Patient with a heterozygous pathogenic variant in CSNK2A1 gene: A new case to update the Okur-Chung neurodevelopmental syndrome.

The autosomal dominant Okur-Chung neurodevelopmental syndrome (OCNDS: OMIM #617062) is a rare neurodevelopmental disorder first described in 2016. Features include developmental delay (DD), intellectual disability (ID), behavioral problems, hypotonia, language deficits, congenital heart abnormalities, and non-specific dysmorphic facial features. OCNDS is caused by heterozygous pathogenic variants in CSNK2A1 (OMIM *115440; NM_177559.3). To date, 160 patients have been diagnosed worldwide. The number will likely increase due to the growing use of exome sequencing (ES) and genome sequencing (GS). Here, we describe a novel OCNDS patient carrying a CSNK2A1 variant (NM_177559.3:c.140G>A; NP_808227.1:p.Arg47Gln). Phenotypically, he presented with DD, ID, generalized hypotonia, speech delay, short stature, microcephaly, and dysmorphic features such as low-set ears, hypertelorism, thin upper lip, and a round face. The patient showed several signs not yet described that may extend the phenotypic spectrum of OCNDS. These include prenatal bilateral clubfeet, exotropia, and peg lateral incisors. However, unlike the majority of descriptions, he did not present sleep disturbance, seizures or gait difficulties. A literature review shows phenotypic heterogeneity for OCNDS, whether these patients have the same variant or not. This case report is an opportunity to refine the phenotype of this syndrome and raise the question of the genotype-phenotype correlation.

Walk-through flat panel total-body PET: a patient-centered design for high throughput imaging at lower cost using DOI-capable high-resolution monolithic detectors.

PURPOSE: Long axial field-of-view (LAFOV) systems have a much higher sensitivity than standard axial field-of-view (SAFOV) PET systems for imaging the torso or full body, which allows faster and/or lower dose imaging. Despite its very high sensitivity, current total-body PET (TB-PET) throughput is limited by patient handling (positioning on the bed) and often a shortage of available personnel. This factor, combined with high system costs, makes it hard to justify the implementation of these systems for many academic and nearly all routine nuclear medicine departments. We, therefore, propose a novel, cost-effective, dual flat panel TB-PET system for patients in upright standing positions to avoid the time-consuming positioning on a PET-CT table; the walk-through (WT) TB-PET. We describe a patient-centered, flat panel PET design that offers very efficient patient throughput and uses monolithic detectors (with BGO or LYSO) with depth-of-interaction (DOI) capabilities and high intrinsic spatial resolution. We compare system sensitivity, component costs, and patient throughput of the proposed WT-TB-PET to a SAFOV (= 26 cm) and a LAFOV (= 106 cm) LSO PET systems. METHODS: Patient width, height (= top head to start of thighs) and depth (= distance from the bed to front of patient) were derived from 40 randomly selected PET-CT scans to define the design dimensions of the WT-TB-PET. We compare this new PET system to the commercially available Siemens Biograph Vision 600 (SAFOV) and Siemens Quadra (LAFOV) PET-CT in terms of component costs, system sensitivity, and patient throughput. System cost comparison was based on estimating the cost of the two main components in the PET system (Silicon Photomultipliers (SiPMs) and scintillators). Sensitivity values were determined using Gate Monte Carlo simulations. Patient throughput times (including CT and scout scan, patient positioning on bed and transfer) were recorded for 1 day on a Siemens Vision 600 PET. These timing values were then used to estimate the expected patient throughput (assuming an equal patient radiotracer injected activity to patients and considering differences in system sensitivity and time-of-flight information) for WT-TB-PET, SAFOV and LAFOV PET. RESULTS: The WT-TB-PET is composed of two flat panels; each is 70 cm wide and 106 cm high, with a 50-cm gap between both panels. These design dimensions were justified by the patient sizes measured from the 40 random PET-CT scans. Each panel consists of 14 × 20 monolithic BGO detector blocks that are 50 × 50 × 16 mm in size and are coupled to a readout with 6 × 6 mm SiPMs arrays. For the WT-TB-PET, the detector surface is reduced by a factor of 1.9 and the scintillator volume by a factor of 2.2 compared to LAFOV PET systems, while demonstrating comparable sensitivity and much better uniform spatial resolution (< 2 mm in all directions over the FOV). The estimated component cost for the WT-TB-PET is 3.3 × lower than that of a 106 cm LAFOV system and only 20% higher than the PET component costs of a SAFOV. The estimated maximum number of patients scanned on a standard 8-h working day increases from 28 (for SAFOV) to 53-60 (for LAFOV in limited/full acceptance) to 87 (for the WT-TB-PET). By scanning faster (more patients), the amount of ordered activity per patient can be reduced drastically: the WT-TB-PET requires 66% less ordered activity per patient than a SAFOV. CONCLUSIONS: We propose a monolithic BGO or LYSO-based WT-TB-PET system with DOI measurements that departs from the classical patient positioning on a table and allows patients to stand upright between two flat panels. The WT-TB-PET system provides a solution to achieve a much lower cost TB-PET approaching the cost of a SAFOV system. High patient throughput is increased by fast patient positioning between two vertical flat panel detectors of high sensitivity. High spatial resolution (< 2 mm) uniform over the FOV is obtained by using DOI-capable monolithic scintillators.

[Refractory pneumonia : when evoke an Adult-Onset Still's Disease ? Case report and review of literature]. / Pneumonie réfractaire : quand évoquer la maladie de Still de l'adulte ? - Rapport de cas et revue de la littérature.

Adult-Onset Still's Disease (AOSD) is an inflammatory systemic disease, including fever, arthralgia and rash. The disease can also cause organic involvement, and lead to serious complications. We report the case of a patient who presented a pulmonary form of AOSD, initially diagnosed and treated as pneumonia. Marked hyperferritinemia oriented us to the right diagnosis. In this article, we proceed to a review of literature to look for a better comprehension of physiopathology of pulmonary involvement in AOSD, and to withhold some practical advice in the diagnostic procedure.

La maladie de Still de l'adulte (MSA) est une maladie systémique inflammatoire, comprenant classiquement fièvre, arthralgies et rash cutané. La maladie peut également entraîner des atteintes d'organes et de graves complications. Nous rapportons le cas d'un patient qui a présenté une MSA avec atteinte pulmonaire, diagnostiquée et traitée initialement comme pneumonie. Une hyperferritinémie marquée nous a orientés vers le bon diagnostic. Dans cet article, nous réalisons une revue de la littérature visant à mieux comprendre la physiopathologie de l'atteinte pulmonaire de la MSA et d'en retenir des conseils pratiques dans l'aide au diagnostic.

Image Denoising of Low-Dose PET Mouse Scans with Deep Learning: Validation Study for Preclinical Imaging Applicability.

PURPOSE: Positron emission tomography (PET) image quality can be improved by higher injected activity and/or longer acquisition time, but both may often not be practical in preclinical imaging. Common preclinical radioactive doses (10 MBq) have been shown to cause deterministic changes in biological pathways. Reducing the injected tracer activity and/or shortening the scan time inevitably results in low-count acquisitions which poses a challenge because of the inherent noise introduction. We present an image-based deep learning (DL) framework for denoising lower count micro-PET images. PROCEDURES: For 36 mice, a 15-min [18F]FDG (8.15 ± 1.34 MBq) PET scan was acquired at 40 min post-injection on the Molecubes ß-CUBE (in list mode). The 15-min acquisition (high-count) was parsed into smaller time fractions of 7.50, 3.75, 1.50, and 0.75 min to emulate images reconstructed at 50, 25, 10, and 5% of the full counts, respectively. A 2D U-Net was trained with mean-squared-error loss on 28 high-low count image pairs. RESULTS: The DL algorithms were visually and quantitatively compared to spatial and edge-preserving denoising filters; the DL-based methods effectively removed image noise and recovered image details much better while keeping quantitative (SUV) accuracy. The largest improvement in image quality was seen in the images reconstructed with 10 and 5% of the counts (equivalent to sub-1 MBq or sub-1 min mouse imaging). The DL-based denoising framework was also successfully applied on the NEMA-NU4 phantom and different tracer studies ([18F]PSMA, [18F]FAPI, and [68 Ga]FAPI). CONCLUSION: Visual and quantitative results support the superior performance and robustness in image denoising of the implemented DL models for low statistics micro-PET. This offers much more flexibility in optimizing preclinical, longitudinal imaging protocols with reduced tracer doses or shorter durations.

Dose reduction and image enhancement in micro-CT using deep learning.

BACKGROUND: In preclinical settings, micro-computed tomography (CT) provides a powerful tool to acquire high resolution anatomical images of rodents and offers the advantage to in vivo non-invasively assess disease progression and therapy efficacy. Much higher resolutions are needed to achieve scale-equivalent discriminatory capabilities in rodents as those in humans. High resolution imaging however comes at the expense of increased scan times and higher doses. Specifically, with preclinical longitudinal imaging, there are concerns that dose accumulation may affect experimental outcomes of animal models. PURPOSE: Dose reduction efforts under the ALARA (as low as reasonably achievable) principles are thus a key point of attention. However, low dose CT acquisitions inherently induce higher noise levels which deteriorate image quality and negatively impact diagnostic performance. Many denoising techniques already exist, and deep learning (DL) has become increasingly popular for image denoising, but research has mostly focused on clinical CT with limited studies conducted on preclinical CT imaging. We investigate the potential of convolutional neural networks (CNN) for restoring high quality micro-CT images from low dose (noisy) images. The novelty of the CNN denoising frameworks presented in this work consists of utilizing image pairs with realistic CT noise present in the input as well as the target image used for the model training; a noisier image acquired with a low dose protocol is matched to a less noisy image acquired with a higher dose scan of the same mouse. METHODS: Low and high dose ex vivo micro-CT scans of 38 mice were acquired. Two CNN models, based on a 2D and 3D four-layer U-Net, were trained with mean absolute error (30 training, 4 validation and 4 test sets). To assess denoising performance, ex vivo mice and phantom data were used. Both CNN approaches were compared to existing methods, like spatial filtering (Gaussian, Median, Wiener) and iterative total variation image reconstruction algorithm. Image quality metrics were derived from the phantom images. A first observer study (n = 23) was set-up to rank overall quality of differently denoised images. A second observer study (n = 18) estimated the dose reduction factor of the investigated 2D CNN method. RESULTS: Visual and quantitative results show that both CNN algorithms exhibit superior performance in terms of noise suppression, structural preservation and contrast enhancement over comparator methods. The quality scoring by 23 medical imaging experts also indicates that the investigated 2D CNN approach is consistently evaluated as the best performing denoising method. Results from the second observer study and quantitative measurements suggest that CNN-based denoising could offer a 2-4× dose reduction, with an estimated dose reduction factor of about 3.2 for the considered 2D network. CONCLUSIONS: Our results demonstrate the potential of DL in micro-CT for higher quality imaging at low dose acquisition settings. In the context of preclinical research, this offers promising future prospects for managing the cumulative severity effects of radiation in longitudinal studies.

Toughening colloidal gels using rough building blocks.

Colloidal gels, commonly used as mesoporous intermediates or functional materials, suffer from brittleness, often showing small yield strains on the order of 1% or less for gelled colloidal suspensions. The short-range adhesive forces in most such gels are central forces-combined with the smooth morphology of particles, the resistance to yielding and shear-induced restructuring is limited. In this study, we propose an innovative approach to improve colloidal gels by introducing surface roughness to the particles to change the yield strain, giving rise to non-central interactions. To elucidate the effects of particle roughness on gel properties, we prepared thermoreversible gels made from rough or smooth silica particles using a reliable click-like-chemistry-based surface grafting technique. Rheological and optical characterization revealed that rough particle gels exhibit enhanced toughness and self-healing properties. These remarkable properties can be utilized in various applications, such as xerogel fabrication and high-fidelity extrusion 3D-printing, as we demonstrate in this study.

Anisotropic wood-hydrogel composites: Extending mechanical properties of wood towards soft materials' applications.

Delignified wood (DW) offers a versatile platform for the manufacturing of composites, with material properties ranging from stiff to soft and flexible by preserving the preferential fiber directionality of natural wood through a structure-retaining production process. This study presents a facile method for fabricating anisotropic and mechanically tunable DW-hydrogel composites. These composites were produced by infiltrating delignified spruce wood with an aqueous gelatin solution followed by chemical crosslinking. The mechanical properties could be modulated across a broad strength and stiffness range (1.2-18.3 MPa and 170-1455 MPa, respectively) by varying the crosslinking time. The diffusion-led crosslinking further allowed to manufacture mechanically graded structures. The resulting uniaxial, tubular structure of the anisotropic DW-hydrogel composite enabled the alignment of murine fibroblasts in vitro, which could be utilized in future studies on potential applications in tissue engineering.

Performance evaluation of a micro-CT system for laboratory animal imaging with iterative reconstruction capabilities.

BACKGROUND: In recent years, there has been a rapid proliferation in micro-computed tomography (micro-CT) systems becoming more available for routine preclinical research, with applications in many areas, including bone, lung, cancer, and cardiac imaging. Micro-CT provides the means to non-invasively acquire detailed anatomical information, but high-resolution imaging comes at the cost of longer scan times and higher doses, which is not desirable given the potential risks related to x-ray radiation. To achieve dose reduction and higher throughputs without compromising image quality, fewer projections can be acquired. This is where iterative reconstruction methods can have the potential to reduce noise since these algorithms can better handle sparse projection data, compared to filtered backprojection PURPOSE: We evaluate the performance characteristics of a compact benchtop micro-CT scanner that provides iterative reconstruction capabilities with GPU-based acceleration. We thereby investigate the potential benefit of iterative reconstruction for dose reduction. METHODS: Based on a series of phantom experiments, the benchtop micro-CT system was characterized in terms of image uniformity, noise, low contrast detectability, linearity, and spatial resolution. Whole-body images of a plasticized ex vivo mouse phantom were also acquired. Different acquisition protocols (general-purpose versus high-resolution, including low dose scans) and different reconstruction strategies (analytic versus iterative algorithms: FDK, ISRA, ISRA-TV) were compared. RESULTS: Signal uniformity was maintained across the radial and axial field-of-view (no cupping effect) with an average difference in Hounsfield units (HU) between peripheral and central regions below 50. For low contrast detectability, regions with at least ∆HU of 40 to surrounding material could be discriminated (for rods of 2.5 mm diameter). A high linear correlation (R2  = 0.997) was found between measured CT values and iodine concentrations (0-40 mg/ml). Modulation transfer function (MTF) calculations on a wire phantom evaluated a resolution of 10.2 lp/mm at 10% MTF that was consistent with the 8.3% MTF measured on the 50 µm bars (10 lp/mm) of a bar-pattern phantom. Noteworthy changes in signal-to-noise and contrast-to-noise values were found for different acquisition and reconstruction protocols. Our results further showed the potential of iterative reconstruction to deliver images with less noise and artefacts. CONCLUSIONS: In summary, the micro-CT system that was evaluated in the present work was shown to provide a good combination of performance characteristics between image uniformity, low contrast detectability, and resolution in short scan times. With the iterative reconstruction capabilities of this micro-CT system in mind (ISRA and ISRA-TV), the adoption of such algorithms by GPU-based acceleration enables the integration of noise reduction methods which here demonstrated potential for high-quality imaging at reduced doses.

Prognostic factors for intramedullary nailing in radial neck fracture in children.

INTRODUCTION: Radial fracture accounts for 1% of fractures in children. It is potentially serious, and treatment is controversial. Several studies assessed prognostic factors, only one of which used exclusive intramedullary nailing, despite this being the gold standard. HYPOTHESIS: Open surgery provides poor functional results in radial neck fracture. MATERIAL AND METHOD: All patients undergoing reduction and internal fixation of radial neck fracture between 2005 and 2015 were analysed. Inclusion criteria comprised Jeffery type 1 fracture with open growth plate, complete file, and ≥1 year's follow-up. Treatment systematically comprised Métaizeau intramedullary nailing, with crossover to open reduction only in case of failure. Good results were defined as full range of motion and pain-free elbow. RESULTS: Fifty-six patients were included: 33 girls, 23 boys; mean age, 9 years. On the Judet classification modified by Métaizeau, 4 fractures were grade 2, 29 grade 3, 15 grade 4A and 8 grade 4B. Closed reduction was performed in 48 cases, including 8 with the help of percutaneous leverage effect. Eight required a surgical approach. Twenty-three showed postoperative reduction defect. At a mean 74 months' follow-up, at a mean age of 15 years, 37 patients had reached full skeletal maturity. Sixteen had poor results. Open reduction was associated with poor outcome (p<0.01). Age, initial epiphyseal tilt, associated lesions, immobilisation time, time to nail removal and residual tilt after reduction did not significantly affect outcome (p-values>0.05). Percutaneous leverage effect had no impact on the quality of results (p=1). DISCUSSION: Open reduction is to be avoided in radial neck fracture. A prospective study is needed to assess remodelling potential according to age. LEVEL OF EVIDENCE: IV, retrospective study.

Outlooks on Three-Dimensional Printing for Ocular Biomaterials Research.

Given its potential for high-resolution, customizable, and waste-free fabrication of medical devices and in vitro biological models, 3-dimensional (3D) bioprinting has broad utility within the biomaterials field. Indeed, 3D bioprinting has to date been successfully used for the development of drug delivery systems, the recapitulation of hard biological tissues, and the fabrication of cellularized organ and tissue-mimics, among other applications. In this study, we highlight convergent efforts within engineering, cell biology, soft matter, and chemistry in an overview of the 3D bioprinting field, and we then conclude our work with outlooks toward the application of 3D bioprinting for ocular research in vitro and in vivo.

Bone maturation of MRI residual developmental dysplasia of the hip with discrepancy between osseous and cartilaginous acetabular index.

Quality of spontaneous amelioration of residual developmental dysplasia of the hip (DDH) is nowadays not possible to predict. Normal age-related values of the osseous acetabular index (OAI), cartilaginous acetabular index and labral acetabular index have been established on MRI. In this study, MRI of dysplastic hips has been evaluated, and further osseous acetabular maturation was followed-up over time on pelvic radiography to find a correlation between MRI findings and radiological evolution. This is a retrospective single-centre study. Children with DDH who had a pelvic MRI between February 2007 and June 2014 were included. AI was measured for osseous (OAI), cartilaginous (cartilaginous acetabular index) and labral (labral acetabular index) values on MRI. OAI was thereafter recorded on each available radiograph during follow-up. A total of 20 hips were included. The mean age at MRI diagnosis was 3.55 years. Two types of DDH were observed: harmonious dysplasia, associated with an osseous and cartilaginous defect (group A, n = 14), and divergent dysplasia, associated with an osseous defect but with sufficient cartilaginous coverage (group B, n = 6). The mean age at final radiological follow-up was 7.6 and 8.3 years (P = 0.7408), respectively. In group A, four (28.6%) children older than 6 years had an OAI of less than 18°, whereas only two (33.3%) children older than 6 years had an OAI less than 18° in group B (P = 0.0117). This study shows that, in one-third of cases, divergent dysplasia leads to a spontaneous recovery. MRI should be used early to accurately diagnose and follow-up DDH cases and allow surgeons to justify the required surgical treatment. Level of Evidence: IV.

[Equity and planning: a critical analysis of a third generation regional healthcare management program]. / Equité et planification: analyse critique d'un schéma régional d'organisation sanitaire de troisième génération "perinatalité".

The third generation of the regional healthcare organization plan (Sros III) proposes to develop the organisation of healthcare and its management according to evolution of its activities and the populations concerned. At the time of a strategic analysis of SROS III (what we refer to as its perinatal period), the question is whether promoters can move from an approach based on accessibility (egalitarian equity) to a needs-based approach (differential equity), which although more complicated in to apply and implement, was found be much better adapted to healthcare users. The research is derived from an analysis of documents from November 2004 to November 2006. A university public hospital developed the data which supported a proposal to shift from level I to level II. This proposition was retained in the territory's medical plan authorized by the regional health authorities. Health professionals and the architects of the healthcare plan have the capacity to new organizations responsible for taking into account the activities and healthcare needs of the population in order to initiate and establish differential equity.

Rehospitalization following a stay in geriatric rehabilitation wards: rates and predictive factors.

Hospitalization in the elderly patients is highly associated with morbi-mortality. Geriatric post-acute and rehabilitation care wards are designed to provide care and to implement life project of elderly patients. Objective of this study was to characterize rehospitalizations after a stay in geriatric post-acute and rehabilitation care wards. METHODS: The study was retrospective, case-control, including all the patients hospitalized in the 4 geriatric post-acute and rehabilitation care wards of a hospital in Paris (France) and returned at home. Data collection was carried out on the basis of the hospitalization report and the information system of the hospital. Rehospitalizations were documented by the information system as well as by telephone interview. We compared patients according to whether they had been rehospitalized or not within 60 days after discharge. RESULTS: Out of a total of 1,063 stays during a 12 months period, 435 (41%) were discharged at home. Re-admission rate was 10.1% at 30 days and 18.4% at 90 days. Mean age of rehospitaliszed patients was 87.2 years ± 5.3 vs 87.9 years ± 5.8 for non-rehospitalized patients. Patients rehospitalized had more often a delirium during the prior hospitalization. CONCLUSION: Unplanned rehospitalisation is a major public health issue and should be prevented particularly after a stay in a geriatric post-acute and rehabilitation care wards.

[Representation and practice about "chimical restraints": qualitative study with 50 health worker]. / Interprétation et pratiques autour du terme "contention chimique" : étude qualitative auprès de 50 professionnels de santé.

The term "chemical restraints" seems to be used in medical practice, but does not have the same meaning for all French health care professionals. In available literature it is considered as use of psychotropic medications for behavioral disorders. We used qualitative research method based on semi-directive interviews, in order to better understand meaning of "chemical restraint" term for geriatric medical and paramedical personnel. This term is well understood, rarely used, wrong for some professional because "drugs do not hold". The term of "physical restraint" has a more tangible reality. The term of "sedation of psychocomportemental troubles" is more common and seems to have a less pejorative connotation. In practice chemical restraint may correspond to emergency use of benzodiazepines or neuroleptics by injection at doses leading to the patient's sedation without his consent.

[Impact of low-molecular-weight heparin practice guidelines in a geriatric hospital]. / Impact d'un guide de bon usage des anticoagulants sur la prescription des héparines de bas poids moléculaire dans un hôpital gériatrique.

The purpose of this study was to assess the impact of good use of anticoagulants guidelines implementation on low molecular weight heparin (LMWH) prescription in a french geriatric hospital. This interventional "before and after" study was conduced by the same geriatrician on a d-day in 2006 and 2009. Guidelines for anticoagulant's prescription based on selected references in the literature was established by an expert's consensus and implemented in 2008. Data were collected in all departments at the Sainte-Perine geriatric hospital for each patient with an LMWH prescription. Assessment was based on quality judgment criteria (indication, dosage, treatment duration, biological monitoring of LMWH). Data were collected for 72 prescriptions prior to the guidelines implementation and for 54 after. Sex-ratio, mean age and percentage of LMWH prescription did not differ significantly between the two periods. There was a better conformity for LMWH dosage prescription (p = 0.002) and biological monitoring prescription (p = 0.036) after the guidelines implementation. Conformity of LMWH indication and treatment duration were improved but the difference remained not significant (respectively p = 0.49 and p = 0.80). Implementing guidelines for LMWH use in geriatrics can improve quality of prescription. The impact was effective but limited. These guidelines are now in general use in the Sainte-Perine hospital.

Buttock claudication disclosing a thrombosis of the superior left gluteal artery: Report of a case diagnosed by a selective arteriography of the iliac artery, and cured by per-cutaneous stenting.

We report on a case of left buttock claudication, occurring consistently after 150 meters walking, and disappearing after a short rest. As magnetic resonance angiography (MRA) did not show any explanation for this claudication, a selective angiography of left internal iliac artery was requested, which clearly identified a tight stenosis of the onset of the left superior gluteal artery. A per-cutaneous angioplasty together with stenting of this artery, induced a prompt and complete relief of pain at the three months follow-up visit.