Efficiency of succinylated gelatin and amino acid infusions for kidney uptake reduction of radiolabeled αvß6-integrin targeting peptides: considerations on clinical safety profiles.

PURPOSE: 68Ga-Trivehexin is an investigational PET radiopharmaceutical (NCT05799274) targeting αvß6-integrin for PET imaging of carcinomas. 177Lu-D0301 is a structurally related therapeutic peptide tetramer. However, it showed considerable kidney uptake in rodents, impeding clinical applicability. We therefore evaluated the impact of different kidney protection strategies on the biodistribution of both agents in normal and tumor-bearing mice. METHODS: Ex-vivo biodistribution of 68Ga-Trivehexin (90 min p.i.) and 177Lu-D0301 (90 min and 24 h p.i.) was determined in healthy C57BL/6N and H2009 (human lung adenocarcinoma) xenografted CB17-SCID mice without and with co-infusion of 100 µL of solutions containing 2.5% arginine + 2.5% lysine (Arg/Lys), 4% succinylated gelatin (gelofusine, gelo), or combinations thereof. Arg/Lys was injected either i.p. 30 min before and after the radiopharmaceutical, or i.v. 2 min before the radiopharmaceutical. Gelo was administered either i.v. 2 min prior activity, or pre-mixed and injected together with the radiopharmaceutical (n = 5 per group). C57BL/6N mice were furthermore imaged by PET (90 min p.i.) and SPECT (24 h p.i.). RESULTS: Kidney uptake of 68Ga-Trivehexin in C57BL/6N mice was reduced by 15% (Arg/Lys i.p.), 25% (Arg/Lys i.v.), and 70% (gelo i.v.), 90 min p.i., relative to control. 177Lu-D0301 kidney uptake was reduced by 2% (Arg/Lys i.p.), 41% (Arg/Lys i.v.), 61% (gelo i.v.) and 66% (gelo + Arg/Lys i.v.) 24 h p.i., compared to control. Combination of Arg/Lys and gelo provided no substantial benefit. Gelo furthermore reduced kidney uptake of 177Lu-D0301 by 76% (90 min p.i.) and 85% (24 h p.i.) in H2009 bearing SCID mice. Since tumor uptake was not (90 min p.i.) or only slightly reduced (15%, 24 h p.i.), the tumor/kidney ratio was improved by factors of 3.3 (90 min p.i.) and 2.6 (24 h p.i.). Reduction of kidney uptake was demonstrated by SPECT, which also showed that the remaining activity was located in the cortex. CONCLUSIONS: The kidney uptake of both investigated radiopharmaceuticals was more efficiently reduced by gelofusine (61-85%) than Arg/Lys (25-41%). Gelofusine appears particularly suitable for reducing renal uptake of αvß6-integrin targeted 177Lu-labeled peptide multimers because its application led to approximately three times higher tumor-to-kidney ratios. Since the incidence of severe adverse events (anaphylaxis) with succinylated gelatin products (reportedly 0.0062-0.038%) is comparable to that of gadolinium-based MRI or iodinated CT contrast agents (0.008% and 0.04%, respectively), clinical use of gelofusine during radioligand therapy appears feasible if similar risk management strategies as for contrast agents are applied.

Health-related quality of life (EQ-5D) after revision arthroplasty following periprosthetic femoral fractures Vancouver B2 and B3 in geriatric trauma patients.

INTRODUCTION: The aim of this study was to determine the outcome parameters of revision arthroplasties for periprosthetic femoral fractures (PPFF) with a particular attention to quality of life (QoL) and mobility. MATERIALS AND METHODS: Retrospective single-center study of PPFF with loose implants that underwent revision arthroplasty. Depending on individual patient characteristics, either an uncemented or cemented revision stem was chosen. Data collection included demographics, complications, clinical course and outcome parameters. Follow-up took place at least one year postoperatively. RESULTS: Between 2008 and 2016, 43 patients could be included. Most patients (63%) were able to walk independently or with a walking aid after one year and amongst the surveyed patients 77% were able to reside at home. Concerning the QoL assessment, a high index of 0.8 ± 0.1 has been reached after one year. Mortality pointed out to be 9% after one year and 28% in general. CONCLUSION: The treatment of PPFF remains challenging. Although complication rates and mortality are high in this frail collective of geriatric patients, revision arthroplasty leads to good postoperative results regarding mobility and quality of life.

Effect of Cholesterol on the Structure and Composition of Glyco-DIBMA Lipid Particles.

Different amphiphilic co-polymers have been introduced to produce polymer-lipid particles with nanodisc structure composed of an inner lipid bilayer and polymer chains self-assembled as an outer belt. These particles can be used to stabilize membrane proteins in solution and enable their characterization by means of biophysical methods, including small-angle X-ray scattering (SAXS). Some of these co-polymers have also been used to directly extract membrane proteins together with their associated lipids from native membranes. Styrene/maleic acid and diisobutylene/maleic acid are among the most commonly used co-polymers for producing polymer-lipid particles, named SMALPs and DIBMALPs, respectively. Recently, a new co-polymer, named Glyco-DIBMA, was produced by partial amidation of DIBMA with the amino sugar N-methyl-d-glucosamine. Polymer-lipid particles produced with Glyco-DIBMA, named Glyco-DIBMALPs, exhibit improved structural properties and stability compared to those of SMALPs and DIBMALPs while retaining the capability of directly extracting membrane proteins from native membranes. Here, we characterize the structure and lipid composition of Glyco-DIBMALPs produced with either 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). Glyco-DIBMALPs were also prepared with mixtures of either POPC or DMPC and cholesterol at different mole fractions. We estimated the lipid content in the Glyco-DIBMALPs and determined the particle structure and morphology by SAXS. We show that the Glyco-DIBMALPs are nanodisc-like particles whose size and shape depend on the polymer/lipid ratio. This is relevant for designing nanodisc particles with a tunable diameter according to the size of the membrane protein to be incorporated. We also report that the addition of >20 mol % cholesterol strongly perturbed the formation of Glyco-DIBMALPs. Altogether, we describe a detailed characterization of the Glyco-DIBMALPs, which provides relevant inputs for future application of these particles in the biophysical investigation of membrane proteins.

The Impact of Digital Transformation on Blood Donation and Donor Characteristics.

Introduction: The management of an adequate donor pool is a constant and challenging task for blood centers in order to provide blood supply. New methods are required to streamline processes and attract (new) donors on a sustained basis. We present a digitalization method without media disruption and show the impact on our donors and their behavior. Methods: We designed and created a blood donation app that is fully compliant to all regulations and conforms to donor expectations. The presented digitalization serves the donor from preparation before the donation (health questionnaire) until completion of laboratory testing (medical report). Many other features are included and continuously attract donors to engage with the blood donation topic. Results: Eighteen months after the launch of our app, there are already 45,000 users. The digital questionnaire reduced the number of deferrals by 31.9% compared to the conventional paper questionnaire. Digital adopters show a significantly shorter donation interval (193 days compared to 316 days). In-app incentives include identification card, rapid laboratory testing results (time-to-results are two business days for 95%), and collection of badges among others. Conclusion: The presented method has changed our donor pool. Besides that, medical staff benefits from the automated process that allows focusing on the donor and their admission. On the other hand, the app has become a valid tool to manage our donor pool and attract first-time and young donors.

Self-rated health status and activities of daily living in the first 12 months after fragility fractures of the pelvis-a prospective study on 134 patients.

The aim of this study was to evaluate changes in activities of daily living and self-reported health status in the first year after fragility fractures of the pelvis. We found out that these fractures lead to a significant, long-lasting deterioration of both parameters, comparable with hip fractures. PURPOSE: The aim of this prospective study was to evaluate the development and to identify influencing factors in activities of daily living (ADL) and self-reported health status (HS) in the first year after fragility fractures of the pelvis (FFP). METHODS: A total of 134 patients with FFP ≥ 60 years were included. ADL were measured using the Barthel index (BI) and the IADL scale pre-fracture, at 6 weeks, 6 months, and 12 months. HS was evaluated using the EQ-5D questionnaire at 6 weeks, 6 months, and 12 months. Multiple regression analysis and hierarchical linear models were applied to identify influencing factors in ADL and HS. RESULTS: The BI was 95 pre-fracture, 75 at 6 weeks (p < 0.001), 80 at 6 months (p = 0.178), and 80 at 12 months (p = 0.149). The IADL was 6 pre-fracture, 3 at 6 weeks (p < 0.001), 4 at 6 months (p = 0.004), and 4 at 12 months (p = 0.711). The EQ-5D index was 0.70 at 6 weeks, 0.788 at 6 months (p = 0.158), and 0.788 at 12 months (p = 0.798). Significant influencing factors in the multiple regression analysis were pre-fracture nursing care level for all scores; pre-fracture mobility for BI; and pre-fracture IADL, ASA score, and age for IADL. Significant influencing factors in the hierarchical linear model were pre-fracture nursing care level for all scores; pre-fracture IADL, ASA score, age, and time for IADL; and pre-fracture mobility, sex, and time for the EQ-5D. CONCLUSION: Our results confirm that FFP lead to a significant, long-lasting deterioration in ADL and HS, comparable with hip fractures.

Quantitative myocardial perfusion SPECT/CT for the assessment of myocardial tracer uptake in patients with three-vessel coronary artery disease: Initial experiences and results.

BACKGROUND: To evaluate quantitative myocardial perfusion SPECT/CT datasets for routine clinical reporting and the assessment of myocardial tracer uptake in patients with severe TVCAD. METHODS: MPS scans were reconstructed as quantitative SPECT datasets using CTs from internal (SPECT/CT, Q_INT) and external (PET/CT, Q_EXT) sources for attenuation correction. TPD was calculated and compared to the TPD from non-quantitative SPECT datasets of the same patients. SUVmax, SUVpeak, and SUVmean were compared between Q_INT and Q_EXT SPECT datasets. Global SUVmax and SUVpeak were compared between patients with and without TVCAD. RESULTS: Quantitative reconstruction was feasible. TPD showed an excellent correlation between quantitative and non-quantitative SPECT datasets. SUVmax, SUVpeak, and SUVmean showed an excellent correlation between Q_INT and Q_EXT SPECT datasets, though mean SUVmean differed significantly between the two groups. Global SUVmax and SUVpeak were significantly reduced in patients with TVCAD. CONCLUSIONS: Absolute quantification of myocardial tracer uptake is feasible. The method seems to be robust and principally suitable for routine clinical reporting. Quantitative SPECT might become a valuable tool for the assessment of severe coronary artery disease in a setting of balanced ischemia, where potentially life-threatening conditions might otherwise go undetected.

Is cement-augmented sacroiliac screw fixation with partially threaded screws superior to that with fully threaded screws concerning compression and pull-out force in fragility fractures of the sacrum? - a biomechanical analysis.

BACKGROUND: Providing a stable osteosynthesis in fragility fractures of the pelvis can be challenging. Cement augmentation increases screw fixation in osteoporotic bone. Generating interfragmentary compression by using a lag screw also improves the stability. However, it is not known if interfragmentary compression can be achieved in osteoporotic sacral bone by cement augmentation of lag screws. The purpose of this study was to compare cement-augmented sacroiliac screw osteosynthesis using partially versus fully threaded screws in osteoporotic hemipelvises concerning compression of fracture gap and pull-out force. METHODS: Nine fresh-frozen human cadaveric pelvises with osteoporosis were used. In all specimens, one side was treated with an augmented fully threaded screw (group A), and the other side with an augmented partially threaded screw (group B) after generating a vertical osteotomy on both sides of each sacrum. Afterwards, first a compression test with fracture gap measurement after tightening of the screws was performed, followed by an axial pull-out test measuring the maximum pull-out force of the screws. RESULTS: The fracture gap was significantly wider in group A (mean: 1.90 mm; SD: 1.64) than in group B (mean: 0.91 mm; SD: 1.03; p = 0.028). Pull-out force was higher in group A (mean: 1696 N; SD: 1452) than in group B (mean: 1616 N; SD: 824), but this difference was not statistically significant (p = 0.767). CONCLUSIONS: Cement augmentation of partially threaded screws in sacroiliac screw fixation allows narrowing of the fracture gap even in osteoporotic bone, while resistance against pull-out force is not significantly lower in partially threaded screws compared to fully threaded screws.

Which factors influence treatment decision in fragility fractures of the pelvis? - results of a prospective study.

BACKGROUND: The aim of the present study was to describe specific characteristics of patients suffering from pelvic fragility fractures and evaluate factors that might influence treatment decisions which may optimize treatment pathways and patient mobility in the future. METHODS: A prospective study with patients suffering from fractures of the pelvis and aged 60 years or above was performed between 2012 and 2016. Data acquisition took place at admission, every day during hospitalization and at discharge. RESULTS: One hundred thirty-four patients (mean age of 79.93 (± 7.67) years), predominantly female (84%), were included. Eighty-six patients were treated non-operatively. Forty-eight patients underwent a surgical procedure. The main fracture types were B2 fractures (52.24%) and FFP IIb fractures (39.55%). At the time of discharge, pain level (NRS) could be significantly reduced (p <  0.001). Patients who underwent a surgical procedure had a significantly higher pain level on day three and four compared to the non-operative group (p = 0.032 and p = 0.023, respectively). Significant differences were found in the mobility level: patients treated operatively on day four or later were not able to stand or walk on day three as compared to non-operatively treated patients. Regarding B2 fractures, a significantly higher mobility level difference between time of admission and discharge was found in patients treated with a surgical procedure compared to patients treated non-operatively (p = 0.035). CONCLUSIONS: Fracture type, mobility level and pain level influence the decision to proceed with surgical treatment. Especially patients suffering from B2 fractures benefitted in terms of mobility level at discharge when treated operatively. LEVEL OF EVIDENCE: II.

[Female doctors in orthopedics and trauma surgery in Germany: a current status quo]. / Ärztinnen in der Orthopädie und Unfallchirurgie in Deutschland: ein aktueller Status quo.

BACKGROUND: Gender-specific differences in the workplace in general and in the field of orthopedics and trauma surgery in particular are still clearly identifiable, and are becoming more and more pronounced in the social consciousness. OBJECTIVE: Analysis of the gender-specific development in the specialist field of orthopedics and trauma surgery in Germany over the past 15 years and a survey of the status quo. METHODS: Assessment of the development of female graduates in the study of human medicine, the proportion of women in accredited and clinical care and the gender-specific acquisition of an additional orthopedic/trauma surgical title. Evaluation of gender-specific numbers of members or participants in the relevant professional associations and the largest German conferences on orthopedics and trauma surgery, as well as the habilitation figures in the field of orthopedics. RESULTS AND DISCUSSION: The proportion of female doctors in various fields of orthopedics and trauma surgery in the clinic and in science is increasing. There is still a clear discrepancy in leading positions in clinics, in the acquisition of an additional title, and on the boards of professional associations. In some fields, such as pediatric and hand/foot/ankle surgery, the proportion of women is higher than in other sub-areas of orthopedics and trauma surgery.

Influence of curricular reforms in mental health nursing education between 1969 and 2014. / Influência das reformas curriculares no ensino de saúde mental em enfermagem: 1969 a 2014.

Objective To analyze the influence of curricular changes in mental health nursing education at the Federal University of Santa Catarina. Method Qualitative research, exploratory and descriptive. Data were collected in official ordinances in the Pedagogical Projects of the Nursing Course and in the Teaching Plans in the period from 1969 to 2014. The data collection was carried out between the months of March and December 2015. We used a spreadsheet to organize the data and they were analyzed according to the technique of documentary analysis. Results Trends in curricular changes were highlighted after the Curricular and Psychiatric Reforms. The most significant changes occurred since 2004 with the National Curriculum Guidelines and Law 10.2016. Conclusion It was found that the curricular changes occurred from induction and from outside the educational institution policies. The influences resulted in changes in the name of courses, course offerings and course objectives, and integration between courses and practical settings, among others.

Tennis Injuries Among German League Players: Investigating Patterns and Epidemiology of Acute and Chronic Injuries.

Purpose: While injuries among elite tennis athletes are extensively documented, a notable research gap exists regarding tennis injuries among club-level players. This study examines tennis injuries in German league players, with a particular emphasis on the impact of racquet properties and court surfaces, distinguishing between chronic and acute injuries. Patients and Methods: Retrospectively analyzing data from 600 tennis players over a 1.5-year period, a standardized questionnaire covered anthropometrics, injury characteristics, equipment usage, and court surface conditions. Results: The study identified 1012 tennis-related injuries, averaging 1.7 per player. Acute injuries predominantly affected the lower extremity (56%), with ankle injuries being the most prevalent, and ligaments were the most commonly affected structures (36.4%). Chronic complaints (reported by 364 athletes) focused on the upper extremity (63.2%), primarily tendon injuries (56.8%). Racket properties exhibited no significant impact on chronic upper extremity injuries. Conclusion: This study highlights a high incidence of acute lower extremity injuries, especially ankle ligament injuries, among German league tennis players. It offers crucial insights for devising targeted injury prevention strategies applicable to amateur, semi-professional, and professional tennis players, despite finding no significant link between racquet material and chronic upper extremity injuries.

An International Study of Factors Affecting Variability of Dosimetry Calculations, Part 3: Contribution from Calculating Absorbed Dose from Time-Integrated Activity.

Image-based dosimetry-guided radiopharmaceutical therapy has the potential to personalize treatment by limiting toxicity to organs at risk and maximizing the therapeutic effect. The 177Lu dosimetry challenge of the Society of Nuclear Medicine and Molecular Imaging consisted of 5 tasks assessing the variability in the dosimetry workflow. The fifth task investigated the variability associated with the last step, dose conversion, of the dosimetry workflow on which this study is based. Methods: Reference variability was assessed by 2 medical physicists using different software, methods, and all possible combinations of input segmentation formats and time points as provided in the challenge. General descriptive statistics for absorbed dose values from the global submissions from participants were calculated, and variability was measured using the quartile coefficient of dispersion. Results: For the liver, which included lesions with high uptake, variabilities of up to 36% were found. The baseline analysis showed a variability of 29% in absorbed dose results for the liver from datasets where lesions included and excluded were grouped, indicating that variation in how lesions in normal liver were treated was a significant source of variability. For other organs and lesions, variability was within 7%, independently of software used except for the local deposition method. Conclusion: The choice of dosimetry method or software had a small contribution to the overall variability of dose estimates.

DosePatch: physics-inspired cropping layout for patch-based Monte Carlo simulations to provide fast and accurate internal dosimetry.

BACKGROUND: Dosimetry-based personalized therapy was shown to have clinical benefits e.g. in liver selective internal radiation therapy (SIRT). Yet, there is no consensus about its introduction into clinical practice, mainly as Monte Carlo simulations (gold standard for dosimetry) involve massive computation time. We addressed the problem of computation time and tested a patch-based approach for Monte Carlo simulations for internal dosimetry to improve parallelization. We introduce a physics-inspired cropping layout for patch-based MC dosimetry, and compare it to cropping layouts of the literature as well as dosimetry using organ-S-values, and dose kernels, taking whole-body Monte Carlo simulations as ground truth. This was evaluated in five patients receiving Yttrium-90 liver SIRT. RESULTS: The patch-based Monte Carlo approach yielded the closest results to the ground truth, making it a valid alternative to the conventional approach. Our physics-inspired cropping layout and mosaicking scheme yielded a voxel-wise error of < 2% compared to whole-body Monte Carlo in soft tissue, while requiring only ≈  10% of the time. CONCLUSIONS: This work demonstrates the feasibility and accuracy of physics-inspired cropping layouts for patch-based Monte Carlo simulations.

Impact of the Reference Multiple-Time-Point Dosimetry Protocol on the Validity of Single-Time-Point Dosimetry for [177Lu]Lu-PSMA-I&T Therapy.

Internal dosimetry supports safe and effective patient management during radionuclide therapy. Yet, it is associated with high clinical workload, costs, and patient burden, as patient scans at multiple time points (MTPs) must be acquired. Dosimetry based on imaging at a single time point (STP) has continuously gained popularity. However, MTP protocols, used as a reference to judge the validity of STP dosimetry, differ depending on local requirements and deviate from the unknown patient-specific ground truth pharmacokinetics. The aim of this study was to compare the error and optimum time point for different STP approaches using different reference MTP protocols. Methods: Whole-body SPECT/CT scans of 7 patients (7.4-8.9 GBq of [177Lu]Lu-PSMA-I&T) were scheduled at 24, 48, 72, and 168 h after injection. Sixty lesions, 14 kidneys, and 10 submandibular glands were delineated in the SPECT/CT data. Two curve models, that is, a mono- and a biexponential model, were fitted to the MTP data, in accordance with goodness-of-fit analysis (coefficients of variation, sum of squared errors). Three population-based STP approaches were compared: one method published by Hänscheid et al., one by Jackson et al., and one using population-based effective half-lives in the mono- or biexponential curve models. Percentage differences between STP and MTP dosimetry were evaluated. Results: Goodness-of-fit parameters show that a monoexponential function and a biexponential function with shared population-based parameters and physical tail are reasonable reference models. When comparing both reference models, we observed maximum differences of -44%, -19%, and -28% in the estimated absorbed doses for lesions, kidneys, and salivary glands, respectively. STP dosimetry with an average deviation of less than 10% from MTP dosimetry may be feasible; however, this deviation and the optimum imaging time point showed a dependence on the chosen reference protocol. Conclusion: STP dosimetry for [177Lu]Lu-PSMA therapy is promising to boost the integration of dosimetry into clinical routine. According to our patient cohort, 48 h after injection may be regarded as a compromise for STP dosimetry for lesions and at-risk organs. The results from this analysis show that a common gold standard for dosimetry is desirable to allow for reliable and comparable STP dosimetry.

Long-Term Nephrotoxicity of 177Lu-PSMA Radioligand Therapy.

ß-emitting 177Lu targeting prostate-specific membrane antigen (PSMA) is an approved treatment option for metastatic castration-resistant prostate cancer. Data on its long-term nephrotoxicity are sparse. This study aimed to retrospectively evaluate post-177Lu-PSMA estimated glomerular filtration rate (eGFR) dynamics for at least 12 mo in a cohort of metastatic castration-resistant prostate cancer patients. Methods: The institutional databases of 3 German tertiary referral centers identified 106 patients who underwent at least 4 cycles of 177Lu-PSMA and had at least 12 mo of eGFR follow-up data. eGFR (by the Chronic Kidney Disease Epidemiology Collaboration formula) at 3, 6, and 12 mo after 177Lu-PSMA radioligand therapy was estimated using monoexponentially fitted curves through available eGFR data. eGFR changes were grouped (≥15%-<30%, moderate; ≥30%-<40%, severe; and ≥40%, very severe). Associations between eGFR changes (%) and nephrotoxic risk factors, prior treatment lines, and number of 177Lu-PSMA cycles were analyzed using multivariable linear regression. Results: At least moderate eGFR decreases were present in 45% (48/106) of patients; of those, nearly half (23/48) had a severe or very severe eGFR decrease. A higher number of risk factors at baseline (-4.51, P = 0.03) was associated with a greater eGFR decrease. Limitations of the study were the retrospective design, lack of a control group, and limited number of patients with a follow-up longer than 1 y. Conclusion: A considerable proportion of patients may experience moderate or severe decreases in eGFR 1 y from initiation of 177Lu-PSMA. A higher number of risk factors at baseline seems to aggravate loss of renal function. Further prospective trials are warranted to estimate the nephrotoxic potential of 177Lu-PSMA.

Theranostic digital twins: Concept, framework and roadmap towards personalized radiopharmaceutical therapies.

Radiopharmaceutical therapy (RPT) is a rapidly developing field of nuclear medicine, with several RPTs already well established in the treatment of several different types of cancers. However, the current approaches to RPTs often follow a somewhat inflexible "one size fits all" paradigm, where patients are administered the same amount of radioactivity per cycle regardless of their individual characteristics and features. This approach fails to consider inter-patient variations in radiopharmacokinetics, radiation biology, and immunological factors, which can significantly impact treatment outcomes. To address this limitation, we propose the development of theranostic digital twins (TDTs) to personalize RPTs based on actual patient data. Our proposed roadmap outlines the steps needed to create and refine TDTs that can optimize radiation dose to tumors while minimizing toxicity to organs at risk. The TDT models incorporate physiologically-based radiopharmacokinetic (PBRPK) models, which are additionally linked to a radiobiological optimizer and an immunological modulator, taking into account factors that influence RPT response. By using TDT models, we envisage the ability to perform virtual clinical trials, selecting therapies towards improved treatment outcomes while minimizing risks associated with secondary effects. This framework could empower practitioners to ultimately develop tailored RPT solutions for subgroups and individual patients, thus improving the precision, accuracy, and efficacy of treatments while minimizing risks to patients. By incorporating TDT models into RPTs, we can pave the way for a new era of precision medicine in cancer treatment.

Therapy of a Chronically Infected Total Femur Prothesis in a 40-year-old Patient. / Therapie einer chronischen Infektion einer totalen Femurendoprothese bei einem 40-jährigen Patienten.

We report a case of a patient who was treated in 1999 at the age of 19 years with a proximal femur replacement due to Ewing sarcoma. After several infection-associated exchange procedures, the patient presented with a fistula and chronic infection of a total femur prosthesis in August 2019 at the age of 40 years. Interdisciplinary treatment with a 3-stage exchange procedure and implantation of a silver-coated total femur prosthesis was successfully performed and hip disarticulation could be avoided. After a follow-up of 2 years, the patient showed uneventful wound healing and full weight bearing without crutches.

Cemented Sacroiliac Screw Fixation versus Conservative Therapy in Fragility Fractures of the Posterior Pelvic Ring: A Matched-Pair Analysis of a Prospective Observational Study.

The aim of this study was to compare the outcome of cemented sacroiliac screw fixation to that of conservative treatment in nondisplaced fragility fractures of the sacrum during a 12-month follow-up. Therefore, matched-pair analysis including 40 patients from a previously performed prospective observational study was conducted. Pain was assessed using the visual analogue scale (VAS), functional capabilities and mobility were assessed using the Barthel index, and health-related quality of life (HRQL) was assessed using the EQ-5D questionnaire at 6 weeks, 6 months, and 12 months after the fracture, respectively. No significant differences between the two groups were seen regarding pain. In the operative group, a significantly improved Barthel index was observed after 6 months. A significantly higher HRQL was identified after 6 weeks in the operative group. Their mobility was comparable between the two groups before the fracture; after 6 weeks, mobility was significantly improved in the operative group. After 12 months, no significant differences were found regarding the functional outcome, HRQL or mobility. The 1-year mortality rate was 25% in the conservative group versus 5% in the operative group (not statistically significant). The present study revealed favorable short-term outcomes concerning the functional outcome, HRQL and mobility after sacroiliac screw fixation. After 12 months, the outcomes were similar to those of the patients managed conservatively.

On the Use of Artificial Intelligence for Dosimetry of Radiopharmaceutical Therapies.

Routine clinical dosimetry along with radiopharmaceutical therapies is key for future treatment personalization. However, dosimetry is considered complex and time-consuming with various challenges amongst the required steps within the dosimetry workflow. The general workflow for image-based dosimetry consists of quantitative imaging, the segmentation of organs and tumors, fitting of the time-activity-curves, and the conversion to absorbed dose. This work reviews the potential and advantages of the use of artificial intelligence to improve speed and accuracy of every single step of the dosimetry workflow.

An International Study of Factors Affecting Variability of Dosimetry Calculations, Part 2: Overall Variabilities in Absorbed Dose.

Dosimetry for personalized radiopharmaceutical therapy has gained considerable attention. Many methods, tools, and workflows have been developed to estimate absorbed dose (AD). However, standardization is still required to reduce variability of AD estimates across centers. One effort for standardization is the Society of Nuclear Medicine and Molecular Imaging 177Lu Dosimetry Challenge, which comprised 5 tasks (T1-T5) designed to assess dose estimate variability associated with the imaging protocol (T1 vs. T2 vs. T3), segmentation (T1 vs. T4), time integration (T4 vs. T5), and dose calculation (T5) steps of the dosimetry workflow. The aim of this work was to assess the overall variability in AD calculations for the different tasks. Methods: Anonymized datasets consisting of serial planar and quantitative SPECT/CT scans, organ and lesion contours, and time-integrated activity maps of 2 patients treated with 177Lu-DOTATATE were made available globally for participants to perform dosimetry calculations and submit their results in standardized submission spreadsheets. The data were carefully curated for formal mistakes and methodologic errors. General descriptive statistics for ADs were calculated, and statistical analysis was performed to compare the results of different tasks. Variability in ADs was measured using the quartile coefficient of dispersion. Results: ADs to organs estimated from planar imaging protocols (T2) were lower by about 60% than those from pure SPECT/CT (T1), and the differences were statistically significant. Importantly, the average differences in dose estimates when at least 1 SPECT/CT acquisition was available (T1, T3, T4, T5) were within ±10%, and the differences with respect to T1 were not statistically significant for most organs and lesions. When serial SPECT/CT images were used, the quartile coefficients of dispersion of ADs for organs and lesions were on average less than 20% and 26%, respectively, for T1; 20% and 18%, respectively, for T4 (segmentations provided); and 10% and 5%, respectively, for T5 (segmentation and time-integrated activity images provided). Conclusion: Variability in ADs was reduced as segmentation and time-integration data were provided to participants. Our results suggest that SPECT/CT-based imaging protocols generate more consistent and less variable results than planar imaging methods. Effort at standardizing segmentation and fitting should be made, as this may substantially reduce variability in ADs.