A method for calculating fall risk parameters from discrete stride time series regardless of sensor placement.

BACKGROUND: To complement traditional clinical fall risk assessments, research is oriented towards adding real-life gait-related fall risk parameters (FRP) using inertial sensors fixed to a specific body position. While fixing the sensor position can facilitate data processing, it can reduce user compliance. A newly proposed step detection method, Smartstep, has been proven to be robust against sensor position and real-life challenges. Moreover, FRP based on step variability calculated from stride times (Standard deviation (SD), Coefficient of Variance (Cov), fractal exponent, and sample entropy of stride duration) proved to be useful to prospectively predict the fall risk. RESEARCH QUESTIONS: To evaluate whether Smartstep is convenient for calculating FRP from different sensor placements. METHODS: 29 elderly performed a 6-minute walking test with IMU placed on the waist and the wrist. FRP were computed from step-time estimated from Smartstep and compared to those obtained from foot-mounted inertial sensors: precision and recall of the step detection, Root mean square error (RMSE) and Intraclass Correlation Coefficient (ICC) of stride durations, and limits of agreement of FRP. RESULTS: The step detection precision and recall were respectively 99.5% and 95.9% for the waist position, and 99.4% and 95.7% for the wrist position. The ICC and RMSE of stride duration were 0.91 and 54 ms respectively for both the waist and the hand position. The limits of agreement of Cov, SD, fractal exponent, and sample entropy of stride duration are respectively 2.15%, 25 ms, 0.3, 0.5 for the waist and 1.6%, 16 ms, 0.23, 0.4 for the hand. SIGNIFICANCE: Robust against the elderly's gait and different body locations, especially the wrist, this method can open doors toward ambulatory measurements of steps, and calculation of different discrete stride-related falling risk indicators.

The Potential Role of Wearable Inertial Sensors in Laboring Women with Walking Epidural Analgesia.

There is a growing interest in wearable inertial sensors to monitor and analyze the movements of pregnant women. The noninvasive and discrete nature of these sensors, integrated into devices accumulating large datasets, offers a unique opportunity to study the dynamic changes in movement patterns during the rapid physical transformations induced by pregnancy. However, the final cut of the third trimester of pregnancy, particularly the first stage of labor up to delivery, remains underexplored. The growing popularity of "walking epidural", a neuraxial analgesia method allowing motor function preservation, ambulation, and free movement throughout labor and during delivery, opens new opportunities to study the biomechanics of labor using inertial sensors. Critical research gaps exist in parturient fall prediction and detection during walking epidural and understanding pain dynamics during labor, particularly in the presence of pelvic girdle pain. The analysis of fetal descent, upright positions, and their relationship with dynamic pelvic movements facilitated by walking during labor is another area where inertial sensors can play an interesting role. Moreover, as contemporary obstetrics advocate for less restricted or non-restricted movements during labor, the role of inertial sensors in objectively measuring the quantity and quality of women's movements becomes increasingly important. This includes studying the impact of epidural analgesia on maternal mobility, walking patterns, and associated obstetrical outcomes. In this paper, the potential use of wearable inertial sensors for gait analysis in the first stage of labor is discussed.

Oral fluorescein angiography in the diagnosis of paediatric optic nerve abnormalities.

OBJECTIVE: FFA is a well-established investigation for the diagnosis of optic nerve abnormalities, requiring an intravenous cannula and extended imaging acquisition time. Cannulation can present a challenge in paediatric patients and whilst oral FFA has been used for decades, it has been limited by imaging technology and unconfirmed image acquisition timings. For years, we have used a modern ultra-widefield retinal camera, and established imaging time-points to demonstrate dynamic optic nerve head changes upon ingestion of fluorescein and collected a database of oFFA images for various presentations. METHODS: Using an established protocol, optic nerve colour images were obtained, followed by oral administration of fluorescein dye. The optic nerves are then imaged at established intervals. An interpretation of oFFA tutorial was delivered to consultant ophthalmologists and trainees. Subsequently, these groups were assessed using a series of fifteen cases with the sensitivity and specificity of the test determined. RESULTS: Our study presents a series of images and descriptions for common optic nerve abnormalities in paediatric populations. In the interpretation part of the study, overall sensitivity of 76.8% in the consultant group vs 63.3% in the combined consultant + trainees and specificity of 87.5% vs 68.4% in the combined group. CONCLUSIONS: This is the first study that describes characteristic features of several common, and serious, optic nerve abnormalities specifically for oFFA interpretation in a paediatric population. It also highlights the rapid accumulation of oFFA interpretation skills in non-specialist consultant and trainee ophthalmologists such as to obtain a high diagnostic accuracy with high sensitivity and specificity.

Agreement between a markerless and a marker-based motion capture systems for balance related quantities.

Balance studies usually focus on quantities describing the global body motion. Assessing such quantities using classical marker-based approach can be tedious and modify the participant's behaviour. The recent development of markerless motion capture methods could bypass the issues related to the use of markers. This work compared dynamic balance related quantities obtained with markers and videos. Sixteen young healthy participants performed four different motor tasks: walking at self-selected speed, balance loss, walking on a narrow beam and countermovement jumps. Their movements were recorded simultaneously by marker-based and markerless motion capture systems. Videos were processed using a commercial markerless pose estimation software, Theia3D. The centre of mass position (CoM) was computed, and the associated extrapolated centre of mass position (XCoM) and whole-body angular momentum (WBAM) were derived. Bland-Altman analysis was performed and root mean square difference (RMSD) and coefficient of correlation were computed to compare the results obtained with marker-based and markerless methods. Bias remained of the magnitude of a few mm for CoM and XCoM positions, and RMSD of CoM and XCoM was around 1 cm. RMSD of the WBAM was less than 10 % of the total amplitude in any direction, and bias was less than 1 %. Results suggest that outcomes of balance studies will be similar whether marker-based or markerless motion capture system are used. Nevertheless, one should be careful when assessing dynamic movements such as jumping, as they displayed the biggest differences (both bias and RMSD), although it is unclear whether these differences are due to errors in markerless or marker-based motion capture system.

"MeiQuant": An Integrated Tool for Analyzing Meiotic Prophase I Spread Images.

Immunocytochemical analysis of meiotic proteins on mouse chromosome spreads is one method of choice to study prophase I chromosome organization and homologous recombination. In recent decades, the development of microscopic approaches led to the production of a large number of images that monitor fluorescent proteins, defined as fluorescent objects, and a major challenge facing the community is the deep analysis of these fluorescent objects (measurement of object length, intensity, distance between objects, as well as foci identification, counting, and colocalization). We propose a set of tools designed from the macro language of the widely used image analysis software ImageJ (Schindelin et al., Nat Methods 9: 676-682, 2012), embedded in the "MeiQuant" macro, which are specifically designed for analyzing objects in the field of meiosis. Our aim is to propose a unified evolutive common tool for image analysis, with a specific focus on mouse prophase I meiotic events.

Anatomical registration of intracranial electrodes. Robust model-based localization and deformable smooth brain-shift compensation methods.

BACKGROUND: Intracranial electrodes are typically localized from post-implantation CT artifacts. Automatic algorithms localizing low signal-to-noise ratio artifacts and high-density electrode arrays are missing. Additionally, implantation of grids/strips introduces brain deformations, resulting in registration errors when fusing post-implantation CT and pre-implantation MR images. Brain-shift compensation methods project electrode coordinates to cortex, but either fail to produce smooth solutions or do not account for brain deformations. NEW METHODS: We first introduce GridFit, a model-based fitting approach that simultaneously localizes all electrodes' CT artifacts in grids, strips, or depth arrays. Second, we present CEPA, a brain-shift compensation algorithm combining orthogonal-based projections, spring-mesh models, and spatial regularization constraints. RESULTS: We tested GridFit on ∼6000 simulated scenarios. The localization of CT artifacts showed robust performance under difficult scenarios, such as noise, overlaps, and high-density implants (<1 mm errors). Validation with data from 20 challenging patients showed 99% accurate localization of the electrodes (3160/3192). We tested CEPA brain-shift compensation with data from 15 patients. Projections accounted for simple mechanical deformation principles with < 0.4 mm errors. The inter-electrode distances smoothly changed across neighbor electrodes, while changes in inter-electrode distances linearly increased with projection distance. COMPARISON WITH EXISTING METHODS: GridFit succeeded in difficult scenarios that challenged available methods and outperformed visual localization by preserving the inter-electrode distance. CEPA registration errors were smaller than those obtained for well-established alternatives. Additionally, modeling resting-state high-frequency activity in five patients further supported CEPA. CONCLUSION: GridFit and CEPA are versatile tools for registering intracranial electrode coordinates, providing highly accurate results even in the most challenging implantation scenarios. The methods are implemented in the iElectrodes open-source toolbox.

Embryology of the vertebral artery and variants of the adult.

The vertebral arteries represent in the adult the main blood supply of the posterior cranial fossa, even if they appear relatively late during the embryological life. We reviewed all the most important steps of the vertebral artery's embryological development and the most common variants that can occur in the adult. The aim of this review is to summarize the main events of the development of this artery and to give an embryological explication for the most common variants of this artery.

Beyond the kidney biopsy: genomic approach to undetermined kidney diseases.

Background: According to data from large national registries, almost 20%-25% of patients with end-stage kidney disease have an undetermined kidney disease (UKD). Recent data have shown that monogenic disease-causing variants are under-diagnosed. We performed exome sequencing (ES) on UKD patients in our center to improve the diagnosis rate. Methods: ES was proposed in routine practice for patients with UKD including kidney biopsy from January 2019 to December 2021. Mutations were detected using a targeted bioinformatic customized kidney gene panel (675 genes). The pathogenicity was assessed using American College of Medical Genetics guidelines. Results: We included 230 adult patients, median age 47.5 years. Consanguinity was reported by 25 patients. A family history of kidney disease was documented in 115 patients (50%). Kidney biopsies were either inconclusive in 69 patients (30.1%) or impossible in 71 (30.9%). We detected 28 monogenic renal disorders in 75 (32.6%) patients. Collagenopathies was the most common genetic kidney diagnosis (46.7%), with COL4A3 and COL4A4 accounting for 80% of these diagnoses. Tubulopathies (16%) and ciliopathies (14.7%) yielded, respectively, the second and third genetic kidney diagnosis category and UMOD-associated nephropathy as the main genetic findings for tubulopathies (7/11). Ten of the 22 patients having ES "first" eventually received a positive diagnosis, thereby avoiding 11 biopsies. Among the 44 patients with glomerular, tubulo-interstitial or vascular nephropathy, 13 (29.5%) were phenocopies. The diagnostic yield of ES was higher in female patients (P = .02) and in patients with a family history of kidney disease (P < .0001), reaching 56.8% when the patient had both first- and second-degree family history of renal disease. Conclusion: Genetic diagnosis has provided new clinical insights by clarifying or reclassifying kidney disease etiology in over a third of UKD patients. Exome "first" may have a significant positive diagnostic yield, thus avoiding invasive kidney biopsy; moreover, the diagnostic yield remains elevated even when biopsy is impossible or inconclusive. ES provides a clinical benefit for routine nephrological healthcare in patients with UKD.

Measuring objective physical activity in people with chronic low back pain using accelerometers: a scoping review.

Purpose: Accelerometers can be used to objectively measure physical activity. They could be offered to people with chronic low back pain (CLBP) who are encouraged to maintain an active lifestyle. The aim of this study was to examine the use of accelerometers in studies of people with CLBP and to synthesize the main results regarding the measurement of objective physical activity. Methods: A scoping review was conducted following Arksey and O'Malley's framework. Relevant studies were collected from 4 electronic databases (PubMed, Embase, CINHAL, Web of Science) between January 2000 and July 2023. Two reviewers independently screened all studies and extracted data. Results: 40 publications out of 810 citations were included for analysis. The use of accelerometers in people with CLBP differed across studies; the duration of measurement, physical activity outcomes and models varied, and several limitations of accelerometry were reported. The main results of objective physical activity measures varied and were sometimes contradictory. Thus, they question the validity of measurement methods and provide the opportunity to discuss the objective physical activity of people with CLBP. Conclusions: Accelerometers have the potential to monitor physical performance in people with CLBP; however, important technical limitations must be overcome.

Association of Prospective Falls in Older People With Ubiquitous Step-Based Fall Risk Parameters Calculated From Ambulatory Inertial Signals: Secondary Data Analysis.

Background: In recent years, researchers have been advocating for the integration of ambulatory gait monitoring as a complementary approach to traditional fall risk assessments. However, current research relies on dedicated inertial sensors that are fixed on a specific body part. This limitation impacts the acceptance and adoption of such devices. Objective: Our study objective is twofold: (1) to propose a set of step-based fall risk parameters that can be obtained independently of the sensor placement by using a ubiquitous step detection method and (2) to evaluate their association with prospective falls. Methods: A reanalysis was conducted on the 1-week ambulatory inertial data from the StandingTall study, which was originally described by Delbaere et al. The data were from 301 community-dwelling older people and contained fall occurrences over a 12-month follow-up period. Using the ubiquitous and robust step detection method Smartstep, which is agnostic to sensor placement, a range of step-based fall risk parameters can be calculated based on walking bouts of 200 steps. These parameters are known to describe different dimensions of gait (ie, variability, complexity, intensity, and quantity). First, the correlation between parameters was studied. Then, the number of parameters was reduced through stepwise backward elimination. Finally, the association of parameters with prospective falls was assessed through a negative binomial regression model using the area under the curve metric. Results: The built model had an area under the curve of 0.69, which is comparable to models exclusively built on fixed sensor placement. A higher fall risk was noted with higher gait variability (coefficient of variance of stride time), intensity (cadence), and quantity (number of steps) and lower gait complexity (sample entropy and fractal exponent). Conclusions: These findings highlight the potential of our method for comprehensive and accurate fall risk assessments, independent of sensor placement. This approach has promising implications for ambulatory gait monitoring and fall risk monitoring using consumer-grade devices.

Diagnosis of Kidney Diseases of Unknown Etiology Through Biopsy-Genetic Analysis.

Introduction: Previous studies have suggested that genetic kidney diseases in adults are often overlooked, representing up to 10% of all cases of chronic kidney disease (CKD). We present data obtained from exome sequencing (ES) analysis of patients with biopsy-proven undetermined kidney disease (UKD). Methods: ES was proposed during routine clinical care in patients with UKD from January 2020 to December 2021. We used in silico custom kidney genes panel analysis to detect pathological variations using American College of Medical Genetics guidelines in 52 patients with biopsy-proven UKD with histological finding reassessment. Results: We detected 12 monogenic renal disorders in 21 (40.4%) patients. The most common diagnoses were collagenopathies (8/21,38.1%), COL4A3 and COL4A4 accounting for 80% of these diagnoses, and ciliopathies (5/21, 23.8%). The diagnostic yield of ES was higher in female patients and patients with a family history of kidney disease (57.1% and 71%, respectively). Clinical nephropathy categories matched with the final genetic diagnoses in 72.7% of cases, whereas histological renal lesions matched with the final diagnoses in 92.3% of cases. The genetics diagnoses and histopathological findings were in complete agreement for both glomerular and tubulointerstitial cases. Interstitial inflammation without tubulitis was only observed in tubulopathies or ciliopathies. Isolated CKD, CKD with proteinuria or hematuria, and isolated proteinuria or hematuria yielded the highest diagnostic yields (54.6%, 52.6%, and 42.9%, respectively). Conclusion: ES done in patients with biopsy-proven UKD should be considered as a first-line tool for CKD patients with a family history of kidney disease. Combination of ES and kidney biopsy may have major impacts on kidney disease ontology.

A Review of the Popular Uses, Anatomical, Chemical, and Biological Aspects of Kalanchoe (Crassulaceae): A Genus of Plants Known as "Miracle Leaf".

Species of the genus Kalanchoe have a long history of therapeutic use in ethnomedicine linked to their remarkable healing properties. Several species have chemical and anatomical similarities, often leading to confusion when they are used in folk medicine. This review aims to provide an overview and discussion of the reported traditional uses, botanical aspects, chemical constituents, and pharmacological potential of the Kalanchoe species. Published scientific materials were collected from the PubMed and SciFinder databases without restriction regarding the year of publication through April 2023. Ethnopharmacological knowledge suggests that these species have been used to treat infections, inflammation, injuries, and other disorders. Typically, all parts of the plant are used for medicinal purposes either as crude extract or juice. Botanical evaluation can clarify species differentiation and can enable correct identification and validation of the scientific data. Flavonoids are the most common classes of secondary metabolites identified from Kalanchoe species and can be correlated with some biological studies (antioxidant, anti-inflammatory, and antimicrobial potential). This review summarizes several topics related to the Kalanchoe genus, supporting future studies regarding other unexplored research areas. The need to conduct further studies to confirm the popular uses and biological activities of bioactive compounds is also highlighted.

Overexpression of Eimeria tenella Rhoptry Kinase 2 Induces Early Production of Schizonts.

Eimeria tenella is an obligate intracellular parasite responsible for avian coccidiosis. Like other apicomplexan parasites, such as Toxoplasma gondii, cell invasion and intracellular development rely on apical organelle content discharge, named micronemes and rhoptries. Some rhoptry (ROP) kinases (ROPK) are key virulence factors in T. gondii. To date, among the 28 ropk genes carried by E. tenella, only two to four were confirmed by proteomic analysis or immunostaining to be expressed at the sporozoite stage. We have previously shown that EtROP1 is implicated in the inhibition of host cell apoptosis by interacting with the cellular p53. This work functionally described the second ROP kinase expressed at the sporozoite stage in E. tenella. EtROP2 is an active kinase that phosphorylates cell substrates of approximately 50 kDa. Its overexpression leads to the shortening of the prepatent period and to the early development of first-generation schizonts. Conduction of RNA sequencing analysis and reverse transcriptase quantitative PCR (RT-qPCR) on the host cell allowed us to identify the mitogen-activated protein kinase (MAPK) pathway and the transcription factor cFos to be upregulated by EtROP2. We also showed by immunofluorescence assay that the active kinase EtROP2 is implicated in the p38 MAPK pathway activation. We established here that EtROP2 activates the p38 MAPK pathway through a direct or indirect phosphorylation, leading to the overexpression of the master transcription factor cFos known to be implicated in E. tenella development. IMPORTANCE Rhoptries are specialized secretory organelles found in zoite stages of apicomplexan parasites. In addition to well-conserved rhoptry neck proteins, their protein consists mostly of kinase proteins, highly divergent from eukaryotic kinases. Some of those kinases are described as major virulence factors in Toxoplasma gondii, secreted into the host cell to hijack signaling pathways. Most of those kinases remain to be characterized in Eimeria tenella. Deciphering their cellular function is a prerequisite to supporting their relevance as a druggable target in development of new means of Eimeria tenella control. Secreted divergent kinases that interact with host cell partners to modulate pathways are good candidates, as they coevolve with their host targets to ensure their function within the host and are less prone to mutations that would lead to drug resistance. The absence of any orthologous kinase in host cells makes these parasite kinases a promising drug target candidate.

Walking ability of individuals fitted with transfemoral bone-anchored prostheses: A comparative study of gait parameters.

OBJECTIVE: This study presents the walking abilities of participants fitted with transfemoral bone-anchored prostheses using a total of 14 gait parameters. DESIGN: Two-centre retrospective cross-sectional comparative study. SETTING: Research facilities equipped with tridimensional motion capture systems. PARTICIPANTS: Two control arms included eight able-bodied participants arm (54 ± 9 years, 1.75 ± 0.07 m, 76 ± 7 kg) and nine participants fitted with transfemoral socket-suspended prostheses arm (59 ± 9 years, 1.73 ± 0.07 m, 80 ± 16 kg). The intervention arm included nine participants fitted with transfemoral bone-anchored prostheses arm (51 ± 13 years, 1.78 ± 0.09 m, 87.3 ± 16.1 kg). INTERVENTION: Fitting of transfemoral bone-anchored prostheses. MAIN MEASURES: Comparisons were performed for two spatio-temporal, three spatial and nine temporal gait parameters. RESULTS: The cadence and speed of walking were 107 ± 6 steps/min and 1.23 ± 0.19 m/s for the able-bodied participants arm, 88 ± 7 steps/min and 0.87 ± 0.17 m/s for the socket-suspended prosthesis arm, and 96 ± 6 steps/min and 1.03 ± 0.17 m/s for bone-anchored prosthesis arm, respectively. Able-bodied participants and bone-anchored prosthesis arms were comparable in age, height, and body mass index as well as cadence and speed of walking, but the able-bodied participant arm showed a swing phase 31% shorter. Bone-anchored and socket-suspended prostheses arms were comparable for age, height, mass, and body mass index as well as cadence and speed of walking, but the bone-anchored prosthesis arm showed a step width and duration of double support in seconds 65% and 41% shorter, respectively. CONCLUSIONS: Bone-anchored and socket-suspended prostheses restored equally well the gait parameters at a self-selected speed. This benchmark data provides new insights into the walking ability of individuals using transfemoral bionics bone-anchored prostheses.

Anatomical registration of intracranial electrodes. Robust model-based localization and deformable smooth brain-shift compensation methods.

Precise electrode localization is important for maximizing the utility of intracranial EEG data. Electrodes are typically localized from post-implantation CT artifacts, but algorithms can fail due to low signal-to-noise ratio, unrelated artifacts, or high-density electrode arrays. Minimizing these errors usually requires time-consuming visual localization and can still result in inaccurate localizations. In addition, surgical implantation of grids and strips typically introduces non-linear brain deformations, which result in anatomical registration errors when post-implantation CT images are fused with the pre-implantation MRI images. Several projection methods are currently available, but they either fail to produce smooth solutions or do not account for brain deformations. To address these shortcomings, we propose two novel algorithms for the anatomical registration of intracranial electrodes that are almost fully automatic and provide highly accurate results. We first present GridFit, an algorithm that simultaneously localizes all contacts in grids, strips, or depth arrays by fitting flexible models to the electrodes' CT artifacts. We observed localization errors of less than one millimeter (below 8% relative to the inter-electrode distance) and robust performance under the presence of noise, unrelated artifacts, and high-density implants when we ran ~6000 simulated scenarios. Furthermore, we validated the method with real data from 20 intracranial patients. As a second registration step, we introduce CEPA, a brain-shift compensation algorithm that combines orthogonal-based projections, spring-mesh models, and spatial regularization constraints. When tested with real data from 15 patients, anatomical registration errors were smaller than those obtained for well-established alternatives. Additionally, CEPA accounted simultaneously for simple mechanical deformation principles, which is not possible with other available methods. Inter-electrode distances of projected coordinates smoothly changed across neighbor electrodes, while changes in inter-electrode distances linearly increased with projection distance. Moreover, in an additional validation procedure, we found that modeling resting-state high-frequency activity (75-145 Hz ) in five patients further supported our new algorithm. Together, GridFit and CEPA constitute a versatile set of tools for the registration of subdural grid, strip, and depth electrode coordinates that provide highly accurate results even in the most challenging implantation scenarios. The methods presented here are implemented in the iElectrodes open-source toolbox, making their use simple, accessible, and straightforward to integrate with other popular toolboxes used for analyzing electrophysiological data.

Influence of aging on the control of the whole-body angular momentum during volitional stepping: An UCM-based analysis.

Evidence suggests that whole-body angular momentum (WBAM) is a highly controlled mechanical variable for performing our daily motor activities safely and efficiently. Recent findings have revealed that, compared to young adults, older adults exhibit larger range of WBAM during various motor tasks, such as walking and stepping. However, it remains unclear whether these age-related changes are ascribed to a poorer control of WBAM with age or not. The purpose of the present study was to examine the effect of normal aging on WBAM control during stepping. Twelve young adults and 14 healthy older adults performed a series of volitional stepping at their preferred selected speed. An Uncontrolled Manifold (UCM) analysis was conducted to explore the presence of synergies among the angular momenta of the body segments (elemental variables) to control WBAM (performance variable); i.e., to stabilize or destabilize it. Results revealed the existence of a stronger synergy destabilizing the WBAM in the sagittal-plane older adults compared to young adults during stepping, while there was no difference between the two groups in the frontal and transversal planes. Although older participants also had a larger range of WBAM in the sagittal plane compared to young adults, we found no significant correlation between synergy index and the range of WBAM in the sagittal plane. We concluded that the age-related changes in WBAM during stepping are not ascribed to alterations in the ability to control this variable with aging.

Protection from successive Omicron variants with SARS-CoV-2 vaccine and monoclonal antibodies in kidney transplant recipients.

Introduction: Kidney transplant recipients (KTRs) are at high risk of severe COVID-19, even when they are fully vaccinated. Additional booster vaccinations or passive immunization with prophylactic monoclonal antibodies are recommended to increase their protection against severe COVID-19. Methods: Here, we describe the neutralization of SARS-CoV-2 Delta, Omicron BA.1, BA.2, BA.4, and BA.5 variants, firstly by 39 serum samples from vaccinated KTRs exhibiting anti-spike antibody concentrations ≥264 binding antibody units (BAU)/mL and, secondly, by tixagevimab/cilgavimab. Results: No neutralization was observed for 18% of the KTRs, while serum from only 46% of patients could neutralize the five variants. Cross-neutralization of the Delta and Omicron variants occurred for 65-87% of sera samples. The anti-spike antibody concentration correlated with neutralization activity for all the variants. The neutralization titers against the Delta variant were higher in vaccinated KTRs who had previously presented with COVID-19, compared to those KTRs who had only been vaccinated. Breakthrough infections occurred in 39% of the KTRs after the study. Tixagevimab/cilgavimab poorly neutralizes Omicron variants, particularly BA.5, and does not neutralize BQ.1, which is currently the most prevalent strain. Discussion: As a result, sera from seropositive vaccinated KTRs had poor neutralization of the successive Omicron variants. Several Omicron variants are able to escape tixagevimab/cilgavimab.

Successful weaning versus permanent cerebrospinal fluid diversion after aneurysmal subarachnoid hemorrhage: post hoc analysis of a Swiss multicenter study.

OBJECTIVE: Acute hydrocephalus is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH). Among patients needing CSF diversion, some cannot be weaned. Little is known about the comparative neurological, neuropsychological, and health-related quality-of-life (HRQOL) outcomes in patients with successful and unsuccessful CSF weaning. The authors aimed to assess outcomes of patients by comparing those with successful and unsuccessful CSF weaning; the latter was defined as occurring in patients with permanent CSF diversion at 3 months post-aSAH. METHODS: The authors included prospectively recruited alert (i.e., Glasgow Coma Scale score 13-15) patients with aSAH in this retrospective study from six Swiss neurovascular centers. Patients underwent serial neurological (National Institutes of Health Stroke Scale), neuropsychological (Montreal Cognitive Assessment), disability (modified Rankin Scale), and HRQOL (EuroQol-5D) examinations at < 72 hours, 14-28 days, and 3 months post-aSAH. RESULTS: Of 126 included patients, 54 (42.9%) developed acute hydrocephalus needing CSF diversion, of whom 37 (68.5%) could be successfully weaned and 17 (31.5%) required permanent CSF diversion. Patients with unsuccessful weaning were older (64.5 vs 50.8 years, p = 0.003) and had a higher rate of intraventricular hemorrhage (52.9% vs 24.3%, p = 0.04). Patients who succeed in restoration of physiological CSF dynamics improve on average by 2 points on the Montreal Cognitive Assessment between 48-72 hours and 14-28 days, whereas those in whom weaning fails worsen by 4 points (adjusted coefficient 6.80, 95% CI 1.57-12.04, p = 0.01). They show better neuropsychological recovery between 48-72 hours and 3 months, compared to patients in whom weaning fails (adjusted coefficient 7.60, 95% CI 3.09-12.11, p = 0.02). Patients who receive permanent CSF diversion (ventriculoperitoneal shunt) show significant neuropsychological improvement thereafter, catching up the delay in neuropsychological improvement between 14-28 days and 3 months post-aSAH. Neurological, disability, and HRQOL outcomes at 3 months were similar. CONCLUSIONS: These results show a temporary but clinically meaningful cognitive benefit in the first weeks after aSAH in successfully weaned patients. The resolution of this difference over time may be due to the positive effects of permanent CSF diversion and underlines its importance. Patients who do not show progressive neuropsychological improvement after weaning should be considered for repeat CT imaging to rule out chronic (untreated) hydrocephalus.