Single-Shot Diagnosis of Electron Energy Evolution via Streaked Betatron X Rays in a Curved Laser Wakefield Accelerator.

We report on an experimental observation of the streaking of betatron x rays in a curved laser wakefield accelerator. The streaking of the betatron x rays was realized by launching a laser pulse into a plasma with a transverse density gradient. By controlling the plasma density and the density gradient, we realized the steering of the laser driver, electron beam, and betatron x rays simultaneously. Moreover, we observed an energy-angle correlation of the streaked betatron x rays and utilized it in diagnosing the electron acceleration process in a single-shot mode. Our work could also find applications in advanced control of laser beam and particle propagation. More importantly, the angular streaked betatron x ray has an intrinsic spatiotemporal correlation, which makes it a promising tool for single-shot pump-probe applications.

Quality of life gains in frail and intermediate-fit patients with multiple Myeloma: Findings from the prospective HOVON123 clinical trial.

BACKGROUND: Frailty in newly-diagnosed multiple myeloma (NDMM) patients is associated with treatment-related toxicity, which negatively affects health-related quality of life (HRQoL). Currently, data on changes in HRQoL of frail and intermediate-fit MM patients during active treatment and post-treatment follow-up are absent. METHODS: The HOVON123 study (NTR4244) was a phase II trial in which NDMM patients ≥ 75 years were treated with nine dose-adjusted cycles of Melphalan-Prednisone-Bortezomib (MPV). Two HRQoL instruments (EORTC QLQ-C30 and -MY20) were obtained before start of treatment, after 3 and 9 months of treatment and 6 and 12 months after treatment for patients who did not yet start second-line treatment. HRQoL changes and/or differences in frail and intermediate-fit patients (IMWG frailty score) were reported only when both statistically significant (p < 0.005) and clinically relevant (>MID). RESULTS: 137 frail and 71 intermediate-fit patients were included in the analysis. Compliance was high and comparable in both groups. At baseline, frail patients reported lower global health status, lower physical functioning scores and more fatigue and pain compared to intermediate-fit patients. Both groups improved in global health status and future perspective; polyneuropathy complaints worsened over time. Frail patients improved over time in physical functioning, fatigue and pain. Improvement in global health status occurred earlier than in intermediate-fit patients. CONCLUSION: HRQoL improved during anti-myeloma treatment in both intermediate-fit and frail MM patients. In frail patients, improvement occurred faster and, in more domains, which was retained during follow-up. This implies that physicians should not withhold safe and effective therapies from frail patients in fear of HRQoL deterioration.

Research Note: Water applied direct-fed microbial reduced mortality in heat stressed broilers.

Pressure to reduce the use of antibiotics in the poultry industry has intensified research on alternative solutions to support intestinal health, including but not limited to direct fed microbials (DFM). Heat stress is known to impact intestinal health and function. The aim of this study was to determine efficacy of a water applied DFM product on broiler performance during the summer period. One of two treatments were randomly allocated to 12 replicate floor pens each: a control treatment and a treatment provided daily with a dual strain DFM comprised of Lactobacillus acidophilus AG01 and Bifidobacterium animalis AG02 at 1 × 108 CFU/bird/d. Each pen contained 20 Ross 308 broilers. All birds were fed the same three-phased wheat- and soybean meal-based diets. Body weight, feed intake, feed conversion ratio, and mortality were measured at d 0, 10, 24, 35, and 42. Due to natural extreme external temperature conditions, all birds were subject to heat stress during the end of the grower phase up to and including the finisher phase. Temperature was on average 5°C higher compared to industry recommendation. No significant differences were found in growth performance between the control and DFM treatment, yet BW at d 42 in both treatments was reduced by 19% compared to the breed standard. The DFM treatment significantly reduced mortality among the birds. Overall mortality from d 1 to d 35 was reduced from 4.58% to 0.42% (P = 0.023) and overall mortality from d 1 to d 42 was reduced from 5.83 to 0.83% (P = 0.027). This was driven by the difference in heat-stress related mortality in the finisher phase from d 25 to d 42, where mortality reached only 0.44% in the DFM treatment versus 2.88% in the unsupplemented control treatment. Post-mortem analysis confirmed heat-stress related hypoxia. In conclusion, the dual strain DFM may have provided improved (intestinal) homeostasis and barrier function allowing increased resilience to heat stress in broilers.

Elucidating the Varying Impact of Necrotic Enteritis Using Performance and Health Indicators in Broiler Infection Models.

Necrotic enteritis (NE) continues to be a significant burden to the poultry industry, compounded by pressure to reduce antibiotic use. Researchers use NE-challenge models to study the infection biology of NE and as screening tools to develop potential novel interventions. Currently, data are limited comparing such models between research establishments, and few indicate which quantitative metrics provide the most accurate measure for determining the efficacy of interventions. We compared data from 10 independent NE-challenge trials incorporating six challenge models employed in four geographical regions to determine the extent of variability in bird responses and to determine, using principal component analysis (PCA), which variables discriminated most effectively between nonchallenged control (NC) and challenged control (CC) groups. Response variables related to growth performance (weight gain, feed intake, feed conversion), health (mortality, lesion scores, NE induction rate), and, in three trials only, gut integrity (tight junction protein claudin-1, claudin-2, and zonula occludens-1 expression, coccidia counts, and intestinal permeability [assessed by FITC-dextran assay]). Treatments included a CC, which varied between trials (for example, in Eimeria predisposition, Clostridium perfringens strain, and days of inoculation), and a NC. The degree of response to challenge in CC birds varied significantly among models and trials. In all trials, lesion scores 1 to 4 days postchallenge were increased in CC vs. NC birds and varied both within and among models (by 0.29-1.17 points and 0.05-2.50 points, respectively). In addition, NE-related mortality at day 28 was increased in CC vs. NC, both within and among models (by 1.79%-4.72% and 0.02%-16.70%, respectively), and final (day 35 or 42) body weight was reduced by 3.9%-14.4% and overall FCR increased by up to 27% across trials (P , 0.05). A PCA on the combined dataset including only performance indicators failed to adequately differentiate NC and CC groups. However, the combination of performance and gut integrity variables and standardization of data by trial and phase achieved greater resolution between groups. This indicated that the inclusion of both types of variables in future NE-challenge studies would enable the generation of more robust predictions about intervention efficacy from different types of infection models. A final PCA based on a subset of key indicator variables, including body weight, feed intake, feed conversion ratio, mortality, and lesion score, achieved a good level of separation between NC and CC status of birds and could, with further research, be a useful supplement to existing approaches for assessing and predicting the NE status of birds in the field.

Determinación del impacto variable de la enteritis necrótica mediante indicadores de rendimiento y salud en modelos de infección de pollos de engorde. La enteritis necrótica (EN) sigue siendo un problema importante para la industria avícola, que se ha agudizado por la presión para reducir el uso de antibióticos. Los investigadores utilizan modelos de desafío de enteritis necrótica para estudiar la biología de la infección de este problema y como herramientas de detección para desarrollar posibles intervenciones novedosas. Actualmente, los datos que comparan dichos modelos entre grupos de investigación son limitados y pocos indican qué métricas cuantitativas proporcionan la medida más precisa para determinar la eficacia de las intervenciones. Comparamos datos de 10 ensayos independientes de desafío para enteritis necrótica que incorporan seis modelos de desafío empleados en cuatro regiones geográficas para determinar el grado de variabilidad en las respuestas de las aves y determinar, utilizando el análisis de componentes principales (PCA), qué variables discriminaron más efectivamente entre el control no desafiado (NC) y grupos de control desafiados (CC). Variables de respuesta relacionadas con el rendimiento del crecimiento (aumento de peso, consumo de alimento, conversión alimenticia), salud (mortalidad, puntuaciones de lesiones, tasa de inducción de enteritis necrótica) y, en sólo tres ensayos, la integridad intestinal (proteína de unión estrecha claudina-1, claudina-2, y expresión de zonula occludens-1, recuentos de coccidias y permeabilidad intestinal [evaluada mediante ensayo FITC-dextrano]). Los tratamientos incluyeron un control desafiado, que fue variable entre los ensayos (por ejemplo, en la predisposición a Eimeria, la cepa de Clostridium perfringens y los días de inoculación) y un control no desafiado. El grado de respuesta al desafío en aves del grupo control desafiado varió significativamente entre modelos y ensayos. En todos los ensayos, las puntuaciones de lesiones de 1 a 4 días después del desafío aumentaron en las aves del grupo control desafiado en comparación con el control no desafiado y variaron tanto dentro como entre los modelos (entre 0.29 y 1.17 puntos y entre 0.05 y 2.50 puntos, respectivamente). Además, la mortalidad relacionada con enteritis necrótica en el día 28 aumentó en el control desafiado en comparación con el control no desafiado, tanto dentro como entre modelos (entre un 1.79% y un 4.72% y entre un 0.02% y un 16.70%, respectivamente), y el peso corporal final (día 35 o 42). se redujo entre un 3.9% y un 14.4% y la conversión alimenticia en general aumentó hasta un 27% en todos los ensayos (P ,0.05). El análisis de componentes principales sobre el conjunto de datos combinado que incluye solo indicadores de desempeño no logró diferenciar adecuadamente los grupos control no desafiado y desafiado. Sin embargo, la combinación de variables de rendimiento e integridad intestinal y la estandarización de los datos por ensayo y fase lograron una mayor resolución entre los grupos. Esto indicó que la inclusión de ambos tipos de variables en futuros estudios de desafío para enteritis necrótica permitiría la generación de predicciones más sólidas sobre la eficacia de la intervención a partir de diferentes tipos de modelos de infección. Un análisis de componentes principales final basado en un subconjunto de variables indicadoras clave, incluido el peso corporal, el consumo de alimento, el índice de conversión alimenticia, la mortalidad y la puntuación de las lesiones, logró un buen nivel de separación entre el estado de las aves no desafiadas y desafiadas y podría, con más investigación, ser un complemento útil a los enfoques existentes para evaluar y predecir el estado de enteritis necrótica de las aves en el campo.

Determinants of lenalidomide response with or without erythropoiesis-stimulating agents in myelodysplastic syndromes: the HOVON89 trial.

A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).

Free neurovascular toe-(joint)-transfers compared to alternative reconstructive procedures for amputation injuries of two and tripartite fingers with substance loss.

BACKGROUND: Complex injuries of the hand frequently result in loss of essential functional features. Common reconstructive procedures for soft tissue defects of the thumb or phalanges are locoregional flaps like Moberg-, Foucher-, Cross-Finger- or Littler flaps. Microneurovascular toe (joint-) transfers complete the arsenal of operative reconstructive procedures and allow for most detailed reconstructions. Our experiences with free toe transplants are reported and diversely discussed regarding contending procedures. METHODS: From 2010 until 2019 14 patients who received emergency or elective partial or complete toe transfers were compared with a control group (n = 12) treated with contending reconstructive procedures. Aim of the reconstructions was to cover the defect with well-vascularized, sensate tissue, while preserving length and range of motion in a reliable manner. RESULTS: The Kapandji score showed a significant difference (p- value = 0.04) with a score of 9.8 in comparison to control group (Kapandji index = 8.0). CONCLUSION: In our heterogenic patient collective free toe transplants have proven to achieve comparable functional results for reconstruction of two and tripartite phalanxes as opposed to common local reconstructive procedures.

Does the built environment influence location- and trip-based sedentary behaviors? Evidence from a GPS-based activity space approach of neighborhood effects on older adults.

OBJECTIVE: Evidence on the influence of built environments on sedentary behaviors remains unclear and is often contradictory. The main limitations encompass the use of self-reported proxies of sedentary time (ST), the scarce consideration of the plurality of sedentary behaviors, and environmental exposures limited to the residential neighborhood. We investigated the relationships between GPS-based activity space measures of environmental exposures and accelerometer-based ST measured in total, at the place of residence, at all locations, and during trips. METHODS: This study is part of the CURHA project, based on 471 older adults residing in Luxembourg, who wore a GPS receiver and a tri-axial accelerometer during 7 days. Daily ST was computed in total, at the residence, at all locations and during trips. Environmental exposures included exposure to green spaces, walking, biking, and motorized transportation infrastructures. Associations between environments and ST were examined using linear and negative binomial mixed models, adjusted for demographics, self-rated health, residential self-selection, weather conditions and wear time. RESULTS: Participants accumulated, on average, 8 h and 14 min of ST per day excluding sleep time. ST spent at locations accounted for 83 % of the total ST. ST spent at the residence accounted for 87 % of the location-based ST and 71 % of the total ST. Trip-based ST represents 13 % of total ST, and 4 % remained unclassified. Higher street connectivity was negatively associated with total ST, while the density of parking areas correlated positively with total and location-based ST. Stronger associations were observed for sedentary bouts (uninterrupted ST over 20 and 30 min). CONCLUSION: Improving street connectivity and controlling the construction of new parking, while avoiding the spatial segregation of populations with limited access to public transport, may contribute to limit ST. Such urban planning interventions may be especially efficient in limiting the harmful uninterrupted bouts of ST among older adults.

Evolving Project ECHO: delivery of pediatric pain core competency learning for interprofessional healthcare providers.

Introduction: Healthcare providers (HCPs) practicing in community settings are critical to improving access to pain care, yet there are significant gaps in training opportunities designed for interprofessional learners. Project Extension for Community Healthcare Outcomes (Project ECHO®) is an established model for delivering online HCP education through virtual clinics and cultivating a community of practice. However, to our knowledge, the integration of pain core competency education into the ECHO® model has not been previously attempted. This innovation could enhance the ECHO® model while also addressing the growing calls for more accessible interprofessional pain curricula. This paper describes efforts to implement and evaluate core competency curricula within the context of Pediatric Project ECHO for Pain, one of the first pediatric-pain focused ECHO programs in the world. Methods: Needs assessments informed curricula development. The first delivered core competency model consisted of synchronous webinar-style sessions while the second model included a mixture of asynchronous (eLearning course) and synchronous (virtual clinical debrief) elements. A convenience sample of HCPs was recruited from ECHO program registrants. Participants completed baseline and follow-up surveys to assess core competency acceptability as well as impact on knowledge and self-efficacy related to managing pediatric pain. Usability of the eLearning platform (model 2 only) was also evaluated. Surveys used 5-point Likert scales to capture outcomes. A priori targets included mean scores ≥4/5 for acceptability and ≥80% of learners reporting knowledge and self-efficacy improvements. The study received local research ethics approval. Results: The core competency was found to be highly acceptable to interprofessional learners (n = 31) across delivery models, surpassing a priori targets. Specifically, it was characterized as a worthwhile and satisfactory experience that was helpful in supporting learning. The core competency was also associated with improvements in knowledge and self-efficacy by 97% and 90% of learners, respectively. The eLearning platform was reported to have high usability with clinically realistic cases (100% of respondents) that were helpful to inform care delivery (94% of respondents). Conclusion: The integration of core competency learning within the Project ECHO® model was a successful approach to deliver pediatric pain education to interprofessional HCPs.

Survival at older ages: are greater influenza antibody titers protective?

Antibodies are a core element of the immune system's defense against infectious diseases. We hypothesize that antibody titres might therefore be an important predictor of survival in older individuals. This is important because biomarkers that robustly measure survival have proved elusive, despite their potential utility in health care settings. We present evidence supporting the hypothesis that influenza antibody titres are associated with overall survival of older individuals, and indicate a role for biological sex in modulating this association. Since antibody titres can be modulated by vaccination, these results have important implications for public health policy on influenza control in aging populations.

Association of pre-radiotherapy tumour burden and overall survival in newly diagnosed glioblastoma adjusted for MGMT promoter methylation status.

PURPOSE: We retrospectively evaluated the association between postoperative pre-radiotherapy tumour burden and overall survival (OS) adjusted for the prognostic value of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation in patients with newly diagnosed glioblastoma treated with radio-/chemotherapy with temozolomide. MATERIALS AND METHODS: Patients were included from the CENTRIC (EORTC 26071-22072) and CORE trials if postoperative magnetic resonance imaging scans were available within a timeframe of up to 4weeks before radiotherapy, including both pre- and post-contrast T1w images and at least one T2w sequence (T2w or T2w-FLAIR). Postoperative (residual) pre-radiotherapy contrast-enhanced tumour (CET) volumes and non-enhanced T2w abnormalities (NT2A) tissue volumes were obtained by three-dimensional segmentation. Cox proportional hazard models and Kaplan Meier estimates were used to assess the association of pre-radiotherapy CET/NT2A volume with OS adjusted for known prognostic factors (age, performance status, MGMT status). RESULTS: 408 tumour (of which 270 MGMT methylated) segmentations were included. Median OS in patients with MGMT methylated tumours was 117 weeks versus 61weeks in MGMT unmethylated tumours (p < 0.001). When stratified for MGMT methylation status, higher CET volume (HR 1.020; 95% confidence interval CI [1.013-1.027]; p < 0.001) and older age (HR 1.664; 95% CI [1.214-2.281]; p = 0.002) were significantly associated with shorter OS while NT2A volume and performance status were not. CONCLUSION: Pre-radiotherapy CET volume was strongly associated with OS in patients receiving radio-/chemotherapy for newly diagnosed glioblastoma stratified by MGMT promoter methylation status.

Impact of Bepanthen® and dexpanthenol on human nasal ciliary beat frequency in vitro.

BACKGROUND: Dexpanthenol-containing ointments/fluids are recommended to restore impaired nasal mucosa. To date, there are no data about the influence of dexpanthenol or formulations including dexpanthenol on ciliary beat frequency (CBF) of nasal epithelial cells. METHODS: We tested the ciliary beat frequency of human nasal epithelial cells in RPMI 1640 cell solution using in vitro high-frequency video microscopy every 60 s over a period of 15 min (min). Bepanthen® solution and dexpanthenol in two clinically relevant concentrations (1.67% and 3.33%) were added to the cells. Addition of sterile water served as control group. To get a better overview, the measurements after 1 min, 5 min and 15 min were combined. RESULTS: The CBF in the control group (n = 17) after 15 min was 7.3 ± 2.6 Hz. In comparison, the CBF after 15 min was 1.8 ± 1.0 Hz in the 3.33% Bepanthen® group (n = 17) and 3.2 ± 1.2 Hz in the 1.67% group, which was statistically significantly lower in both groups (p < 0.001). With regard to the dexpanthenol group (n = 17) a CBF of 6.0 ± 2.6 Hz with 3.33% and 6.1 ± 2.4 Hz with 1.67% dexpanthenol, was detected, which was again statistically significantly lower (p = 0.06) compared to the control group except CBF at 15 min with 1.57% (n = 17; p = 0.04). In general, the effect on CBF was less pronounced with dexpanthenol compared with Bepanthen® with a statistically significant difference between the two formulations. The results were verified by calculating an analysis of variance (ANOVA). CONCLUSIONS: Bepanthen® as an ointment, solution or inhalation is commonly used in ENT for mucosal care. Our results have shown that both substances reduce CBF in clinically relevant concentrations, although the effect was more pronounced with Bepanthen® compared to dexpanthenol solution, which could be related to additives or change of physical properties in the solution. Further research is needed to assess potential clinical relevance.

Pediatric Project ECHO® for Pain: implementation and mixed methods evaluation of a virtual medical education program to support interprofessional pain management in children and youth.

BACKGROUND: Pediatric pain is a complex health challenge requiring a multi-modal management approach. It is critical that healthcare providers (HCPs) have access to ongoing, flexible education and mentorship specific to pediatric pain. However, there are significant gaps in available pain education and a need for more opportunities to support interprofessional training. Project Extension for Community Healthcare Outcomes (Project ECHO®) is a model for delivering online HCP education and cultivating a virtual community of practice. Within the pediatric pain setting, ECHO® has potential to improve local access to specialized pain knowledge, particularly among the physicians, nurses, and allied health providers who primarily manage these cases in community and hospital settings across rural and urban environments. The purpose of this study was three-fold. First, to evaluate the feasibility (participation levels, acceptability) of implementing Project ECHO® in the context of pediatric pain. Second, to measure preliminary program impacts on HCP knowledge, self-efficacy, and clinical practice. Third, to characterize HCP program engagement levels before and after onset of the COVID-19 pandemic. METHODS: A needs assessment was conducted to identify interprofessional education gaps and inform the program curriculum. The no-cost Pediatric ECHO® for Pain program offered TeleECHO sessions (didactic and case-based learning) as well as foundational education. Surveys were distributed at baseline and 6 months to assess outcomes using 7-point Likert scales. Participant engagement was assessed for periods prior to and during the COVID-19 pandemic. Descriptive and inferential statistical analyses were conducted. RESULTS: Eighty-five TeleECHO sessions were hosted, with a mean attendance of 34.1 ± 23.4 HCPs. Acceptability scores at 6 months (n = 33) ranged from 5.0 ± 1.4 to 6.5 ± 0.5. Participants reported statistically significant (p < 0.05) improvements in knowledge (7 out of 7 topics) and self-efficacy (8 out of 9 skills). Most participants reported positive practice impacts, including improved satisfaction with managing children with pain. Exploratory analyses showed a trend of greater engagement from ECHO® learners after onset of the COVID-19 pandemic. CONCLUSIONS: Project ECHO® is a feasible and impactful model for virtual education of interprofessional HCPs in managing pediatric pain.

dtiRIM: A generalisable deep learning method for diffusion tensor imaging.

Diffusion weighted MRI is an indispensable tool for routine patient screening and diagnostics of pathology. Recently, several deep learning methods have been proposed to quantify diffusion parameters, but poor generalisation to new data prevents broader use of these methods, as they require retraining of the neural network for each new scan protocol. In this work, we present the dtiRIM, a new deep learning method for Diffusion Tensor Imaging (DTI) based on the Recurrent Inference Machines. Thanks to its ability to learn how to solve inverse problems and to use the diffusion tensor model to promote data consistency, the dtiRIM can generalise to variations in the acquisition settings. This enables a single trained network to produce high quality tensor estimates for a variety of cases. We performed extensive validation of our method using simulation and in vivo data, and compared it to the Iterated Weighted Linear Least Squares (IWLLS), the approach of the state-of-the-art MRTrix3 software, and to an implementation of the Maximum Likelihood Estimator (MLE). Our results show that dtiRIM predictions present low dependency on tissue properties, anatomy and scanning parameters, with results comparable to or better than both IWLLS and MLE. Further, we demonstrate that a single dtiRIM model can be used for a diversity of data sets without significant loss in quality, representing, to our knowledge, the first generalisable deep learning based solver for DTI.

A favorable donor site in microsurgery: Nerve and vein graft harvest from the dorsum of the foot.

BACKGROUND AND OBJECTIVES: In complex hand traumas nerves and vessels are often destructed without the possibility for primary repair. For bridging defects of nerves, veins and arteries grafts are necessary. Commonly nerve and vein grafts from adjacent donor sites as the wrist, forearm or cubital region are harvested. METHODS: This study is a retrospective cohort study. Between 2017 and 2019, 10 patients with complex hand injuries were treated. There were 8 males and 2 females, with an average age of 39 years (range 8-63 years). In all cases grafts were used of the dorsum of the foot for reconstructing of the severed digital nerves and arteries. All donor sites could be closed primarily. RESULTS: In 100% of cases nerves and veins of the dorsum of the foot showed a good size match as well as adequate length for a sufficient repair. The overall Hand Injury Severity Score (HISS) was determined with a median of 86 (range 57 to 286). In the area of the donor site no relevant complications were seen. CONCLUSIONS: In complex hand injuries the dorsum of the foot is a favorable donor site for nerve and vein graft harvest.

Covering of wound infection in hip arthroplasty with local cutaneous flaps.

Total hip arthroplasty is a very common procedure to treat osteoarthritis. One of the complication is the infection which occurs in about 1% of the cases. The manifestation of infection can be poor wound healing with dehiscence and exposition of bone or prosthetic components. Hip arthroplasty infections are difficult to treat. It required an associated multidisciplinary approach with infectiology, orthopedic and plastic surgeries. The study included five patients with hip wound dehiscence after total hip arthroplasty. Coverage after orthopedic surgery was provided by local cutaneous flap. These cutaneous flaps were either a deep inferior epigastric perforator flap (DIEP) or a transposition flap. The orthopedic and the plastic treatment were done at the same time. Two deep inferior epigastric flaps were performed for patients with a deep defect with bone or prosthesis exposure. Four transposition flaps were done in three patients with wound dehiscence but without direct contact with the prosthesis. Three transposition flaps were done from the abdominal wall and one from the posterior thigh. The mean follow up was 18 months, ranging from 10 to 24months. After healing, there was no recurrence of the infection. In all cases, the coverage was obtained. The prosthesis was salvage and the gait was possible. Cutaneous flaps are easy and safe to cover the hip. They are reliable flaps even in patients with multiple co-morbidities. They do not cause sequelae on the recipient site. This study is the first about cutaneous flap for covering hip defects in hip arthroplasty infections.

The KNee OsteoArthritis Prediction (KNOAP2020) challenge: An image analysis challenge to predict incident symptomatic radiographic knee osteoarthritis from MRI and X-ray images.

OBJECTIVES: The KNee OsteoArthritis Prediction (KNOAP2020) challenge was organized to objectively compare methods for the prediction of incident symptomatic radiographic knee osteoarthritis within 78 months on a test set with blinded ground truth. DESIGN: The challenge participants were free to use any available data sources to train their models. A test set of 423 knees from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study consisting of magnetic resonance imaging (MRI) and X-ray image data along with clinical risk factors at baseline was made available to all challenge participants. The ground truth outcomes, i.e., which knees developed incident symptomatic radiographic knee osteoarthritis (according to the combined ACR criteria) within 78 months, were not provided to the participants. To assess the performance of the submitted models, we used the area under the receiver operating characteristic curve (ROCAUC) and balanced accuracy (BACC). RESULTS: Seven teams submitted 23 entries in total. A majority of the algorithms were trained on data from the Osteoarthritis Initiative. The model with the highest ROCAUC (0.64 (95% confidence interval (CI): 0.57-0.70)) used deep learning to extract information from X-ray images combined with clinical variables. The model with the highest BACC (0.59 (95% CI: 0.52-0.65)) ensembled three different models that used automatically extracted X-ray and MRI features along with clinical variables. CONCLUSION: The KNOAP2020 challenge established a benchmark for predicting incident symptomatic radiographic knee osteoarthritis. Accurate prediction of incident symptomatic radiographic knee osteoarthritis is a complex and still unsolved problem requiring additional investigation.

Current advances on Talbot-Lau x-ray imaging diagnostics for high energy density experiments (invited).

Talbot-Lau x-ray interferometry is a refraction-based diagnostic that can map electron density gradients through phase-contrast methods. The Talbot-Lau x-ray deflectometry (TXD) diagnostics have been deployed in several high energy density experiments. To improve diagnostic performance, a monochromatic TXD was implemented on the Multi-Tera Watt (MTW) laser using 8 keV multilayer mirrors (Δθ/θ = 4.5%-5.6%). Copper foil and wire targets were irradiated at 1014-1015 W/cm2. Laser pulse length (∼10 to 80 ps) and backlighter target configurations were explored in the context of Moiré fringe contrast and spatial resolution. Foil and wire targets delivered increased contrast <30%. The best spatial resolution (<6 µm) was measured for foils irradiated 80° from the surface. Further TXD diagnostic capability enhancement was achieved through the development of advanced data postprocessing tools. The Talbot Interferometry Analysis (TIA) code enabled x-ray refraction measurements from the MTW monochromatic TXD. Additionally, phase, attenuation, and dark-field maps of an ablating x-pinch load were retrieved through TXD. The images show a dense wire core of ∼60 µm diameter surrounded by low-density material of ∼40 µm thickness with an outer diameter ratio of ∼2.3. Attenuation at 8 keV was measured at ∼20% for the dense core and ∼10% for the low-density material. Instrumental and experimental limitations for monochromatic TXD diagnostics are presented. Enhanced postprocessing capabilities enabled by TIA are demonstrated in the context of high-intensity laser and pulsed power experimental data analysis. Significant advances in TXD diagnostic capabilities are presented. These results inform future diagnostic technique upgrades that will improve the accuracy of plasma characterization through TXD.

Addition of the nuclear export inhibitor selinexor to standard intensive treatment for elderly patients with acute myeloid leukemia and high risk myelodysplastic syndrome.

Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65-80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1-24. In the second cycle, cytarabine 1000 mg/m2 twice daily, days 1-6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69-91%) vs. 59% (45-72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively (p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl ).

Assessment of automated craving across substances and across cultures: stability-analysis of the Craving Automated Scale (CAS).

BACKGROUND: The transition from hedonic to compulsive use in Substance Use Disorders (SUD) is a critical point in SUD progression and hence relevant for assessment and treatment. To measure the habitual patterns of substance consumption, the Craving Automated Scales (CAS) for alcohol (CAS-A), substances (CAS-S) and cigarette smoking (CAS-CS) were developed and introduced to different countries. In this study, we aimed to investigate the structural stability of CAS across substances and cultures. METHODS: This study analyzed the CAS-scores of a sample of 370 participants in Germany, China and the UK, including 262 opioid-users, 65 smokers and 43 alcohol-users. We performed stability analyses to check the stability (i. e. factorial invariance) of factor solutions. Based on confirmed stability of the general factor (gfactor) solution and the calculations rule obtained in the previous validation of CAS-alcohol (CAS-A), the factor structures of CAS-A, CAS-S and CAS-CS were compared. RESULTS: The gfactor solutions based on calculations rule shows good stability, with the mean stability coefficients of 0.990 and 0.977 for CAS-S and CAS-CS respectively. The gfactor patterns were similar for CAS-A, CAS-S and CAS-CS, as well as across samples (Germany, China and the UK), with most factor-loadings larger than 0.7. Based on these findings, CAS-S and CAS-CS were also associated with established clinical measures of SUD. CONCLUSIONS: Our findings suggest the two-gfactor solution based on a proposed calculation rule has a high stability across substances and cultures. This could be in line with common neurobiological mechanisms underlying habitual substance use. Moreover, comparing CAS with established clinical tools suggests that CAS might assess the automated behavior in substance consumption in a more sophisticated way.

• The two-gfactor solution of the Craving Automated Scale has a good stability.• The Craving Automated Scale can be used across substances.• The Craving Automated Scale is associated with established SUD measures.

Differences Between MR Brain Region Segmentation Methods: Impact on Single-Subject Analysis.

For the segmentation of magnetic resonance brain images into anatomical regions, numerous fully automated methods have been proposed and compared to reference segmentations obtained manually. However, systematic differences might exist between the resulting segmentations, depending on the segmentation method and underlying brain atlas. This potentially results in sensitivity differences to disease and can further complicate the comparison of individual patients to normative data. In this study, we aim to answer two research questions: 1) to what extent are methods interchangeable, as long as the same method is being used for computing normative volume distributions and patient-specific volumes? and 2) can different methods be used for computing normative volume distributions and assessing patient-specific volumes? To answer these questions, we compared volumes of six brain regions calculated by five state-of-the-art segmentation methods: Erasmus MC (EMC), FreeSurfer (FS), geodesic information flows (GIF), multi-atlas label propagation with expectation-maximization (MALP-EM), and model-based brain segmentation (MBS). We applied the methods on 988 non-demented (ND) subjects and computed the correlation (PCC-v) and absolute agreement (ICC-v) on the volumes. For most regions, the PCC-v was good ( > 0.75 ), indicating that volume differences between methods in ND subjects are mainly due to systematic differences. The ICC-v was generally lower, especially for the smaller regions, indicating that it is essential that the same method is used to generate normative and patient data. To evaluate the impact on single-subject analysis, we also applied the methods to 42 patients with Alzheimer's disease (AD). In the case where the normative distributions and the patient-specific volumes were calculated by the same method, the patient's distance to the normative distribution was assessed with the z-score. We determined the diagnostic value of this z-score, which showed to be consistent across methods. The absolute agreement on the AD patients' z-scores was high for regions of thalamus and putamen. This is encouraging as it indicates that the studied methods are interchangeable for these regions. For regions such as the hippocampus, amygdala, caudate nucleus and accumbens, and globus pallidus, not all method combinations showed a high ICC-z. Whether two methods are indeed interchangeable should be confirmed for the specific application and dataset of interest.