Active bone marrow segmentation based on computed tomography imaging in anal cancer patients: A machine-learning-based proof of concept.

PURPOSE: Different methods are available to identify haematopoietically active bone marrow (ActBM). However, their use can be challenging for radiotherapy routine treatments, since they require specific equipment and dedicated time. A machine learning (ML) approach, based on radiomic features as inputs to three different classifiers, was applied to computed tomography (CT) images to identify haematopoietically active bone marrow in anal cancer patients. METHODS: A total of 40 patients was assigned to the construction set (training set + test set). Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography (18FDG-PET) images were used to detect the active part of the pelvic bone marrow (ActPBM) and stored as ground-truth for three subregions: iliac, lower pelvis and lumbosacral bone marrow (ActIBM, ActLPBM, ActLSBM). Three parameters were used for the correspondence analyses between 18FDG-PET and ML classifiers: DICE index, Precision and Recall. RESULTS: For the 40-patient cohort, median values [min; max] of the Dice index were 0.69 [0.20; 0.84], 0.76 [0.25; 0.89], and 0.36 [0.15; 0.67] for ActIBM, ActLSBM, and ActLPBM, respectively. The Precision/Recall (P/R) ratio median value for the ActLPBM structure was 0.59 [0.20; 1.84] (over segmentation), while for the other two subregions the P/R ratio median has values of 1.249 [0.43; 4.15] for ActIBM and 1.093 [0.24; 1.91] for ActLSBM (under segmentation). CONCLUSION: A satisfactory degree of overlap compared to 18FDG-PET was found for 2 out of the 3 subregions within pelvic bones. Further optimization and generalization of the process is required before clinical implementation.

First-Pass Effect in M1-Occlusion Stroke Patients Treated with Combined Stent-Retriever/Large-Bore Distal Aspiration Catheter Thrombectomy.

INTRODUCTION: Combined stent-retriever/large-bore distal aspiration catheter (LB-DAC) thrombectomy was recently introduced to treat large-vessel occlusion; however, it is unclear whether larger inner diameters improve outcomes. We compared angiographic and clinical outcomes in patients with occlusions of the M1 segment of the middle cerebral artery treated with mechanical thrombectomy using extra-LB-DAC versus LB-DAC in combination with stent-retrievers. METHODS: We analyzed consecutive patients with M1 occlusion included in the ROSSETTI registry treated with non-balloon guide catheter combined LB-DAC/stent-retriever thrombectomy between June 2019 and April 2022. We compared demographics, baseline clinical variables, procedural variables, angiographic outcomes, and clinical outcomes [National Institute of Health Stroke Scale score at 24 h (24h-NIHSS) and modified Rankin scale score at 3 months] between patients treated with extra-LB-DAC (Sofia Plus, MIVI Q6, Catalyst7; inner diameter, 0.068″-0.070″) versus LB-DAC (Sofia 5F, MIVI Q5, Catalyst 6; inner diameter, 0.055″-0.064″). Primary outcome was the first-pass effect (FPE) rate, defined as near-complete/complete reperfusion (mTICI 2c-3) after a single pass of the device. RESULTS: We included 324 patients (extra-LB-DAC, 185, 57.1% patients). Demographics, clinical data, and clinical outcomes were similar between the two groups; however, there was a trend towards improvement in National Institute of Health Stroke Scale score at 24 h (24h-NIHSS) in the cohort treated with extra-LB-DAC 9 points (IQR 4;16 points) vs. 12 points (IQR 4;18 points, P = 0.083). Patients treated with extra-LB-DAC had higher FPE rate (47% vs. 30.9%; P = 0.003) and higher modified FPE (mTICI ≥ 2b after a single pass) rate (65.9% vs 46.8%; P = 0.001). The use of extra-LB-DAC was an independent factor in predicting FPE (odds ratio 1.982, 95% confidence interval 1.250-3.143, P = 0.004). CONCLUSION: Our results suggest that in combined LB-DAC/stent-retriever thrombectomy, a larger aspiration catheter inner diameter is associated with higher rates of FPE and mFPE.

The Effect of Number of Gait Cycles on Principal Activation Extraction.

To cope with the high intra-subject variability of muscle activation intervals, a large amount of gait cycles is necessary to clearly document physiological or pathological muscle activity patterns during human locomotion. The Clustering for Identification of Muscle Activation Pattern (CIMAP) algorithm has been proposed to help clinicians obtaining a synthetic and clear description of normal and pathological muscle functions in human walking. Moreover, this algorithm allows the extraction of Principal Activations (PAs), defined as those muscle activations that are strictly necessary to perform a specific task and occur in every gait cycle. This contribution aims at assessing the impact of the number of gait cycles on the extraction of the PAs. Results demonstrated no statistically significant differences between PAs extracted considering different numbers of gait cycles, revealing, on average, similarity values higher than 0.88.Clinical Relevance-This contribution demonstrates the potential applicability of the CIMAP algorithm to the analysis of subjects affected by neurological disorders, for whom the assessment of motor functions may be of the uttermost importance and only a reduced number of gait cycles can be acquired.

Multicenter Retrospective Registry of Anterior Communicating Artery Aneurysms with Endovascular Therapy (MACAARET): safety and efficacy study according to morphological considerations and spatial orientations.

AIM: To analyse the safety and efficacy parameters of endovascular treatment of anterior communicating artery (ACoA) aneurysms, according to their morphological considerations and three-dimensional orientation in a multicentric registry. MATERIALS AND METHODS: A retrospective analysis was undertaken of a prospective database of consecutive patients that underwent endovascular embolisation for ACoA aneurysm in four high-volume neuroradiology interventional departments. The study has been registered in ClinicalTrial.gov. Data were collected regarding the clinico-demographic variables of the patients, anatomical variations of the circle of Willis, morphological considerations and spatial orientation of ACoA aneurysms were recorded. Safety and efficacy variables were also recorded. Associations between anatomical variations of the circle of Willis, morphological considerations, and spatial orientation of the ACoA aneurysms and safety and efficacy variables were assessed. RESULTS: Data from 122 consecutive patients were collected in the MACAARET study (mean age (±SD) was 55 (±14) and 50.8% (62/122) were male). One hundred and five patients (86.1%) presented with subarachnoid haemorrhage (SAH). ACoA aneurysms with a neck size of >4 mm had less chance of having successful endovascular treatment than those of ≤4 mm (19.8% versus 46.7%; p=0.002) and were also more likely to recanalise during follow-up (61.5% versus 19.5%; p=0.003). Moreover, ACoA aneurysms with an aspect ratio of >1.7 had more chance of having immediate therapeutic success than those with a ratio of ≤1.7 (70.7% versus 44.8%; p=0.012). There were no other associations between the anatomical variables of the ACoA aneurysms and the safety-efficacy variables. CONCLUSION: ACoA aneurysms are suitable for both endovascular and microsurgical approaches, but more data are required to determine which is the best approach regarding the morphological and spatial orientation of the aneurysm and the anatomical variations of the circle of Willis.

Use of intracranial stent as rescue therapy after mechanical thrombectomy failure-9-year experience in a comprehensive stroke centre.

PURPOSE: There is no established rescue treatment in patients with mechanical thrombectomy (MT) failure. Our aim is to analyse whether the use of an intracranial stent improves prognosis in these patients. METHODS: Retrospective analysis of a prospective cohort of patients with ischemic stroke due to middle cerebral artery occlusion (MCA) or distal intracranial carotid artery (ICA) occlusion, from September 2009 to April 2019 in our comprehensive stroke care centre. Patients with MT failure were identified and dichotomized into two groups according to whether or not an intracranial stent was implanted. We analysed clinical outcomes in both groups. RESULTS: There was MT failure in 60 patients (14%) of the 433 with large vessel occlusion in distal ICA and proximal MCA. A stent was placed in 20 of them (33.3%). Compared to patients without rescue stenting, they showed better rates of independence at 3 months (mRS ≤ 2) 45% vs 2.5% (p < 0.001) and lower mortality 15% vs 50% (p = 0.009), maintaining statistical significance after multivariate analysis, without a significant increase of the rate of symptomatic intracranial haemorrhage (p = 0.209). CONCLUSION: Placement of an intracranial stent as rescue therapy after MT failure was associated with better clinical outcome without significant increase in haemorrhagic complications. We believe that this procedure should be appraised in these patients.

Dual SAVE technique for mechanical thrombectomy rescue on MCA bifurcation clots.

The Stent retriever Assisted Vacuum-locked Extraction (SAVE) technique in mechanical thrombectomy consists of the simultaneous use of a stent retriever and a distal aspiration catheter, with the removal of both as a unit when performing the thrombectomy pass. This is a safe procedure that provides a high rate of first-pass reperfusion.1 In the distal M1 segment of the middle cerebral artery (MCA) occlusions, with the distal portion of the clot extending to the upper and lower MCA branches, mechanical thrombectomy can be challenging since the thrombus is not fully trapped, with risk of distal clot migration to the branch in which the retriever is not placed. In these cases the double stent-retriever technique has been described as a rescue strategy.2-4 We describe a case of the combined use of SAVE and double stent-retriever techniques as a rescue strategy in a patient with tandem occlusion of the proximal internal carotid artery and distal MCA-the D-SAVE technique. (video 1).

Usefulness of CT angiography for characterizing cerebral arteriovenous malformations presenting as hemorrhage: comparison with digital subtraction angiography. / Utilidad de la angio-TC para la caracterización de malformaciones arteriovenosas cerebrales con presentación hemorrágica comparada con la angiografía por sustracción digital.

OBJECTIVE: To compare the usefulness of CT angiography against the gold standard, digital subtraction angiography (DSA), in the characterization of cerebral arteriovenous malformations (AVM) that present with bleeding. MATERIAL AND METHODS: We retrospectively analyzed patients with intracranial bleeding due to an AVM who were included in a prospective database in the period comprising January 2007 through December 2012. We reviewed radiologic variables such as the characteristics of the AVM (size, location, presence of deep venous drainage), involvement of eloquent areas, and the presence of associated aneurysms. Two neuroradiologists blinded to clinical and radiological information analyzed the CT and DSA in consensus. RESULTS: A total of 22 patients were included in the study. CT angiography correctly classified 15 of the 16 cases of AVM measuring less than 3cm (93.75% sensitivity). All cases of deep venous drainage and all those located in eloquent areas were correctly detected (100% sensitivity). The presence of any type of aneurysm related with the AVM was detected in 13 of 15 cases (86.6% sensitivity); 7 of 9 of the intranidal aneurysms were detected (77.78% sensitivity), as were 6 of the 9 flow aneurysms (66.67% sensitivity). CONCLUSION: CT angiography is highly sensitive in the characterization of cerebral AVMs measuring less than 3cm, of those located in eloquent areas, and of those with deep venous drainage; it is also highly sensitive in detecting aneurysms related with AVMs. However, CT angiography is less sensitive in detecting intranidal and flow aneurysms related with AVMs.

Diagnostic performance of FDG-PET/CT of post-transplant lymphoproliferative disorder and factors affecting diagnostic yield.

PURPOSE: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ and hematopoietic stem cell transplantation, requiring a timely and accurate diagnosis. In this study, we evaluated the diagnostic performance of FDG-PET/CT in patients with suspected PTLD and examined if lactate dehydrogenase (LDH) levels, Epstein-Barr virus (EBV) load, or timing of FDG-PET/CT relate to detection performance of FDG-PET/CT. METHODS: This retrospective study included 91 consecutive patients with clinical suspicion of PTLD and a total of 97 FDG-PET/CT scans within an 8-year period. Pathology reports and a 2-year follow-up were used as the reference standard. Diagnostic performance of FDG-PET/CT for detection of PTLD as well as logistic regression analysis for factors expected to affect diagnostic yield were assessed. RESULTS: The diagnosis of PTLD was established in 34 patients (35%). Fifty-seven FDG-PET/CT scans (59%) were true negative, 29 (30%) were true positive, 6 (6%) false positive, and 5 (5%) false negative. Sensitivity of FDG-PET/CT for the detection of PTLD was 85%, specificity 90%, positive predictive value 83%, and negative predictive value 92%, with good inter-observer variability (k = 0.78). Of the parameters hypothesized to be associated with a true positive FDG-PET/CT result for the diagnosis of PTLD, only LDH was statistically significant (OR 1.03, p = 0.04). CONCLUSION: FDG-PET/CT has a good diagnostic performance in patients suspected of PTLD, with a good inter-observer agreement. Only LDH levels seemed to influence the detection performance of FDG-PET/CT. EBV-DNA load and timing of FDG-PET/CT after transplantation did not affect FDG-PET/CT diagnostic yield.

Relationship between semiquantitative 18F-fluorodeoxyglucose positron emission tomography metrics and necrosis in classical Hodgkin lymphoma.

Semiquantitative 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) parameters have been proposed as prognostic markers in classical Hodgkin lymphoma (cHL). In non-Hodgkin lymphoma necrosis as assessed by 18F-FDG PET or computed tomography (CT) (necrosisvisual) correlates with an adverse prognosis. We investigated whether semiquantitative 18F-FDG PET metrics correlate with necrosisvisual, determined the incidence of necrosisvisual and explored the prognostic impact of these factors in cHL. From 87 cHL cases treated with ABVD, (escalated) BEACOPP or CHOP chemotherapy between 2010 and 2017, 71 had both a NEDPAS/EARL accredited 18F-FDG PET and a contrast enhanced CT scan. Semiquantitative 18F-FDG PET parameters were determined using Hermes Hybrid 3D software. Necrosisvisual, defined by photopenic tumor areas on 18F-FDG PET and attenuation values between 10 and 30 Hounsfield units (HUs) on CT, was assessed blinded to outcome. Univariate Cox regression survival analyses of progression free survival (PFS) were performed. Necrosisvisual was observed in 18.3% of cHL patients. Bulky disease (tumor mass >10 cm in any direction) (P = 0.002) and TLG (P = 0.041) but no other semiquantitative parameters were significantly associated with necrosisvisual. In exploratory univariate survival analysis for PFS the covariates IPS, bulky disease, MTV and TLG were prognostic, while necrosisvisual was not.

Asymmetry Index in Muscle Activations.

Gait asymmetry is typically evaluated using spatio-temporal or joint kinematics parameters. Only a few studies addressed the problem of defining an asymmetry index directly based on muscle activity, extracting parameters from surface electromyography (sEMG) signals. Moreover, no studies used the extraction of the muscle principal activations (activations that are necessary for accomplishing a specific motor task) as the base to construct an asymmetry index, less affected by the variability of sEMG patterns. The aim of this paper is to define a robust index to quantitatively assess the asymmetry of muscle activations during locomotion, based on the extraction of the principal activations. SEMG signals were analyzed combining statistical gait analysis (SGA) and a clustering algorithm that allows for obtaining the muscle principal activations. We evaluated the asymmetry levels of four lower limb muscles in: (1) healthy subjects of different ages (children, adults, and elderly); (2) different populations of orthopedic patients (adults with megaprosthesis of the knee after bone tumor resection, elderly subjects after total knee arthroplasty, and elderly subjects after total hip arthroplasty); and (3) neurological patients (children with hemiplegic cerebral palsy and elderly subjects affected by idiopathic normal pressure hydrocephalus). The asymmetry index obtained for each pathological population was then compared to that of age-matched controls. We found asymmetry levels consistent with the expected impact of the different pathologies on muscle activation during gait. This suggests that the proposed index can be successfully used in clinics for an objective assessment of the muscle activation asymmetry during locomotion.

Characterization of Physicians Workload in a Reference Center for the Treatment of Thrombotic and Bleeding Disorders.

Heavy workloads in healthcare have been often associated to adverse clinical outcomes. To reduce workloads, an optimal scheduling of clinical staff resources is not enough, but particular attention must be payed to work organization and task characteristics. Moreover, interruptions during the clinical practice contribute to increase perceived workloads. In this study we analyzed and characterized the physicians' workload in an Italian center for the treatment of thrombotic and bleeding disorders. First, all clinical and administrative processes performed in the center were analyzed by means of two process modelling tools. Then, the quantification of the physicians' workload and the characterization of interruptions during practice were conducted. From our results it emerged that the task that mainly impacts on the workload is ambulatory care (42% of total workload) while interruptions produce a delay of almost 15 minutes per day and mainly occur during visits. Including all activities, the total daily workload per physician was 8 hours on average. In this time breaks were not taken into account. Concluding, from our analysis it is evident that the physicians' workload in the analyzed center is heavy and interruptions represent a source of delay in the workflow, that impact the physicians' workload.

Pediatric Brain Tissue Segmentation from MRI using Clustering: a Preliminary Study.

Brain Tissue Segmentation (BTS) in young children and neonates is not a trivial task due to peculiar characteristics of the developing brain. The aim of this study is to present the preliminary results of new atlas-free BTS (afBTS) algorithm of MR images for pediatric applications, based on clustering. The algorithm works on axial T1, T2 and FLAIR sequences. First, the Cerebrospinal Fluid (CSF) is identified using the Region Growing algorithm. The remaining voxels are processed with the k-means algorithm in order to separate White Matter (WM) and Grey Matter (GM). The afBTS algorithm was applied to a population of 13 neonates; the segmentations were evaluated by two expert pediatric neuroradiologists and compared with an atlas-based algorithm. The results were promising: afBTS allowed reconstruction of WM and CSF with an image quality comparable to the reference of standard while lower segmentation quality was obtained for the GM segmentation.

Erratum: Chiral Effective Field Theory Predictions for Muon Capture on Deuteron and

This corrects the article DOI: 10.1103/PhysRevLett.108.052502.

Complete Genome Sequence of Bovine Viral Diarrhea Virus Subgenotype 2a Strain CN10.2015.821, Isolated in Piedmont, Italy.

We sequenced the complete genome of noncytopathic bovine viral diarrhea virus (BVDV) type 2 strain CN10.2015.821. It belongs to the subgenotype 2a, and it was isolated from an immunotolerant and persistently infected calf identified during a serological investigation. The complete genome is composed of 12,273 nucleotides, organized as one open reading frame encoding 3,897 amino acids.

Influence of pre-processing in the extraction of muscle synergies during human locomotion.

The extraction of muscle synergies in human locomotion may be biased by the kind of pre-processing applied to electromyographic (EMG) data. The aim of this contribution is to analyze the differences in the muscle synergies extracted using a standard pre-processing procedure and a new procedure. The new procedure is based on the selection of the muscle's principal activations (necessary actuations of the muscle to accomplish its specific biomechanical task during gait), discarding secondary activations (with an auxiliary function in motor control). EMG signals were recorded from 12 muscles of a healthy volunteer who was asked to walk, at self-selected pace, for 5 minutes. A dataset of 193 gait cycles was collected and divided into 19 epochs of 10 concatenated gait cycles. The application of the new pre-processing procedure provided 5 instead of 6 muscle synergies accurately reconstructing the original EMG data matrix, and clearer and more stable neural activation commands. The new preprocessing procedure may be easily extended to the extraction of muscle synergies in other cyclic movements, such as running, stair climbing, cyclo-ergometer exercising, and swimming.

Rabbit dietary supplementation with pale purple coneflower. 2. Effects on the performances, bacterial community, blood parameters and immunity of growing rabbits.

Echinacea pallida (EPAL), a herbaceous flowering plant with immunomodulatory properties, has been chosen to determine the pre- and post-supplementary effects on the growth performances, bacterial community, blood parameters and immunity of growing rabbits. The same Grimaud does (14-week-old) from the studied in the first part of this study were randomly divided into two groups (n=50/group). The first group was fed a basal diet without supplementation (Control group, C) while the another group was fed a basal diet supplemented with 3 g EPAL/kg diet (Echinacea group, E). From the second parturition, 80 weaned kits (40 from the C does and 40 from the E does) were randomly assigned to four groups of 20 animals each and were fed a growing commercial diet supplemented with or without a 3 g EPAL/kg diet: the CC group (rabbits from the C does fed the control diet), CE group (rabbits from the C does fed the supplemented diet), EC (rabbits from the E does fed the control diet) and EE group (rabbits from the E does fed the supplemented diet). The dietary EPAL treatment did not affect the growth performance. Ten fattening rabbits from each group were selected to evaluate the bacterial community and blood parameters, while the remaining rabbits (n=10/group) were used to study phagocytosis and the humoral immune response. The variability was evaluated from hard faeces at 35, 49 and 89 days, and the caecal content at 89 days. The variability of the bacterial community of the EE group was higher than that of the other groups. The phagocytic activity was higher in the CE and EE groups than in the CC and EC ones (30.9 and 29.7 v. 21.2 and 21.8%; P<0.05), whereas no statistically significant difference was observed for the blood parameters or humoral immune response against vaccination (rabbit haemorrhagic disease virus) at 95 days old which the serum was collected at 88, 102, 109, 116 and 123 days old. In conclusion, no impact of EPAL dietary supplementation has been observed on the growth performances, bacterial community, blood parameters or humoral immune responses in growing rabbits, except for an increase in phagocytic activities.

Radiation Doses in Patient Eye Lenses during Interventional Neuroradiology Procedures.

BACKGROUND AND PURPOSE: Eye lenses are among the most sensitive organs to x-ray radiation and may be considered at risk during neurointerventional radiology procedures. The threshold dose to produce eye lens opacities has been recently reduced to 500 mGy by the International Commission on Radiologic Protection. In this article, the authors investigated the radiation doses delivered to patients' eyes during interventional neuroradiology procedures at a university hospital. MATERIALS AND METHODS: Small optically stimulated luminescence dosimeters were located over patients' eyes during 5 diagnostic and 31 therapeutic procedures performed in a biplane x-ray system. Phantom measurements were also made to determine the level of radiation to the eye during imaging runs with conebeam CT. RESULTS: The left eye (located toward the lateral C-arm x-ray source) received a 4.5 times greater dose than the right one. The average dose during embolization in the left eye was 300 mGy, with a maximum of 2000 mGy in a single procedure. The patient who received this maximum eye dose needed 6 embolization procedures to treat his high-volume AVM. If one took into account those 6 embolizations, the eye dose could be 2-fold. Sixteen percent of the embolizations resulted in eye doses of >500 mGy. CONCLUSIONS: A relevant fraction of patients received eye doses exceeding the threshold of 500 mGy. A careful optimization of the procedures and follow-up of these patients to evaluate potential lens opacities should be considered.

Cloning, expression, and antigenic characterization of recombinant protein of Mycoplasma gallisepticum expressed in Escherichia coli.

Mycoplasma gallisepticum (MG) is a member of the most important avian mycoplasmas, causing chronic respiratory disease in chickens and leading to important economic losses in the poultry industry. Recombinant technology represents a strategic approach used to achieve highly reliable and specific diagnostic tests in veterinary diseases control: in particular this aspect is crucial for confirming mycoplasma infection and for maintaining mycoplasma-free breeder flocks. In this study, we identified a component of the pyruvate dehydrogenase dihydrolipoamide acetyltransferase (i.e., E2) protein by 2-dimensional electrophoresis (2-DE), characterized it in immunoblotting assays, and analyzed its recombinant (r-E2) in a rec-ELISA test. For full-length protein expression in Escherichia coli (EC) a point mutation was introduced. A rabbit antiserum produced against r-E2 was tested in a Western Blot using different samples of Mycoplasma species. The results showed the applicability of site-directed mutagenesis, with a good yield of the r-E2 after purification. Also, anti-E2 serum reacted with all the tested MG strains showing no cross reaction with other mycoplasmas. The developed E2 ELISA test was capable of detecting MG antibodies in the sera examined. Those results demonstrate the antigenic stability of the E2 protein which could represent a recombinant antigen with potential diagnostic applications.

Developing medical device software in compliance with regulations.

In the last decade, the use of information technology (IT) in healthcare has taken a growing role. In fact, the adoption of an increasing number of computer tools has led to several benefits related to the process of patient care and allowed easier access to social and health care resources. At the same time this trend gave rise to new challenges related to the implementation of these new technologies. Software used in healthcare can be classified as medical devices depending on the way they are used and on their functional characteristics. If they are classified as medical devices they must satisfy specific regulations. The aim of this work is to present a software development framework that can allow the production of safe and high quality medical device software and to highlight the correspondence between each software development phase and the appropriate standard and/or regulation.