Search

Background and Objectives: The objective of this study was to assess the relationship between blood biomarkers of inflammation and lesion growth within the penumbra in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT)., Methods: The HIBISCUS-STROKE cohort enrolled patients admitted in the Lyon Stroke Center for an anterior circulation AIS treated with MT after brain MRI assessment. Lesion growth within the penumbra was assessed on day 6 MRI using a voxel-based nonlinear coregistration method and dichotomized into low and high according to the median value. C-reactive protein, interleukin (IL)-6, IL-8, IL-10, monocyte chemoattractant protein-1, soluble tumor necrosis factor receptor I, soluble form suppression of tumorigenicity 2 (sST2), soluble P-selectin, vascular cellular adhesion molecule-1, and matrix metalloproteinase-9 were measured in sera at 4 time points within the first 48 hours. Reperfusion was considered as successful if Thrombolysis in Cerebral Infarction score was 2b/2c/3. A multiple logistic regression model was performed to detect any association between area under the curve (AUC) of these biomarkers within the first 48 hours and a high lesion growth within the penumbra., Results: Ninety patients were included. The median lesion growth within the penumbra was 2.3 (0.7-6.2) mL. On multivariable analysis, a high sST2 AUC (OR 3.77, 95% CI 1.36-10.46), a high baseline DWI volume (OR 3.65, 95% CI 1.32-10.12), and a lack of successful reperfusion (OR 0.19, 95% CI 0.04-0.92) were associated with a high lesion growth within the penumbra. When restricting analyses to patients with successful reperfusion (n = 76), a high sST2 AUC (OR 5.03, 95% CI 1.64-15.40), a high baseline DWI volume (OR 3.74, 95% CI 1.22-11.53), and a high penumbra volume (OR 3.25, 95% CI 1.10-9.57) remained associated with a high lesion growth within the penumbra., Discussion: High sST2 levels within the first 48 hours are associated with a high lesion growth within the penumbra., (© 2022 American Academy of Neurology.)

Objectives: Cleft lip with/without cleft palate and cleft palate only is congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families. Orofacial clefts have a complex etiology resulting from genetic variants combined with environmental covariates. Recent genome-wide association studies and whole-exome sequencing for orofacial clefts identified significant genetic associations and variants in several genes. Of these, we investigated the role of common/rare variants in SHH, RORA, MRPL53, ACVR1, and GDF11., Materials and Methods: We sequenced these five genes in 1255 multi-ethnic cleft lip with/without palate and cleft palate only samples in order to find variants that may provide potential explanations for the missing heritability of orofacial clefts. Rare and novel variants were further analyzed using in silico predictive tools., Results: Ninteen total variants of interest were found, with variant types including stop-gain, missense, synonymous, intronic, and splice-site variants. Of these, 3 novel missense variants were found, one in SHH, one in RORA, and one in GDF11., Conclusion: This study provides evidence that variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts in various populations., (© 2021 Wiley Periodicals LLC.)

Since its discovery in Wuhan, China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread over the world, having a huge impact on people's lives and health. The respiratory system is often targeted in people with the coronavirus disease 2019 (COVID-19). The virus can also infect many organs and tissues in the body, including the reproductive system. The consequences of the SARS-CoV-2 infection on fertility and pregnancy in hosts are poorly documented. Available data on other coronaviruses, such as severe acute respiratory syndrome (SARS-CoV) and Middle Eastern Respiratory Syndrome (MERS-CoV) coronaviruses, identified pregnant women as a vulnerable group with increased pregnancy-related complications. COVID-19 was also shown to impact pregnancy, which can be seen in either the mother or the fetus. Pregnant women more likely require COVID-19 intensive care treatment than non-pregnant women, and they are susceptible to giving birth prematurely and having their newborns admitted to the neonatal intensive care unit. Angiotensin converting enzyme 2 (ACE2), a key player of the ubiquitous renin-angiotensin system (RAS), is the principal host cellular receptor for SARS-CoV-2 spike protein. ACE2 is involved in the regulation of both male and female reproductive systems, suggesting that SARS-CoV-2 infection and associated RAS dysfunction could affect reproduction. Herein, we review the current knowledge about COVID-19 consequences on male and female fertility, pregnant women, and their fetuses. Furthermore, we describe the effects of COVID-19 vaccination on reproduction.

Gait, balance, and coordination are important in the development of chronic disease, but the ability to accurately assess these in the daily lives of patients may be limited by traditional biased assessment tools. Wearable sensors offer the possibility of minimizing the main limitations of traditional assessment tools by generating quantitative data on a regular basis, which can greatly improve the home monitoring of patients. However, these commercial sensors must be validated in this context with rigorous validation methods. This scoping review summarizes the state-of-the-art between 2010 and 2020 in terms of the use of commercial wearable devices for gait monitoring in patients. For this specific period, 10 databases were searched and 564 records were retrieved from the associated search. This scoping review included 70 studies investigating one or more wearable sensors used to automatically track patient gait in the field. The majority of studies (95%) utilized accelerometers either by itself (N = 17 of 70) or embedded into a device (N = 57 of 70) and/or gyroscopes (51%) to automatically monitor gait via wearable sensors. All of the studies (N = 70) used one or more validation methods in which "ground truth" data were reported. Regarding the validation of wearable sensors, studies using machine learning have become more numerous since 2010, at 17% of included studies. This scoping review highlights the current state of the ability of commercial sensors to enhance traditional methods of gait assessment by passively monitoring gait in daily life, over long periods of time, and with minimal user interaction. Considering our review of the last 10 years in this field, machine learning approaches are algorithms to be considered for the future. These are in fact data-based approaches which, as long as the data collected are numerous, annotated, and representative, allow for the training of an effective model. In this context, commercial wearable sensors allowing for increased data collection and good patient adherence through efforts of miniaturization, energy consumption, and comfort will contribute to its future success.

Background: Predictive maps of the final infarct may help therapeutic decisions in acute ischemic stroke patients. Our objectives were to assess whether integrating the reperfusion status into deep learning models would improve their performance, and to compare them to current clinical prediction methods., Methods: We trained and tested convolutional neural networks (CNNs) to predict the final infarct in acute ischemic stroke patients treated by thrombectomy in our center. When training the CNNs, non-reperfused patients from a non-thrombectomized cohort were added to the training set to increase the size of this group. Baseline diffusion and perfusion-weighted magnetic resonance imaging (MRI) were used as inputs, and the lesion segmented on day-6 MRI served as the ground truth for the final infarct. The cohort was dichotomized into two subsets, reperfused and non-reperfused patients, from which reperfusion status specific CNNs were developed and compared to one another, and to the clinically-used perfusion-diffusion mismatch model. Evaluation metrics included the Dice similarity coefficient (DSC), precision, recall, volumetric similarity, Hausdorff distance and area-under-the-curve (AUC)., Results: We analyzed 109 patients, including 35 without reperfusion. The highest DSC were achieved in both reperfused and non-reperfused patients (DSC = 0.44 ± 0.25 and 0.47 ± 0.17, respectively) when using the corresponding reperfusion status-specific CNN. CNN-based models achieved higher DSC and AUC values compared to those of perfusion-diffusion mismatch models (reperfused patients: AUC = 0.87 ± 0.13 vs 0.79 ± 0.17, P < 0.001; non-reperfused patients: AUC = 0.81 ± 0.13 vs 0.73 ± 0.14, P < 0.01, in CNN vs perfusion-diffusion mismatch models, respectively)., Conclusion: The performance of deep learning models improved when the reperfusion status was incorporated in their training. CNN-based models outperformed the clinically-used perfusion-diffusion mismatch model. Comparing the predicted infarct in case of successful vs failed reperfusion may help in estimating the treatment effect and guiding therapeutic decisions in selected patients., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The development of the face occurs during the early days of intrauterine life by the formation of facial processes from the first Pharyngeal arch. Derangement in these well-organized fusion events results in Orofacial clefts (OFC). Van der Woude syndrome (VWS) is one of the most common causes of syndromic cleft lip and/or palate accounting for 2% of all cases. Mutations in the IRF6 gene account for 70% of cases with the majority of these mutations located in the DNA-binding (exon 3, 4) or protein-binding domains (exon 7-9). The current study was designed to update the list of IRF6 variants reported for VWS by compiling all the published mutations from 2013 to date as well as including the previously unreported VWS cases from Africa and Puerto Rico., Methods: We used PubMed with the search terms; "Van der Woude syndrome," "Popliteal pterygium syndrome," "IRF6," and "Orofacial cleft" to identify eligible studies. We compiled the CADD score for all the mutations to determine the percentage of deleterious variants., Results: Twenty-one new mutations were identified from nine papers. The majority of these mutations were in exon 4. Mutations in exon 3 and 4 had CADD scores between 20 and 30 and mutations in exon 7-9 had CADD scores between 30 and 40. The presence of higher CADD scores in the protein-binding domain (exon 7-9) further confirms the crucial role played by this domain in the function of IRF6. In the new cases, we identified five IRF6 mutations, three novel missense mutations (p.Phe36Tyr, p.Lys109Thr, and p.Gln438Leu), and two previously reported nonsense mutations (p.Ser424*and p.Arg250*)., Conclusion: Mutations in the protein and DNA-binding domains of IRF6 ranked among the top 0.1% and 1% most deleterious genetic mutations, respectively. Overall, these findings expand the range of VWS mutations and are important for diagnostic and counseling purposes., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

The problem of final tissue outcome prediction of acute ischemic stroke is assessed from physically realistic simulated perfusion magnetic resonance images. Different types of simulations with a focus on the arterial input function are discussed. These simulated perfusion magnetic resonance images are fed to convolutional neural network to predict real patients. Performances close to the state-of-the-art performances are obtained with a patient specific approach. This approach consists in training a model only from simulated images tuned to the arterial input function of a tested real patient. This demonstrates the added value of physically realistic simulated images to predict the final infarct from perfusion., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

We address the medical image analysis issue of predicting the final lesion in stroke from early perfusion magnetic resonance imaging. The classical processing approach for the dynamical perfusion images consists in a temporal deconvolution to improve the temporal signals associated with each voxel before performing prediction. We demonstrate here the value of exploiting directly the raw perfusion data by encoding the local environment of each voxel as a spatio-temporal texture, with an observation scale larger than the voxel. As a first illustration for this approach, the textures are characterized with local binary patterns and the classification is performed using a standard support vector machine (SVM). This simple machine learning classification scheme demonstrates results with 95% accuracy on average while working only raw perfusion data. We discuss the influence of the observation scale and evaluate the interest of using post-processed perfusion data with this approach., (Copyright © 2018. Published by Elsevier B.V.)

The use of cultured human keratinocytes in an in vitro comparison of topical antibacterial toxicity for epithelial cells was examined. The complement of three assessments allows testing of epithelial migration, growth, and survival. The three assessments included (1) flow cytometry for determination of cell survival, (2) a comparison of confluent cell culture growth after antibacterial exposures, and (3) an evaluation of cell migration using a technique of dermal explants to study radial migration. A comparative ranking of the toxicities of the various topical antibacterials was determined with the three assessments. This has confirmed anecdotal reports that many of the topical antibacterials are cell-toxic and may inhibit wound healing. This information can be directly extrapolated to the clinical setting, unlike many of the animal data for wound healing that currently exist.

Temporary restoration of capillary skin blood flow can be established by using leeches or by the creation of a dermal wound and the promotion of continued bleeding from the wound site in a flap with venous occlusion. An increasing restoration of capillary flow occurred with initial application of the leech and tended to exceed other techniques of restoring flow. However, all techniques of exsanguination, including leech therapy, restored very low perfusion over a two-hour course of therapy for a volume of tissue simulating a distal finger replant. The temporary increase in flap perfusion with a single leech application was greatest during the feeding activity of the leech and tapered off after the leech was satiated, to approximate flows achieved with local heparin injection and a punch wound.

A prolonged preoperative ischemic interval decreases the chances for successful replantation of an amputated limb. Skeletal muscle is especially sensitive to periods of prolonged ischemia. It is now hypothesized that significant tissue injury occurs during reperfusion, when oxygen-rich blood contacts anaerobic metabolites forming toxic oxygen free radicals. A replantation model, using the rabbit hind limb tibialis anterior muscle, was developed to assess muscle function and histological appearance following ischemic intervals of five and eight hours. Muscle strength five weeks after injury was used as a functional measurement of tissue damage. The effects of the superoxide free radical scavenger superoxide dismutase (SOD) and the hydroxyl radical scavenger dimethylsulfoxide (DMSO), administered systemically just before reperfusion, were studied. Muscle treated with SOD following five hours of ischemia had essentially normal strength and histological appearance; however, there was no protective effect after eight hours. DMSO treatment had no beneficial effects after five hours of ischemia, but after eight hours DMSO-treated muscle had significantly better function than untreated muscle. Histological examination confirmed the functional results. Clinical treatment of ischemic limbs with free radical scavengers before revascularization may aid in avoiding reperfusion injury and may improve survival and later muscle function.

Using the rat sciatic nerve model, we evaluated the merits of homologous fibrin glue in the repair of peripheral nerve transections as compared to standard epineural suture repairs. A total of four study groups were used, with 10 animals assigned to each group. In group I, the transected sciatic nerve was repaired with six interrupted 10-0 nylon sutures; in group II, only two interrupted sutures were used; in group III, a two-suture repair was reinforced with fibrin glue; and in group IV, only fibrin glue was used. All animals were sacrificed at 8 weeks, and histologic sections evaluated. When fibrin alone was used, dehiscence occurred in 80 percent of the animals, and as reinforcement of a two-suture repair, it only increased the inflammatory reaction.

A case of cardiac fibroma in a 58-year-old woman with a history of atrioventricular block is described. The patient died suddenly at home 6 days following the insertion of a pacemaker. Review of the pertinent literature is presented.