasts departed less from linearity than the controls. We conclude that: (1) even for a simple motor task, gymnasts' performance is altered by eliminating vision; (2) compared with other sportsmen and women, gymnasts are better able to deal with the absence of vision when proprioceptive cues are available. These findings suggest two possible explanations: (1) gymnasts are more able to 'pick up' crucial information and (2) a gymnast's proprioceptive system is more sensitive.

Adaptation of neuromuscular synergies during intentional constraints of space-time relationships in human gait.

Tight frequency-to-amplitude relationships are observed in spontaneous human steady gait. They can be modified, if required; that flexibility forms a fundamental basis of the intentional adaptive capabilities of locomotion. In the present experiments, the processes underlying that flexibility were investigated at both the level of joint kinematics and the level of neuromuscular synergies. Subjects (N = 4) walked at the same speed either with a preferred or a nonpreferred frequency-to-amplitude relationship (i.e., constrained, short steps at a high frequency [COS condition] or constrained, long steps at a low frequency [COL condition]); their swing and stance phases were separately analyzed. In the COS condition, increases in EMG activity were specifically required during the swing phase. In the COL condition, several muscles required increases in EMG activity during the stance phase, but decreases of the hamstring muscles were needed during the swing phase. Whereas, in preferred walking, modification of the frequency affects the EMG patterns globally (the gain increasing with the frequency in both the stance and swing phases), the present results show that changing the frequency in a constrained manner either affects the swing phase specifically or affects both phases, but in the opposite direction. That finding indicates that a separate control is needed in both the swing and the stance phases.

The effect of fatigue on multifinger co-ordination in force production tasks in humans.

1. This study investigated the effects of fatigue, induced by production of maximal isometric force for 60 s with four fingers, upon indices of multifinger co-ordination. 2. Measurements of individual finger forces were performed during single- and multifinger maximal force production (maximal voluntary contraction, MVC) for two sites of force application, the middle of the distal or the middle of the proximal phalanxes. Two fatiguing exercises were used, involving force production at the distal phalanxes and at the proximal phalanxes. Fourteen subjects were tested. 3. The total force in four-finger tasks dropped by about 43 % when it was produced at the site involved in the fatiguing exercise. During force production at the other site, MVC dropped by 23 %. During single-finger MVC tests, force drop with fatigue was similar across all four fingers (about -25 % of their corresponding MVCs). 4. Force production by one finger was accompanied by involuntary force production by other fingers (enslaving). Enslaving remained unchanged by fatigue when measured during force generation at the site involved in the fatiguing exercise, but increased during force production at the other site. 5. The total MVC of four fingers acting in parallel was smaller than the sum of the MVCs of these fingers in single-finger tasks (force deficit). The force deficit increased with fatigue. Force-sharing patterns during four-finger tasks showed only minor changes under fatigue. 6. These results indicate that the effects of fatigue were not limited to changes in the force-generating capabilities of the muscles. In particular, fatigue could lead to a reorganisation at a neural level that defines commands to individual fingers.

Veering in human locomotion: the role of the effectors.

Without visual information, human subjects are not able to maintain displacement in a straight line. This tendency is called veering. The goal of this paper was to investigate the origin of veering in a population of subjects who were homotropic during walking (i.e. veering consistently in the same direction on repeated trials). Three types of locomotion were compared, each one required a specific set of effectors: (i) walking (LEG); (ii) propelling on a wheelchair (ARM) and (iii) verbally ordering a second person pushing the wheelchair (VERB). After 15 m displacement, all subjects (n = 8) exhibited large deviations from the initial direction (2.5 m in LEG, 3.2 m in ARM and 4 m in VERB). We also observed that all participants were homotropic in ARM, but only half of them continued to veer in the same direction than in LEG. By contrast in VERB, deviations occurred randomly. We concluded that systematic deviations occurring in two-limb displacements originate from a peripheral mechanism (slight different properties of the right and left limbs) rather than a central mechanism (systematic bias in the perceived body trajectory).