Search

Purpose: Intraoperative radiation therapy with electrons (IOERT) may represent a viable choice for partial breast reirradiation after repeat quadrantectomy for local recurrence (LR) for primary breast cancer (BC) in lieu of mastectomy., Methods and Materials: A database collecting data on partial breast reirradiation with IOERT from 8 Italian centers was set up in 2016 to 2018, providing data on cumulative incidence (CumI) of second LR and survival with a long follow-up., Results: From 2002 to 2015, 109 patients underwent the conservative retreatment. The median primary BC first LR interval was 11.1 years (range, 2.4-27.7). The median first LR size was 0.9 cm (range, 0.3-3.0), and 43.6% cases were luminal A. Median IOERT dose was 18 Gy (range, 12-21), and median collimator diameter was 4 cm (range, 3-6). Median follow-up duration was 11.7 years (IQR, 7.7-14.6). The second LR CumI was 12.2% (95% CI, 6.8%-19.2%) at 5 years and 32.3% at 10 years (95% CI, 22.8%-42.2%), occurring in the same site as the first LR in about half of the cases. Human epidermal growth factor receptor 2 status and collimator size were independent LR predictors. The 5- and 10-year overall survival rates were 95.2% and 88.3%, respectively, whereas 5- and 10-year BC-specific survival rates were 98% and 94.5%, respectively. The development of a second LR significantly reduced BC-specific survival (hazard ratio, 9.40; P < .001). Grade ≥3 fibrosis rate was 18.9%. Patient-reported cosmesis was good/excellent in 59.7% of the cases., Conclusions: Second LR CumI was within the range of the literature but higher than expected, opening questions on radiation field extension and fractionation schedule. Because a second LR worsened the outcome, salvage modality must be carefully planned., Competing Interests: Disclosures The Division of Radiation Oncology of the European Institute of Oncology (IEO) received research funding from the Italian Association for Cancer Research (AIRC), Fondazione Istituto Europeo di Oncologia-Centro Cardiologico Monzino (IEO-CCM), Accuray, and Ion Beam Applications (IBA), all outside the current project. Barbara Alicja Jereczek-Fossa received speaker fees from Bayer, Accuray, Astellas, IBA, Ipsen, Astra Zeneca, Tecnologie Avanzate, Recordati, and Novartis; participated in the Advisory Board of Accuray, Bayer, and Seagen, all outside the current project. Maria Cristina Leonardi received a speakers fee from Accuray, and Samantha Dicuonzo received a speakers fee from Accuray Asia (all outside the current project). The remaining authors declare no conflicts of interest that are relevant to the content of this article., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: MITO-RT3/RAD (NCT04593381) is a prospective multicenter phase 2 trial designed to assess the effectiveness and safety of stereotactic body radiation therapy (SBRT) in patients who received diagnoses of oligometastatic ovarian cancer. In this report, we provide the results of the trial in the setting of lymph node disease., Methods and Materials: The primary endpoint was the complete response (CR) rate, secondary endpoints included local control (LC), progression-free survival (PFS), overall survival, treatment-free interval, and toxicity rates. The sample size was based on a previous study reporting an average 70.0% CR with SBRT. The study was powered to detect an improvement in the CR rate from 70.0% to 85.0%, with an α error of 0.05 (one-side) and a β error of 0.1., Results: The study met its primary endpoint of a statistically significant improvement in CR. One hundred thirty-five patients with 249 lesions were enrolled across 15 institutions from May 2019 to November 2023. CRs were observed in 194 lesions (77.9%), partial responses in 40 (16.1%), stable disease in 14 (5.6%), and progressive disease in 1 lesion (0.4%). The objective response rate was 94%, with an overall clinical benefit rate of 99.6%. CR lesions exhibited a significantly higher LC rate than partial or not responding lesions (12-month LC: 92.7% vs 63.1%, P < .001). The 12-month actuarial rates for PFS and for overall survival were 36.6% (CR, 38.3% vs not-CR, 18.8%; P, .022) and 97.2% (CR, 97.8% vs not-CR, 93.8%; P, .067), respectively. The 12-month actuarial rate for treatment-free interval was 52.7% (CR, 58.4% vs not-CR, 24.4%; P, .004). CR was substantially associated with higher PFS (P, .036) and treatment-free interval (P, .006) rates in the univariate analysis. Twenty-three patients (17.0%) experienced mild acute toxicity. Late toxicity was reported in 9 patients (6.7%), mostly grade 1., Conclusions: This trial confirms the efficacy of ablative SBRT, with minimal toxicity observed. SBRT offered a high CR rate, promising long-term outcomes, and a significant systemic therapy-free survival period for complete responders., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Poly (ADP-ribose) polymerase inhibitors (PARPi) have become a new standard of care for the maintenance treatment of advanced epithelial ovarian cancer. This study aims to evaluate the efficacy and safety of combining stereotactic body radiotherapy with PARPi continuation as a strategy to treat ovarian cancer oligoprogression on PARPi., Methods: This is a multicenter retrospective study including ovarian cancer patients treated with stereotactic body radiotherapy and PARPi continuation for oligoprogression under PARPi maintenance therapy between June 2012 and May 2023 in three Italian centers. PARPi treatment was continued until further disease progression or unacceptable toxicity. The primary endpoint was the next-line systemic therapy-free interval. The Kaplan-Meier method was used to assess local control, progression-free survival, and overall survival. Univariate and multivariate Cox regression analyses were performed to evaluate potential clinical outcomes predictors., Results: 46 patients were included, with a total of 89 lesions treated over 63 radiotherapy treatments. Lymph nodes were the most frequently treated lesions (80, 89.9%), followed by visceral lesions (8, 9%) and one case with a bone lesion (1.1%). Median follow-up was 25.9 months (range 2.8-122). The median next-line systemic therapy-free interval was 12.4 months (95% CI 8.3 to 19.5). A number of prior chemotherapy lines greater than five was significantly associated with a reduced next-line systemic therapy-free interval (HR 3.21, 95% CI 1.11 to 9.32, p=0.032). At the time of analysis, 32 (69.6%) patients started a new systemic therapy regimen, while 14 (30.4%) remained on the PARPi regimen. The 2-year progression-free survival, local failure-free survival, and overall survival rates were 10.7%, 78.1%, and 76.5%, respectively. Four patients (8.7%) experienced acute toxicity with G1 gastrointestinal events., Conclusion: Stereotactic body radiotherapy combined with PARPi continuation may be an effective and safe strategy for managing ovarian cancer patients with oligoprogression on PARPi maintenance therapy. Prospective research is warranted to shed more light on this approach., Competing Interests: Competing interests: BAJ-F has received speakers fees from Roche, Bayer, Janssen, Carl Zeiss, Ipsen, Accuray, Astellas, Elekta, and IBA Astra Zeneca, all outside the current project., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Glycoconjugation is a well-established technology for vaccine development: linkage of the polysaccharide (PS) antigen to an appropriate carrier protein overcomes the limitations of PS T-independent antigens, making them effective in infants and providing immunological memory. Glycoconjugate vaccines have been successful in reducing the burden of different diseases globally. However, many pathogens still require a vaccine, and many of them display a variety of glycans on their surface that have been proposed as key antigens for the development of high-valency glycoconjugate vaccines. CDAP chemistry represents a generic conjugation strategy that is easily applied to PS with different structures. This chemistry utilizes common groups to a large range of PS and proteins, e.g., hydroxyl groups on the PS and amino groups on the protein. Here, new fast analytical tools to study CDAP reaction have been developed, and reaction conditions for PS activation and conjugation have been extensively investigated. Mathematical models have been built to identify reaction conditions to generate conjugates with wanted characteristics and successfully applied to a large number of bacterial PSs from different pathogens, e.g., Klebsiella pneumoniae , Salmonella Paratyphi A, Salmonella Enteritidis, Salmonella Typhimurium, Shighella sonnei and Shigella flexneri . Furthermore, using Salmonella Paratyphi A O-antigen and CRM 197 as models, a design of experiment approach has been used to study the impact of conjugation conditions and conjugate features on immunogenicity in rabbits. The approach used can be rapidly extended to other PSs and accelerate the development of high-valency glycoconjugate vaccines.

The work investigates the implementation of personalized radiotherapy boluses by means of additive manufacturing technologies. Boluses materials that are currently used need an excessive amount of human intervention which leads to reduced repeatability in terms of dosimetry. Additive manufacturing can solve this problem by eliminating the human factor in the process of fabrication. Planar boluses with fixed geometry and personalized boluses printed starting from a computed tomography scan of a radiotherapy phantom were produced. First, a dosimetric characterization study on planar bolus designs to quantify the effects of print parameters such as infill density and geometry on the radiation beam was made. Secondly, a volumetric quantification of air gap between the bolus and the skin of the patient as well as dosimetric analyses were performed. The optimization process according to the obtained dosimetric and airgap results allowed us to find a combination of parameters to have the 3D-printed bolus performing similarly to that in conventional use. These preliminary results confirm those in the relevant literature, with 3D-printed boluses showing a dosimetric performance similar to conventional boluses with the additional advantage of being perfectly conformed to the patient geometry., (© 2024. The Author(s).)

Purpose: To report the results involving post-operative interventional radiotherapy (POIRT) in a homogenous cohort of patients affected by keloid and treated at a single institution with the same fractionation schedule., Patients and Methods: Inclusion criteria were: surgery with a histopathological diagnosis of keloid, subsequent high-dose rate interventional radiotherapy (HDR-IRT)-12 Gy in 4 fractions (3 Gy/fr) twice a day-and follow-up period ≥ 24 months., Results: One-hundred and two patients and a total of 135 keloids were eligible for the analyses. Median follow-up was 64 [IQR: 25-103] months. Thirty-six (26.7%) recurrences were observed, 12-months and 36-months cumulative incidence of recurrence were 20.7% (95% CI 12.2-28.5) and 23.8% (95% CI 14.9-31.7) respectively. History of spontaneous keloids (HR = 7.00, 95% CI 2.79-17.6, p < 0.001), spontaneous cheloid as keloid cause (HR = 6.97, 95% CI 2.05-23.7, p = 0.002) and sternal (HR = 10.6, 95% CI 3.08-36.8, p < 0.001), ear (HR = 6.03, 95% CI 1.71-21.3, p = 0.005) or limb (HR = 18.8, 95% CI 5.14-68.7, p < 0.001) keloid sites were significantly associated to a higher risk of recurrence., Conclusions: The findings support the use of surgery and POIRT as an effective strategy for controlling keloid relapses. Further studies should focus on determining the optimal Biologically Effective Dose and on establishing a scoring system for patient selection., (© 2024. The Author(s).)

Objectives: This single-centre prospective randomised controlled study aimed to investigate the effectiveness of dignity therapy on spiritual well-being, demoralisation and dignity-related distress compared with standard palliative care., Methods: A total of 111 terminally ill hospice patients were randomly allocated to one of two groups: dignity therapy plus standard palliative care (intervention group) or standard palliative care alone (control group). The main outcomes were meaning, peace, faith, loss of meaning and purpose, distress and coping ability, existential distress, psychological distress and physical distress. Assessments were conducted at baseline, 7-10 and 15-20 days., Results: Following randomisation, 11 dropped out before baseline assessment and 33 after post-treatment assessment. A total of 67 patients completed the study, 35 in the experimental group and 32 in the control group. Repeated measures general linear model showed significant differences between groups on peace and psychological distress over time, but not on existential distress, physical distress, meaning and purpose, distress and coping ability, meaning and faith. Specifically, patients in the dignity therapy intervention maintained similar levels of peace from baseline to follow-up, whereas patients in the control group significantly declined in peace during the same time period. Moreover, psychological distress significantly decreased from pretreatment to post-treatment in the intervention group and increased in the control group., Conclusions: Dignity therapy may be an effective intervention in maintaining sense of peace for terminally ill patients. The findings of our study are of relevance in palliative care and suggest the potential clinical utility of this psychological intervention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Several psychological dimensions influence the psychological adjustment of terminally ill cancer patients' caregivers, during the end-of-life phase. The present study explored the associations between attachment styles, mentalization, preparedness for death, and the severity of pre-loss grief symptoms in 102 caregivers of terminal cancer patients. The results of the network analysis showed that insecure attachment dimensions were positively associated with several central pre-loss grief symptoms. Mentalization and preparedness for death showed negative associations with several pre-loss grief symptoms. Interestingly, bitterness showed a negative association with need for approval and a positive association with mentalization. The results provided insight into the grieving process for palliative care providers to implement effective caregiver support interventions.

The foot is responsible for the bodyweight transfer to the ground, while adapting to different terrains and activities. Despite this fundamental role, the knowledge about the foot bone intrinsic kinematics is still limited. The aim of the study is to provide a quantitative and systematic description of the kinematics of all bones in the foot, considering the full range of dorsi/plantar flexion and pronation/supination of the foot, both in weightbearing and nonweightbearing conditions. Bone kinematics was accurately reconstructed for three specimens from a series of computed tomography scans taken in weightbearing configuration. The ground inclination was imposed through a set of wedges, varying the foot orientation both in the sagittal and coronal planes; the donor body-weight was applied or removed by a cable-rig. A total of 32 scans for each foot were acquired and segmented. Bone kinematics was expressed in terms of anatomical reference systems optimized for the foot kinematic description. Results agree with previous literature where available. However, our analysis reveals that bones such as calcaneus, navicular, intermediate cuneiform, fourth and fifth metatarsal move more during foot pronation than flexion. Weightbearing significantly increase the range of motion of almost all the bone. Cuneiform and metatarsal move more due to weightbearing than in response to ground inclination, showing their role in the load-acceptance phase. The data here reported represent a step toward a deeper understanding of the foot behavior, that may help in the definition of better treatment and medical devices, as well as new biomechanical model of the foot., (© 2023 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Background and Purpose: Radiomics enables the mining of quantitative features from medical images. The influence of the radiomic feature extraction software on the final performance of models is still a poorly understood topic. This study aimed to investigate the ability of radiomic features extracted by two different radiomic platforms to predict clinical outcomes in patients treated with radiosurgery for brain metastases from non-small cell lung cancer. We developed models integrating pre-treatment magnetic resonance imaging (MRI)-derived radiomic features and clinical data., Materials and Methods: Pre-radiotherapy gadolinium enhanced axial T1-weighted MRI scans were used. MRI images were re-sampled, intensity-shifted, and histogram-matched before radiomic extraction by means of two different platforms (PyRadiomics and SOPHiA Radiomics). We adopted LASSO Cox regression models for multivariable analyses by creating radiomic, clinical, and combined models using three survival clinical endpoints (local control, distant progression, and overall survival). The statistical analysis was repeated 50 times with different random seeds and the median concordance index was used as performance metric of the models., Results: We analysed 276 metastases from 148 patients. The use of the two platforms resulted in differences in both the quality and the number of extractable features. That led to mismatches in terms of end-to-end performance, statistical significance of radiomic scores, and clinical covariates found significant in combined models., Conclusion: This study shed new light on how extracting radiomic features from the same images using two different platforms could yield several discrepancies. That may lead to acute consequences on drawing conclusions, comparing results across the literature, and translating radiomics into clinical practice., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Metal components of hip prostheses cause severe artifacts in CT images, influencing diagnostic accuracy. Metal artifact reduction (MAR) software and virtual monoenergetic reconstructions on dual-energy CT (DECT) systems are possible solutions that should be considered. In this study, we created a customized adjustable phantom to quantify the severity of artifacts on periprosthetic tissues (cortical and spongious bone, soft tissues) for hip prostheses. The severity of artifacts was classified by different thresholds of deviation from the CT numbers for reference objects not affected by artifacts. The in vitro setup was applied on four unilateral and three bilateral configurations of hip prostheses (made of titanium, cobalt, and stainless steel alloys) with a DECT system, changing the energy of virtual monoenergetic reconstructions, with and without MAR. The impact of these tools on the severity of artifacts was scored, looking for the best scan conditions for the different configurations. For titanium prostheses, the reconstruction at 110 keV, without MAR, always minimized the artifacts. For cobalt and stainless-steel prostheses, MAR should always be applied, while monoenergetic reconstruction alone did not show clear advantages. The available tools for reducing metal artifacts must therefore be applied depending on the examined prosthetic configuration.

Cone-beam CT (CBCT) scans now enable accurate measurements on foot skeletal structures with the advantage of observing these in 3D and in weight-bearing. Among the most common skeletal deformities, the varus/valgus of the hindfoot is the most complex to be represented, and a number of measure proposals have been published. This study aims to analyze and to compare these measurements from CBCT scans in a real clinical population with large such deformity. Ten patients with severe acquired adult flatfoot and indication for surgery underwent CBCT scans (Carestream, USA) while standing on that leg, before and after surgical correction. Corresponding 3D shape of each bone of the distal shank and hindfoot were defined (Materialise, Belgium). Six different techniques from the literature were used to calculate the varus/valgus deformity, i.e. the inclination of the hindfoot in the frontal plane of the shank. Standard clinical measurements by goniometers were taken for comparison. According to these techniques, and starting from a careful 3D reconstruction of the relevant foot skeletal structures, a large spectrum of measurements was found to represent the same hindfoot alignment angle. Most of them were very different from the traditional clinical measures. The assessment of the pre-operative valgus deformity and of the corresponding post-operative correction varied considerably. CBCT finally allows 3D assessment of foot deformities in weight-bearing. Measurements from the different available techniques do not compare well, as they are based on very different approaches. It is recommended to be aware of the anatomical and functional concepts behind these techniques before clinical and surgical conclusions., (© 2022. The Author(s).)

This work aims to test accuracy and comparability of 3D models of human skeletal fibulae generated by clinical CT and laser scanner virtual acquisitions. Mesh topology, segmentation and smoothing protocols were tested to assess variation among meshes generated with different scanning methods and procedures, and to evaluate meshes-interchangeability in 3D geometric morphometric analysis. A sample of 13 left human fibulae were scanned separately with Revolution Discovery CT dual energy (0.625 mm resolution) and ARTEC Space Spider 3D structured light laser scanner (0.1 mm resolution). Different segmentation methods, including half-maximum height (HMH) and MIA-clustering protocols, were compared to their high-resolution standard generated with laser-scanner by calculating topological surface deviations. Different smoothing algorithms were also evaluated, such as Laplacian and Taubin smoothing. A total of 142 semilandmarks were used to capture the shape of both proximal and distal fibular epiphyses. After Generalized Procrustes superimposition, the Procrustes coordinates of the proximal and distal fibular epiphyses were used separately to assess variation due to scanning methods and the operator error. Smoothing algorithms at low iteration do not provide significant variation among reconstructions, but segmentation protocol may influence final mesh quality (0.09-0.24 mm). Mean deviation among CT-generated meshes that were segmented with MIA-clustering protocol, and laser scanner-generated ones, is optimal (0.42 mm, ranging 0.35-0.56 mm). Principal component analysis reveals that homologous samples scanned with the two methods cluster together for both the proximal and distal fibular epiphyses. Similarly, Procrustes ANOVA reveals no shape differences between scanning methods and replicates, and only 1.38-1.43% of shape variation is due to scanning device. Topological similarities support the comparability of CT- and laser scanner-generated meshes and validate its simultaneous use in shape analysis with potential clinical relevance. We precautionarily suggest that dedicated trials should be performed in each study when merging different data sources prior to analyses., (© 2022 The Authors. Journal of Anatomy published by John Wiley & Sons Ltd on behalf of Anatomical Society.)

Fibular metric variations have revealed their potential in distinguishing between males and females; however the fibula remains scarcely analyzed in studies of sexual dimorphism. This work aims at investigating sexually dimorphic features in fibular proximal and distal epiphyses through geometric morphometrics methods. A total of 136 left fibulae, from two Italian and one South African identified skeletal collections were virtually acquired through CT and laser scanning and analyzed using geometric morphometric methods. Statistical analyses were performed on shape, form, and size variables. Results show that fibular epiphyses are smaller with narrower articular surfaces in females than in males in both extremities. Relevant sexual differences emerge in fibular form and size for the two Italian samples but not for the South African one, likely for its small sample size. Discriminant analysis on form principal components (PCs) offers accuracy above 80% when the samples are pooled, and reaches accuracy of 80-93% when the Italian samples are considered separately. However, our method on form PCs was not successful for the South African sample (50-53% accuracy), possibly due to the small sample size. These results show relevant morphological variation in relation to fibular form and size, with a degree of accuracy that indicates the utility of the present method for sexing human fibulae in both forensic and bioarchaeological contexts for Italian samples.

Background: A fully personalised combination of Gait Analysis (GA), including Ground Reaction Force (GRF), and patient-specific knee joint morphology has not yet been reported. This can provide valuable biomechanical insight in normal and pathological conditions. Abnormal knee varus results in medial knee condylar hyper-compression and osteoarthritis, which can be prevented by restoring proper condylar load distribution via High Tibial Osteotomy (HTO)., Research Question: This study was aimed at reporting on an original methodology, merging GA, GRF and Computer-Tomography (CT) to depict a patient-specific representation of the knee mechanical condition during locomotion. It was hypothesised that HTO results in a lateralized pattern of GRF with respect to the tibial plateau., Methods: Four patients selected for HTO received clinical, radiological and instrumental examinations, pre- and post-operatively at 6-month follow-up. GA was performed during level walking and more demanding motor tasks using a 9-camera motion-capture system, combined with two force platforms, and an established protocol. Additional skin markers were positioned around the tibial-plateau rim. Weight-bearing CT scans of the knee were collected while still wearing these markers. Proximal tibial and marker morphological models were reconstructed. The markers from CT reconstruction were then registered to the corresponding trajectories as tracked by GA data. Resulting registration matrices were used to report GRF vectors on the plane best matching the tibial-plateau model and the intersection paths were calculated., Results and Significance: The registration procedure was successfully executed, with a max registration error of about 3 mm. GRF intersection paths were found medially to the tibial plateau pre-op, and lateralized post-op, thus much closer to the knee centre, as expected after HTO. The exploitation of the present methodology offers personalised quantification of the original mechanical misalignment and of the effect of surgical correction which could enhance diagnostics and planning of HTO as well as other knee treatments., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: A complete definition of anatomical reference systems (ARS) for all bones of the foot and ankle complex is lacking. Using a morphological approach, we propose new ARS for these bones with the aim of being highly repeatable, consistent among individuals, clinically interpretable, and also suited for a sound kinematic description., Methods: Three specimens from healthy donors and three patients with flat feet were scanned in weight-bearing CT. The foot bones were segmented and ARS defined according to the proposed approach. To assess repeatability, intra class coefficients (ICC) were computed both intra- and inter-operator. Consistency was evaluated as the mean of the standard deviations of the ARS position and orientation, both within normal and flat feet. Clinical interpretability was evaluated by providing a quantification of the curvature variation in the medial-longitudinal and transverse arches and computing the Djiann-Annonier angle for normal and flat feet from these new ARS axes. To test the capability to also provide a sound description of the foot kinematics, the alignment between mean helical axes (MHA) and ARS axes was quantified., Results: ICC was 0.99 both inter- and intra-operator. Rotational consistency was 4.7 ± 3.5 ° and 6.2 ± 4.4° for the normal and flat feet, respectively; translational consistency was 4.4 ± 4.0 mm and 5.4 ± 2.9 mm for the normal and flat feet, respectively. In both these cases, the consistency was better than what was achieved by using principal axes of inertia. Curvature variation in the arches were well described and the measurements of the Djiann-Annoier angles from both normal and flat feet matched corresponding clinical observations. The angle between tibio-talar MHA and ARS mediolateral axis in the talus was 12.3 ± 6.0, while the angle between talo-calcaneal MHA and ARS anteroposterior axis in the calcaneus was 17.2 ± 5.6, suggesting good capability to represent joint kinematics., Conclusions: The proposed ARS definitions are robust and provide a solid base for the 3-dimensional description of posture and motion of the foot and ankle complex from medical imaging., (© 2021. The Author(s).)

Static and dynamic measurements of the medial longitudinal arch (MLA) in the foot are critical across different clinical and biomechanical research fields. While MLA deformation can be estimated using skin-markers for gait analysis, the current understanding of the correlates between skin-marker based models and radiographic measures of the MLA is limited. This study aimed at assessing the correlation and accuracy of skin-marker based measures of MLA deformation with respect to standard clinical X-ray based measures, used as reference. 20 asymptomatic subjects without morphological alterations of the foot volunteered in the study. A lateral X-ray of the right foot of each subject was taken in monopodalic upright posture with and without a metatarsophalangeal-joint dorsiflexing wedge. MLA angle was estimated in the two foot postures and during gait using 16 skin-marker based models, which were established according to the marker set of a validated multi-segment foot kinematic protocol. The error of each model in tracking MLA deformation was assessed and correlated with respect to standard radiographic measurements. Estimation of MLA deformation was highly affected by the skin-marker models. Skin-marker models using the marker on the navicular tuberosity as apex of the MLA angle showed the smallest errors (about 2 deg) and the largest correlations (R = 0.64-0.65; p < 0.05) with respect to the radiographic measurements. According to the outcome of this study, skin-marker based definitions of the MLA angle using the navicular tuberosity as apex of the arch may provide a more accurate estimation of MLA deformation with respect to that from radiographic measures., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: To systematically review and assess the methodological quality of guidelines for radiation protection in interventional radiology., Materials and Methods: On April 15 th , 2021, a systematic search for guidelines on radiation protection in interventional radiology was performed using MEDLINE, EMBASE, National Guideline Clearinghouse, and National Institute for Health and Clinical Excellence databases. Among retrieved guidelines, we then excluded those not primarily focused on radiation protection or on interventional radiology. Authors' professional role and year of publication were recorded for each included guideline. Guideline quality evaluation was performed independently by three authors using the six-domain tool "AGREE II", with an overall guideline quality score divided into three classes: low (<60%), acceptable (60-80%), and good quality (>80%)., Results: Our literature search identified 106 citations: after applying exclusion criteria, 11 guidelines published between 2009 and 2018 were included, most of their authors being interventional radiologists (168/224, 75%). Overall quality of included guidelines was acceptable (median 72%, interquartile range 64-83%), with only one guideline (9%) with overall low quality and four guidelines (36%) with overall good quality. Among AGREE II domains, "Scope and Purpose", "Clarity of Presentations", and "Editorial Independence" had the best results (87%, 76%, and 75% respectively), while "Applicability", "Rigor of Development", and "Stakeholder Involvement" the worst (46%, 49%, and 52% respectively)., Conclusion: Considering all guidelines, the overall methodological quality was acceptable with one third of them reaching the highest score class. The "Applicability" domain had the lowest median score, highlighting a practical implementation gap to be addressed by future guidelines., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Based on literature, intensity-modulated radiation therapy (IMRT) provides less related toxicity compared with conventional 2D/3D-RT with no impact on oncological outcomes for oropharyngeal cancer. The aim of this systematic review and meta-analysis is to assess whether IMRT might provide similar clinical outcomes with reduced related toxicity in comparison with conventional 2D/3D RT in patients treated for clinically advanced oropharyngeal cancer (OPC). Inclusion criteria for paper selection included: squamous OPC patients, treatment performed by concomitant CRT or RT alone, four treatment performed for curative intent, and presence of clinical outcome of interest, namely, overall survival (OS) and disease-free survival (DFS) and full paper available in English. Acute and late toxicities were retrieved together with OS and DFS. Crude relative risk estimates of relapse and death comparing 2D/3D-RT versus IMRT were calculated from tabular data, extracting events at 2-3 years of follow-up. Eight studies were selected. Six of them were included in the meta-analysis considering summary relative risk. Considering both acute and late toxicities, the considered studies evidenced advantages for IMRT populations, with the 2D/3D-RT population showing higher frequencies than the IMRT one. No statistical difference between IMRT and 2D/3D-RT in terms of death (SRR = 0.93, 95% CI: 0.83-1.04 with no heterogeneity I 2  = 0%) and relapse (SRR = 0.92, 95% CI: 0.83-1.03, with no heterogeneity I 2  = 0%) was found. Results of our study suggest the improvement in the therapeutic index with IMRT with evidenced reduced toxicity without any worsening in clinical outcome when compared to 2D/3DCRT., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Acquired adult flatfoot is a frequent deformity which implies multiple, complex and combined 3D modifications of the foot skeletal structure. The difficult thorough evaluation of the degree of severity pre-op and the corresponding assessment post-op can now be overcome by cone-beam (CBCT) technology, which can provide access to the 3D skeletal structure in weight-bearing. This study aims to report flatfoot deformities originally in 3D and in weight-bearing, with measurements taken using two different bone segmentation techniques. 21 such patients, with indication for surgical corrections, underwent CBCT (Carestream, US) while standing on one leg. From these scans, 3D models of each bone of the foot were reconstructed by using two different state-of-the-art segmentation tools: a semi-automatic (Mimics Innovation Suite, Materialise, Belgium), and an automatic (Bonelogic Ortho Foot and Ankle, Disior, Finland). From both reconstructed models, Principal Component Analysis was used to define anatomical reference frames, and original foot and ankle angles and other parameters were calculated mostly based on the longitudinal axis of the bones, in anatomical plane projections and in 3D. Both bone model reconstructions revealed a considerable valgus of the calcareous, plantarflexion and internal rotation of the talus, and typical Meary's angles in the lateral and transverse plane projections. The mean difference from these angles between semi-automatic and automatic segmentations was larger than 3.5 degrees for only 3 of the 32 measurements, and a large number of these differences were not statistically significant. CBCT and the present techniques for bone shape reconstruction finally provide a novel and valuable 3D assessment of complex foot deformities in weight-bearing, eliminating previous limitations associated to unloaded feet and bidimensional measures. Corresponding measurements on the bone models from the two segmentation tools compared well. Other more representative measurements can be defined in the future using CBCT and these techniques., (© 2021. The Author(s).)

The aim of this study was to analyze the extent to which postoperative patellofemoral joint (PFJ) kinematics assessed at 6-month follow-up after total knee arthroplasty (TKA) mimics the intraoperative kinematics after final component implantation. The study hypothesis, already proved in terms of tibiofemoral joint (TFJ) kinematics, is that the intraoperative assessment of PFJ kinematics after component implantation is also capable of predicting postoperative knee kinematics during activities of daily living. Twenty patients selected for TKA with patellar resurfacing were implanted using surgical navigation, including patellar component positioning via a novel computer-assisted procedure. This allowed for intraoperative TFJ and PFJ kinematic assessment after final component implantation. At 6-month follow-up, all patients were contacted for follow-up control; in addition to clinical examination, this implied postoperative kinematics assessments by three-dimensional video fluoroscopy of the replaced knee during standard activities of daily living. Several traditional PFJ, as well as TFJ, rotations and translations were calculated intra- and postoperatively and then statistically compared. Good postoperative replication of the intraoperative measurements was observed for most of PFJ variables analyzed, as well as those for TFJ. Relevant statistical analysis also supported the significant consistency between the intra- and postoperative measurements. Pertaining to the present findings on a statistical basis, intraoperative measurements performed at both TFJ and PFJ kinematics using a surgical navigation system under passive conditions, are predictive of the overall knee kinematics experienced at postoperative follow-ups by the same replaced knees in typical activities of daily living., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: To compare weight-bearing cone-beam computer tomography (CBCT) and conventional computer tomography (CT)-based measurements of patellofemoral alignment and stability in patients surgically treated for recurrent patellar dislocation. These scans implied respectively single-leg up-right posture, the knee flexed, and lower limb muscles activation, versus supine position with the knee extended., Methods: A total of 17 patients (11 males/6 females) after surgical reconstruction with fascia lata allograft for recurrent patellofemoral dislocation were analyzed at 60-month follow-up. Tilt and congruence angles and tibial tuberosity-trochlear groove (TT-TG) offset were measured on images obtained from CBCT and conventional CT scans by three independent and expert radiologists. Paired t tests were performed to compare measurements obtained from the two scans. Inter-rater reliability was assessed using a two-way mixed-effects model intra-class correlation coefficient (ICC)., Results: Only TT-TG offset was found significantly smaller (p < 0.001) in CBCT (mean 9.9 ± 5.3 mm) than in conventional CT (mean 15.9 ± 4.9 mm) scans. ICC for tilt and congruence angles and for TT-TG offset ranged between 0.80-0.94 with measurements in CBCT scans, between 0.52 and0.78 in conventional CT., Conclusion: In patients surgically treated for recurrent patellar dislocation, TT-TG offset was found overestimated with conventional CT. All measurements of patellofemoral stability and alignment were found more consistent when obtained with weight-bearing CBCT compared to conventional CT.

It is established that human movements in the vicinity of a permanent static magnetic field, such as those in magnetic resonance imaging (MRI) scanners induce electric fields in the human body; this raises potential severe risks of health to radiographers and cleaners exposed routinely to these fields in MRI rooms. The relevant directives and parameters, however, are based on theoretical models, and accurate studies on the simulation of the effects based on human movement data obtained in real conditions are still lacking. Two radiographers and one cleaner, familiar with MRI room activities and these directives, were gait analyzed during the execution of routine job motor tasks at different velocities. Full body motion was recorded in a gait laboratory arranged to reproduce the workspace of a room with an MRI full-body scanner. Body segments were tracked with clusters of at least three markers, from which position and velocity of the centroids were calculated. These were used as input in an established computer physical model able to map the stray field in an MRI room. The spatial peak values of the calculated electric field induced by motion of the head and of the entire body during these tasks, for both the health and sensory effects, were found smaller than the thresholds recommended by the European directives, for both 1.5 T and 3.0 T MRI. These tasks therefore seem to guarantee the safety of MRI room operators according to current professional good practice for exposure risks. Physical modeling and experimental measures of human motion can also support occupational medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gurrera, Leardini, Ortolani, Durante, Caputo, Gallias, Abbate, Rinaldi, Iacoviello, Acri, Vermiglio and Marrale.)

Introduction: Our aim was to investigate the means radiographers and radiographers in training (RTrs) use to seek information on magnetic resonance imaging (MRI) physics and technical issues., Methods: An estimated 3000 radiographers and RTrs were reached by e-mail. We proposed an online survey with eight English-language multiple choice questions investigating how often radiographers have doubts about MRI physics or technical issues, where and what kind of information they search for, and on which websites. The statistical χ 2 test was used., Results: We obtained 300 answers from European professionals (228 radiographers, 72 RTrs) from 9 European countries, with 288 of 300 (96%) responses coming from Italy. Within the Italian respondents, 41% of RTrs have doubts about MRI physics versus 56% of radiographers (p = 0.028). Basic MRI sequences details are more searched by RTrs (36%) than radiographers (22%) (p = 0.088), as well as clinical protocols (64% versus 44%, p = 0.054). Radiographers and RTrs mostly search on the Internet (74% versus 81%, p = 0.404); "older colleagues" are more frequently asked for information by RTrs (27% versus 61%, p = 0.001), they consult the "MRI manufacturer" less frequently (11% versus 34%, p = 0.001); and 66% of radiographers and 72% of RTrs search "in mother-language and English" (p = 0.590). For clinical protocols RTrs prefer the website mriquestions.com (17% versus 44%, p = 0.001). Websites most used were: mriquestions.com (41%), radiopaedia.org (31%), and mrimaster.com (13%). In addition, 30 respondents mentioned using the Italian site fermononrespiri.com., Conclusion: Italian radiographers and RTrs frequently search for information about MRI physics and technical issues, with slight differences between groups regarding sources and clinical protocols. Protocol setting, and MRI physics and sequences seem to be the main limitations of RTr knowledge. To remedy this gap, more time on training/university lectures and a rethinking of the practical training activities is required., (Copyright © 2020. Published by Elsevier Inc.)

Background: For the diagnosis and treatment of foot and ankle disorders, objective quantification of the absolute and relative orientation angles is necessary. The present work aims at assessing novel techniques for 3D measures of foot bone angles from current Cone-Beam technology., Methods: A normal foot was scanned via weight-bearing CT and 3D-model of each bone was obtained. Principal Component Analysis, landmark-based and mid-diaphyseal axes were exploited to obtain bone anatomical references. Absolute and relative angles between calcaneus and first metatarsal bone were calculated both in 3D and in a simulated sagittal projections. The effects of malpositioning were also investigated via rotations of the entire foot model., Results: Large angle variations were found between the different definitions. For the 3D relative orientation, variations larger than 10 degrees were found. Foot malposition in axial rotation or in varus/valgus can result in errors larger than 5 and 3 degrees, respectively., Conclusions: New measures of foot bone orientation are possible in 3D and in weight-bearing, removing operator variability and the effects of foot positioning., (Copyright © 2020 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.)

Aim: To provide a literature review on risk factors and strategies to prevent acute carotid blowout (CBO) syndrome in patients who underwent reirradiation (reRT) for recurrent head and neck (HN) malignancies., Patients and Methods: Inclusion criteria were: 1) CBO following reRT in the HN region, 2) description on patient-, tumor- or treatment-related risk factors, 3) clinical or radiological signs of threatened or impending CBO, and 4) CBO prevention strategies., Results: Thirty-five studies were selected for the analysis from five hundred seventy-seven records. Results provided indications on clinical, radiological and dosimetric parameters possibly associated with higher risk of CBO. Endovascular procedures (artery occlusion and stenting) to prevent acute massive hemorrhage in high risk patients were discussed., Conclusion: Literature data are still scarce with a low level of evidence. Nevertheless, the present work provides a comprehensive review useful for clinicians as a multidisciplinary pragmatic tool in their clinical practice., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Measurements of plantar loading reveal foot-to-floor interaction during activity, but information on bone architecture cannot be derived. Recently, cone-beam computer tomography (CBCT) has given visual access to skeletal structures in weight-bearing. The combination of the two measures has the potential to improve clinical understanding and prevention of diabetic foot ulcers. This study explores the correlations between static 3D bone alignment and dynamic plantar loading., Methods: Sixteen patients with diabetes were enrolled (group ALL): 15 type 1 with (N, 7) and without (D, 8) diabetic neuropathy, and 1 with latent autoimmune diabetes. CBCT foot scans were taken in single-leg upright posture. 3D bone models were obtained by image segmentation and aligned in a foot anatomical reference frame. Absolute inclination and relative orientation angles and heights of the bones were calculated. Pressure patterns were also acquired during barefoot level walking at self-selected speed, from which regional peak pressure and absolute and normalised pressure-time integral were worked out at hallux and at first, central and fifth metatarsals (LOAD variables) as averaged over five trials. Correlations with 3D alignments were searched also with arch index, contact time, age, BMI, years of disease and a neuropathy-related variable., Results: Lateral and 3D angles showed the highest percentage of significant (p < 0.05) correlations with LOAD. These were weak-to-moderate in the ALL group, moderate-to-strong in N and D. LOAD under the central metatarsals showed moderate-to-strong correlation with plantarflexion of the 2nd and 3rd phalanxes in ALL and N. LOAD at the hallux increased with plantarflexion at the 3rd phalanx in ALL, at 1st phalanx in N and at 5th phalanx in D. Arch index correlated with 1st phalanx plantarflexion in ALL and D; contact time showed strong correlation with 2nd and 3rd metatarsals and with 4th phalanx dorsiflexion in D., Conclusion: These preliminary original measures reveal that alteration of plantar dynamic loading patterns can be accounted for peculiar structural changes of foot bones. Load under the central metatarsal heads were correlated more with inclination of the corresponding phalanxes than metatarsals. Further analyses shall detect to which extent variables play a role in the many group-specific correlations.

Introduction: Dignity Therapy (DT) is a brief, individualized, narrative psychotherapy developed to reduce psychosocial and existential distress, and promote dignity, meaning, and hope in end of life patients. Previous studies have shown that DT was effective in reducing anxiety and depression, and improving dignity-related distress. However, less is known about its efficacy on spiritual well-being. The aim of this study is to contribute to the existing literature by investigating the effects of DT on specific dimensions of spiritual well-being, demoralization and dignity-related distress in a sample of terminally ill patients. Methods: A randomized, controlled trial was conducted with 64 terminally ill patients who were randomly assigned to the intervention group (DT + standard palliative care) or the control group (standard palliative care alone). The primary outcome measures were Meaning, Peace, and Faith whereas the secondary outcome measures were (loss of) Meaning and purpose, Distress and coping ability, Existential distress, Psychological distress, and Physical distress. All measures were assessed at baseline (before the intervention), 7-10 and 15-20 days after the baseline assessment. The trial was registered with ClinicalTrials.gov (Protocol Record NCT04256239). Results: The MANOVA yielded a significant effect for the Group X Time interaction. ANOVA with repeated measures showed a significant effect of time on peace and a significant Group X Time interaction effect on peace. Post hoc comparisons revealed that, while there was a decrease in peace from pre-treatment to follow-up and from post-treatment to follow-up in the control group, there was no such trend in the intervention group. Discussion: This study provides initial evidence that patients in the DT intervention maintained similar levels of peace from pre-test to follow-up, whereas patients in the control group showed a decrease in peace during the same time period. We did not find significant longitudinal changes in measures of meaning, faith, loss of meaning and purpose, distress and coping ability, existential, psychological and physical distress. The findings of our study are of relevance in palliative care and suggest the potential clinical utility of DT, since they offer evidence for the importance of this intervention in maintaining peace of mind for terminally ill patients., (Copyright © 2020 Iani, De Vincenzo, Maruelli, Chochinov, Ragghianti, Durante and Lombardo.)

Background: Angiogenesis plays an important role in head and neck squamous cell carcinoma (HNSCC) progression. This pilot study was designed to compare the distribution of 68 Ga-NODAGA-RGD PET/CT for imaging α v β 3 integrins involved in tumor angiogenesis to 18 F-FDG PET/CT in patients with HNSCC., Material and Methods: Ten patients (aged 58.4 ± 8.3 years [range, 44-73 years], 6 males, 4 females) with a total of 11 HNSCC were prospectively enrolled. Activity mapping and standard uptake values (SUV) from both 68 Ga-NODAGA-RGD and 18 F-FDG PET/CT scans were recorded for primary tumor and compared with the Wilcoxon signed-rank test. The relation between the SUV of both tracers was assessed using the Spearman correlation., Results: All HNSCC tumors were visible with both tracers. Quantitative analysis showed higher 18 F-FDG SUV max in comparison to 68 Ga-NODAGA-RGD (14.0 ± 6.1 versus 3.9 ± 1.1 g/mL, p = 0.0017) and SUV mean (8.2 ± 3.1 versus 2.0 ± 0.8 g/mL, p = 0.0017). Both 18 F-FDG and 68 Ga-NODAGA-RGD uptakes were neither correlated with grade, HPV status nor p16 protein expression (p ≥ 0.17)., Conclusion: All HNSCC tumors were detected with both tracers with higher uptake with 18 F-FDG, however. 68 Ga-NODAGA-RGD has a different spatial distribution than 18 F-FDG bringing different tumor information., Trial Registration: NCT, NCT02666547. Registered 12.8.2012.

Musculoskeletal radiology has been mostly limited by the option between imaging under load but in two dimensions (i.e., radiographs) and three-dimensional (3D) scans but in unloaded conditions (i.e., computed tomography [CT] and magnetic resonance imaging in a supine position). Cone-beam technology is now also a way to image the extremities with 3D and weight-bearing CT. This article discusses the initial experience over a few studies in progress at an orthopaedic center. The custom design of total ankle replacements, the patellofemoral alignment after medial ligament reconstruction, the overall architecture of the foot bones in the diabetic foot, and the radiographic assessment of the rearfoot after subtalar fusion for correction of severe flat foot have all taken advantage of the 3D and weight-bearing feature of relevant CT scans. To further support these novel assessments, techniques have been developed to obtain 3D models of the bones from the scans and to merge these with state-of-the-art gait analyses., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Purpose: To evaluate toxicity and clinical outcomes in patients with eyelid tumour treated with contact high-dose-rate brachytherapy (HDR-BT)., Material and Methods: Between April 2010 and August 2017, 10 consecutive patients with tumour of the eyelid underwent contact HDR-BT and custom-made surface mould. Every applicator was manually built using conventional thermoplastic material and standard plastic catheters. The median dose prescribed was 42 Gy (range, 30-48) with a median dose per fraction of 3.5 Gy (range, 2-4.5). The dose was delivered in a median of 12 fractions (range, 10-17) over a median of 16 days. In all cases, an ocular shield was placed to reduce the dose to the eye. Acute and late toxicity was evaluated according to RTOG toxicity criteria., Results: We analyzed data of 9 of 10 patients (one patient was excluded because he did not give consent for investigation). The median age was 68 years (range, 31-88). According to the TNM-UICC staging system, 4, 1 and 4 patients were stage IA, IB and IC, respectively. Basal cell and sebaceous gland carcinomas were reported in 5 and 2 patients, respectively; other histological types were non-Hodgkin lymphoma and plasmacytoma. After a median follow-up of 51 months (range, 16-90), there was no evidence of local or distant recurrence. The treatment was very well tolerated. Most commonly acute reactions consisted of low grade (G1-G2) conjunctivitis and skin erythema. Only one patient required a temporary interruption of the treatment due to acute G2 conjunctivitis and G3 lid erythema. Only one G2 late toxicity was reported (corneal ulceration), without resulting in functional impairment or blindness., Conclusions: Our results suggest that contact HDR-BT with a customized applicator is safe, effective and offers very good local control and can be considered for the treatment of eyelid tumours., Competing Interests: The authors report no conflict of interest., (Copyright: © 2019 Termedia Sp. z o. o.)

The protozoan parasite Bonamia ostreae has been associated with the decline of flat oyster Ostrea edulis populations in some European countries. Control of shellfish diseases mostly relies on prevention measures including transfer restrictions and stock management measures such as breeding programmes. These prevention and mitigation measures require a better understanding of interactions between host and pathogens. Previous in vitro studies allowed identifying apoptosis as a mechanism activated by the flat oyster in response to B. ostreae. However, these experiments also suggested that the parasite is able to regulate apoptosis in order to survive and multiply within hemocytes. By simplifying the conditions of infection, in vitro studies allow identifying most distinct features of the response of the host. In order to appreciate the relative importance of apoptosis in this response at the oyster scale, in vivo trials were carried out by injecting with parasites oysters from two French locations, Quiberon Bay (Brittany) and Diana Lagoon (Corsica). Apoptosis was investigated on pools of hemolymph from oysters collected at early and later times after injection using previously developed tools. Apoptotic cellular activities including intracytoplasmic calcium concentration, mitochondrial membrane potential and phosphatidyl serine externalization were analysed using flow cytometry. Moreover, the expression of flat oyster genes involved in both extrinsic and intrinsic pathways was measured using real time quantitative PCR., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Accurate geometrical models of bones and cartilage are necessary in biomechanical modelling of human joints, and in planning and designing of joint replacements. Image-based subject-specific model development requires image segmentation, spatial filtering and 3-dimensional rendering. This is usually based on computed tomography (CT) for bone models, on magnetic resonance imaging (MRI) for cartilage models. This process has been reported extensively in the past, but no studies have ever compared the accuracy and quality of these models when obtained also by merging different imaging modalities. The scope of the present work is to provide this comparative analysis in order to identify optimal imaging modality and registration techniques for producing 3-dimensional bone and cartilage models of the ankle joint., Methods: One cadaveric leg was instrumented with multimodal markers and scanned using five different imaging modalities: a standard, a dual-energy and a cone-beam CT (CBCT) device, and a 1.5 and 3.0 Tesla MRI devices. Bone, cartilage, and combined bone and cartilage models were produced from each of these imaging modalities, and registered in space according to matching model surfaces or to corresponding marker centres. To assess the quality in overall model reconstruction, distance map analyses were performed and the difference between model surfaces obtained from the different imaging modalities and registration techniques was measured., Results: The registration between models worked better with model surface matching than corresponding marker positions, particularly with MRI. The best bone models were obtained with the CBCT. Models with cartilage were defined better with the 3.0 Tesla than the 1.5 Tesla. For the combined bone and cartilage models, the colour maps and the numerical results from distance map analysis (DMA) showed that the smallest distances and the largest homogeneity were obtained from the CBCT and the 3.0 T MRI via model surface registration., Conclusions: These observations are important in producing accurate bone and cartilage models from medical imaging and relevant for applications such as designing of custom-made ankle replacements or, more in general, of implants for total as well as focal joint replacements., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Many failures in total joint replacement are associated to prosthesis-to-bone mismatch. With recent additive-manufacturing, that is, 3D-printing, custom-made prosthesis can be created by laser-melting metal powders layer-by-layer. Ankle replacement is particularly suitable for this progress because of the limited number of sizes and the poor bone stock. In this study a novel procedure is presented for subject-specific ankle replacements, including medical-imaging, joint modelling, prosthesis design, and 3D-printing. Three shank-foot specimens were CT-scanned, and corresponding 3D bone models of the tibia, fibula, talus, and calcaneus were obtained. From these models, specimen-specific implant sets were designed according to three different concepts, and 3D-printed from cobalt-chromium-molybdenum powder. Accuracy of the overall procedure was assessed via distance map comparisons between original anatomical and final metal implants. Restoration of natural ankle joint mechanics was check after implantation of each of the three sets. In a special rig, a manually-driven dorsi/plantar-flexion was applied throughout the passive arc. Additionally, at three different joint positions, joint torques were imposed in the frontal and axial anatomical planes. Mean manufacturing errors were found to be smaller than 0.08 mm. Consistent motion patterns were observed over repetitions, with the mean standard deviation smaller than 1.0 degree. In each ankle specimen, mobility, and stability at the replaced joints compared well with the original natural condition. For the first time, custom-made implants for total ankle replacements were designed, manufactured with additive technology and tested. This procedure is a first fundamental step toward the development of completely personalized prostheses. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res., (© 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Musculo-skeletal modelling, 3D printing of bone models and also custom design of relevant prostheses starts from accurate STL files. These are obtained from medical imaging after careful segmentation and 3D reconstruction using specialized software, but most of these are very expensive. The aim of the present study is to assess and compare alternative software available for free. Three freeware software were selected from the most popular, and one standard platform was made available at the institute of the authors. Using each of these four software and starting from available DICOM files obtained previously by a CT scanner, three different bone models were reconstructed from each of five different human anatomical areas for a total of 60 bone model reconstructions. A young radiographer performed the bone reconstruction without specific technical training. 3D spatial matching of corresponding anatomical models was also performed to determine distance-maps for the assessment of final surface quality. In all four software many valuable features were available, with minimum differences, and bone models of good quality were obtained. Large differences in file sizes (mean range over the five anatomical models 66-338) and in the number of triangles (870-1350 thousands) were found, with triangles for MByte ratio ranging from about 4 to 20 thousands. The distance-map analysis revealed that root mean square deviation averaged over the five anatomical models ranged from 0.13 to 2.21 mm for the six spatial matches between the four software. These software are suitable for 3D bone model reconstruction, and do not require special training, and as such these can open up opportunities for biomechanical modelling and medical education., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the treatment-induced toxicity (as primary endpoint) and the efficacy (as secondary endpoint) of stereotactic body radiation therapy (SBRT) in the treatment of mediastinal lymph nodes (LNs) in the so-called no-fly zone (NFZ) in cancers with various histology., Material and Methods: Forty-two patients were retrospectively analyzed. Institutional dose/volume constraints for organs at risk (OARs) derived by published data were strictly respected. The correlation between treatment-related variables and toxicity was investigated by logistic regression, Chi-squared test or Fisher's exact test. Overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS) and local control (LC) were collected from the follow-up reports. The impact of potential predictive factors on LC, PFS and OS were estimated by Cox proportional-hazard regression., Results: Median follow-up time was 16 months (range 1-41). Four patients had esophageal G1 toxicity. Ten and six patients had G1 and G2 pulmonary toxicity, respectively. Treatment site and irradiation technique were significantly correlated with G ≥ 2 and G ≥ 1 toxicity, respectively. OS probability at 19 months was 88.3% and corresponded to CSS. LC probability at 16 months was 66.3% (median LC duration: 22 months, range 1-41). Fifteen patients (35.7%) were disease-free at 25 months (median time, range 1-41). The biologically effective dose (BED) and the target dose coverage indexes were significantly correlated with LC., Conclusions: SBRT can be considered as a safe treatment option for selected patients with oligo-metastases/recurrences in the NFZ, if strict dose/volume constraints are applied.

Kinematics and flexibility properties of both natural and replaced ankle joints are affected by the geometry of the articulating surfaces. Recent studies proposed an original saddle-shaped, skewed, truncated cone with laterally oriented apex, as tibiotalar contact surfaces for ankle prosthesis. The goal of this study was to compare in vitro this novel design with traditional cylindrical or medially centered conic geometries in terms of their ability to replicate the natural ankle joint mechanics. Ten lower limb cadaver specimens underwent a validated process of custom design for the replacement of the natural ankle joint. The process included medical imaging, 3D modeling and printing of implantable sets of artificial articular surfaces based on these three geometries. Kinematics and flexibility of the overall ankle complex, along with the separate ankle and subtalar joints, were measured under cyclic loading. In the neutral and in maximum plantarflexion positions, the range of motion under torques in the three anatomical planes of the three custom artificial surfaces was not significantly different from that of the natural surfaces. In maximum dorsiflexion the difference was significant for all three artificial surfaces at the ankle complex, and only for the cylindrical and medially centered conic geometries at the tibiotalar joint. Natural joint flexibility was restored by the artificial surfaces nearly in all positions. The present study provides experimental support for designing articular surfaces matching the specific morphology of the ankle to be replace, and lays the foundations of the overall process for designing and manufacturing patient-specific total ankle replacements., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Despite the genomic characterization of pancreatic cancer (PC), marked advances in the development of prognosis classification and novel therapeutic strategies have yet to come. The present study aimed to better understand the genomic alterations associated with the invasive phenotype of PC, in order to improve patient selection for treatment options. A total of 30 PC samples were analysed by either whole transcriptome (9 samples) or exome sequencing (21 samples) on an Illumina platform (75X2 or 100X2 bp), and the results were matched with normal DNA to identify somatic events. Single nucleotide variants and insertions and deletions were annotated using public databases, and the pathogenicity of the identified variants was defined according to prior knowledge and mutation-prediction tools. A total of 43 recurrently altered genes were identified, which were involved in numerous pathways, including chromatin remodelling and DNA damage repair. In addition, an analysis limited to a subgroup of early stage patients (50% of samples) demonstrated that poor prognosis was significantly associated with a higher number of known PC mutations (P=0.047). Samples from patients with a better overall survival (>25 months) harboured an average of 24 events, whereas samples from patients with an overall survival of <25 months presented an average of 40 mutations. These findings indicated that a complex genetic profile in the early stage of disease may be associated with increased aggressiveness, thus suggesting an urgent requirement for an innovative approach to classify this disease.