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Abstract Transarterial radioembolization (TARE) is a well‐established therapy for intermediate and advanced tumor stages of hepatocellular carcinoma (HCC). Treatment‐associated toxicities are rare. Previous studies have outlined that the prognosis after TARE is determined primarily by tumor stage and liver function. The subset of patients benefiting from TARE remains to be defined. Sixty‐one patients with HCC treated with TARE between 2015 and 2020 were retrospectively included in the study. Hepatic decompensation was defined as an increase of bilirubin or newly developed ascites that was not explained by tumor progression within 3 months after TARE. Predictive factors of hepatic decompensation and prognostic factors were assessed. Hepatic decompensation was observed in 27.9% (n = 17) of TARE‐treated patients during follow‐up. Albumin‐bilirubin (ALBI) score at baseline and radiation dose on nontumor liver proved to be independent risk factors for the development of hepatic decompensation in multivariable regression models (ALBI score: odds ratio [OR] 6.425 [1.735;23.797], p

Transarterial radioembolization is a well-established method for the treatment of hepatocellular carcinoma. The tolerability and incidence of hepatic decompensation are related to the doses delivered to the tumor and healthy liver. This retrospective study was performed at our center to evaluate whether tumor- and healthy-liver-absorbed dose levels in TARE are predictive of tumor response according to the mRECIST 1.1 criteria and overall survival. One hundred and six patients with hepatocellular carcinoma were treated with [90Y]-loaded resin microspheres and completed the follow-up. The dose delivered to each compartment was calculated using a compartmental model. The model was based on [99mTc]-labelled albumin aggregate images obtained before the start of therapy. Tumor response was assessed after three months of treatment. Kaplan-Meier analysis was used to assess survival. The mean age of our population was 66 ± 13 years with a majority being BCLC B tumors. Forty-two patients presented with portal vein thrombosis. The response rate was 57% in the overall population and 59% in patients with thrombosis. Target-to-background (TBR) values measured on initial [99mTc]MAA-SPECT-imaging and tumor model dosimetric values were associated with tumor response (p < 0.001 and p = 0.009, respectively). A dosimetric threshold of 136.5 Gy was predictive of tumor response with a sensitivity of 84.2% and specificity of 89.4%. Overall survival was 24.1 months [IQR 13.1–36.4] for patients who responded to treatment compared to 10.4 months [IQR 6.3–15.9] for the remaining patients (p = 0.022). In this cohort, the initial [99mTc]MAA imaging is predictive of response and survival. The dosimetry prior to the application of TARE can be used for treatment planning and our results also suggest that the therapy is well-tolerated. In particular, hepatic decompensation can be predicted even in the presence of PVT.

Anomaly detection is essential for realizing modern and secure cyber-physical production systems. By detecting anomalies, there is the possibility to recognize, react early, and in the best case, fix the anomaly to prevent the rise or the carryover of a failure throughout the entire manufacture. While current centralized methods demonstrate good detection abilities, they do not consider the limitations of industrial setups. To address all these constraints, in this study, we introduce an unsupervised, decentralized, and real-time process anomaly detection concept for cyber-physical production systems. We employ several 1D convolutional autoencoders in a sliding window approach to achieve adequate prediction performance and fulfill real-time requirements. To increase the flexibility and meet communication interface and processing constraints in typical cyber-physical production systems, we decentralize the execution of the anomaly detection into each separate cyber-physical system. The installation is fully automated, and no expert knowledge is needed to tackle data-driven limitations. The concept is evaluated in a real industrial cyber-physical production system. The test result confirms that the presented concept can be successfully applied to detect anomalies in all separate processes of each cyber-physical system. Therefore, the concept is promising for decentralized anomaly detection in cyber-physical production systems.

Background To provide insight into bone turnover, quantitative measurements of bone remodeling are required. Radionuclide studies are widely used in clinical care, but have been rarely used in the exploration of the bone in preclinical studies. We describe a bone planar scintigraphy method for frequent assessment of bone activity in mice across the growing period. Since repeated venous radiotracer injections are hardly feasible in mice, we investigated the subcutaneous route. Methods Repeated 99mTc-hydroxymethylene diphosphonate (HMDP) tracer bone planar scintigraphy studies of the knee region and µCT to measure femur growth rate were performed in eight mice between week 6 and week 27 of life, i.e., during their growth period. Three independent investigators assessed the regions of interest (ROI). An index was calculated based on the counts in knees ROI (normalized by pixels and seconds), corrected for the activity administered, the decay between administration and imaging, and individual weights. Results A total of 93 scintigraphy studies and 85 µCT were performed. Repeated subcutaneous tracer injections were well tolerated and allowed for adequate radionuclide studies. Mean scintigraphic indexes in the knees ROI decreased from 87.4 ± 2.6 × 10−6 counts s−1 pixel−1 MBq−1 g−1 at week 6 to 15.0 ± 3.3 × 10−6 counts s−1 pixel−1 MBq−1 g−1 at week 27. The time constant of the fitted exponential decay was equal to 23.5 days. As control mean femur length assessed by µCT increased from 12.2 ± 0.8 mm at week 6 to 15.8 ± 0.2 mm at week 22. The time constant of the fitted Gompertz law was equal to 26.7 days. A correlation index of −0.97 was found between femur growth and decrease of bone tracer activity count between week 6 and 24. Conclusion This methodological study demonstrates the potential of repeated bone planar scintigraphy in growing mice, with subcutaneous route for tracer administration, for quantitative assessment of bone remodeling.

The aim of this prospective observational trial was to evaluate the efficacy, toxicity and quality of life after stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC) and to assess the results of this treatment in comparison to trans-arterial chemoembolization (TACE). Patients with HCC, treated with TACE or SBRT, over a period of 12 months, enrolled in the study. The primary endpoint was feasibility; secondary endpoints were toxicity, quality of life (QOL), local progression (LP) and overall survival (OS). Between 06/2016 and 06/2017, 19 patients received TACE and 20 SBRT, 2 of whom were excluded due to progression. The median follow-up was 31 months. The QOL remained stable before and after treatment and was comparable in both treatment groups. Five patients developed grade ≥ 3 toxicities in the TACE group and 3 in the SBRT group. The cumulative incidence of LP after 1-, 2- and 3-years was 6, 6, 6% in the SBRT group and 28, 39, and 65% in the TACE group (p = 0.02). The 1- and 2- years OS rates were 84% and 47% in the TACE group and 44% and 39% in the SBRT group (p = 0.20). In conclusion, SBRT is a well-tolerated local treatment with a high local control rates and can be safely delivered, while preserving the QOL of HCC patients.

Abstract Background The implementation of person-centred, need-oriented and flexible care for people with substance-related problems is often insufficient, in large part due to the complexity of addiction support services among different providers. A standardized online assessment and subsequent sector-independent treatment coordination could provide individuals with more appropriate services, thereby making better use of individual services and leading to a more effective addiction support system as a whole. The aim of this study is to determine the effectiveness and cost-effectiveness of sector-independent treatment coordination following an online assessment, in comparison with the current standard of care and treatment process in Germany. Methods The sample size of this randomized, controlled trial has been set to a total of 400 participants with substance-related problems. Participants living in Stuttgart, Germany, will be randomly allocated to (1) the intervention group with immediate online assessment and subsequent sector-independent treatment coordination (ASSIST) or (2) the waitlist group. Participants in the waitlist group will initially remain in usual care and only be provided with the online assessment 6 months later. Short-term effects (over 2 months) and medium-term effects (over 6 months) of ASSIST will be compared between the intervention and the waitlist groups. The primary outcome is improved treatment satisfaction. Secondary outcomes include improved subjective quality of life and empowerment, reductions in patients’ substance use, unmet needs and illness-related clinical and social impairment. Health economic evaluation as well as quantitative and qualitative process evaluations will be conducted. Discussion The results of this study are expected to provide information on whether sector-independent treatment coordination following an online assessment contributes to improved health care service provision for people with substance-related problems. This randomized controlled trial will help identify facilitators and barriers to the sustainable implementation of a cross-sectoral care concept in substance abuse services. Trial registration German Clinical Trial Register DRKS00026996 . Registered on 29 October 2021

Abstract Background This systematic review investigated the efficacy and safety of surgical procedures augmented with cell therapies for chondral defects of the talus. Methods The present systematic review was conducted according to the 2020 PRISMA guidelines. PubMed, Google scholar, Embase, and Scopus databases were accessed in March 2022. All the clinical trials investigating surgical procedures for talar chondral defects augmented with cell therapies were accessed. The outcomes of interest were to investigate whether surgical procedures augmented with cell therapies promoted improvement in patients reported outcomes measures (PROMs) with a tolerable rate of complications. Results Data from 477 procedures were retrieved. At a mean follow-up of 34.8 ± 9.7 months, the Visual Analogic Scale (VAS) improved of 4.4/10 (P = 0.002) and the American Orthopaedic Foot and Ankle Score (AOFAS) of 31.1/100 (P = 0.0001) points. No improvement was found in Tegner score (P = 0.4). Few articles reported data on complications. At last follow-up, the rate of reoperation and failure were 0.06% and 0.03%, respectively. No graft delamination or hypertrophy was observed. Conclusion The current evidence suggests that cell therapies may be effective and safe to enhance surgical procedures for chondral defects of the talus. These results should be considered within the limitations of the present study. The current literature should be enriched with randomized controlled clinical trials with larger population size and longer follow-up.

Abstract Background Congenital bladder exstrophy is a rare malformation which is often associated with pubic diastasis and hip dysplasia. We reported the case two patients who underwent total hip arthroplasty (THA) due to advanced osteoarthritis combined with large congenital pubic diastasis (> 10 cm). Case presentation The first patient, a 39 years old woman with a pubic diastase and severe hip dysplasia on both sides was treated with a primary two-staged bilateral THA. Both hips were treated with a cementless osteoconductive cup (TM, Zimmer-Biomet) and a cementless stem (Alloclassic SL, Zimmer-Biomet). A 10° elevated rim liner of the cup was used in order to avoid dislocation. The main problem was represented by the fixation of the cup, given the retroverted acetabulum along with the elevated rotation centre due to the dysplastic hips. In the case two, a 52 years woman presented dysplastic osteoarthritis of the left hip. A conventional hemispherical cup (Alloclassic-Allofit, Zimmer-Biomet) was placed in the retroverted acetabulum combined with a cementless stem (Fitmore A, Zimmer-Biomet) attached at the metaphyseal proximal femur bone. Conclusion Our results suggest that THA may be a good strategy to manage advanced hip osteoarthritis in patients with dysplasia and congenital pubic diastasis. Level of evidence IV, case series.

Introduction. Reconstruction of acetabular bone defects by the combination of trabecular metal augments and porous cups can be complex when extensive bone loss and poor-quality bone exists. The onset of porous cups with an interlocking mechanism may simplify surgical technique due to its superior initial mechanical stability. We endorse the possibility for a change in the classical order of setting of the augments and the cup. Methods. We present a technical modification and a series of cases of three patients with Paprosky IIB and IIIA acetabular defects operated with a combination of porous metal augments and a porous cup. In all the three patients, the setting of the cup was done first and secured with locked screws, and then the augments were set in place as a wedge and fixed with screws in a standard fashion. Results. The postoperative X-ray showed good position of implants with restoration of the center of rotation, and the patients had good recovery. Radiological evaluation in the midterm follow-up did not show mobilization of implants. Discussion. The use of metal porous augments is widely used for severe acetabular defects, being a versatile system to adapt to the different size defects. Nevertheless, its use may be technically demanding and time consuming. It is not infrequent that the setting of the augments conditions the final position of the cup with a possible interference with initial stability and eventually bone ingrowth of the cup. The interlocking mechanism offers an additional biomechanical stability and thus may allow us to place the cup first in the desired position with a less demanding technique. Conclusion. With the use of locked-screw porous metal cups, the order of setting of implants may be changed in order to obtain a better restoration of the center of rotation and increased host-bone implant contact with a simplified surgical technique.

Abstract Background Public health measures to curb SARS-CoV-2 transmission rates may have negative psychosocial consequences in youth. Digital interventions may help to mitigate these effects. We investigated the associations between social isolation, COVID-19-related cognitive preoccupation, worries, and anxiety, objective social risk indicators, and psychological distress, as well as use of, and attitude toward, mobile health (mHealth) interventions in youth. Methods Data were collected as part of the “Mental Health And Innovation During COVID-19 Survey”—a cross-sectional panel study including a representative sample of individuals aged 16–25 years (N = 666; Mage = 21.3; assessment period: May 5, 2020 to May 16, 2020). Results Overall, 38% of youth met criteria for moderate or severe psychological distress. Social isolation worries and anxiety, and objective risk indicators were associated with psychological distress, with evidence of dose–response relationships for some of these associations. For instance, psychological distress was progressively more likely to occur as levels of social isolation increased (reporting “never” as reference group: “occasionally”: adjusted odds ratio [aOR] 9.1, 95% confidence interval [CI] 4.3–19.1, p

Abstract  Magnetic resonance elastography (MRE) is an increasingly used method for non-invasive determination of tissue stiffness. MRE has shown its ability to measure in vivo elasticity or viscoelasticity depending on the chosen rheological model. However, few data exist on quantitative comparison of MRE with reference mechanical measurement techniques. MRE has only been validated on soft homogeneous gels under both Hookean elasticity and linear viscoelasticity assumptions, but comparison studies are lacking concerning viscoelastic properties of complex heterogeneous tissues. In this context, the present study aims at comparing an MRE-based method combined with a wave equation inversion algorithm to rotational rheometry. For this purpose, experiments are performed on in vitro porcine brain tissue. The dynamic behavior of shear storage (G') and loss (G '') moduli obtained by both rheometry and MRE at different frequency ranges is similar to that of linear viscoelastic properties of brain tissue found in other studies. This continuity between rheometry and MRE results consolidates the quantitative nature of values found by MRE in terms of viscoelastic parameters of soft heterogeneous tissues. Based on these results, the limits of MRE in terms of frequency range are also discussed. [ABSTRACT FROM AUTHOR]