RECIP 1.0 Predicts Progression-Free Survival After [177Lu]Lu-PSMA Radiopharmaceutical Therapy in Patients with Metastatic Castration-Resistant Prostate Cancer.

Response Evaluation Criteria in Prostate-Specific Membrane Antigen Imaging (RECIP) 1.0 is an evidence-based framework to evaluate therapeutic efficacy in metastatic prostate cancer using prostate-specific membrane antigen (PSMA) PET/CT. This study aimed to evaluate the associations of interim PSMA PET/CT by RECIP 1.0 with short-term outcome after radiopharmaceutical treatment. Methods: This multicenter retrospective study included patients with metastatic castration-resistant prostate cancer who underwent [177Lu]Lu-PSMA radiopharmaceutical therapy at 3 academic centers and received PSMA PET/CT at baseline and at 12 wk. Pairs of PSMA PET/CT images were assessed by 5 readers for visual RECIP 1.0. The primary outcome was the association of RECIP with prostate-specific antigen progression-free survival (PSA-PFS) by Kaplan-Meier analysis. Results: In total, 124 of 287 screened patients met the inclusion criteria, with 0 (0%), 29 (23%), 54 (44%), and 41 (33%) of those 124 patients having complete response, partial response, stable disease, or progressive disease (PD) by visual RECIP 1.0, respectively. Patients with visual RECIP PD had a significantly shorter PSA-PFS than those with RECIP stable disease or with RECIP partial response (2.6 vs. 6.4 vs. 8.4 mo; P < 0.001). The median PSA-PFS among patients with RECIP PD versus those with non-RECIP PD was 2.6 versus 7.2 mo (hazard ratio, 13.0; 95% CI, 7.0-24.1; P < 0.001). Conclusion: PSMA PET/CT by RECIP 1.0 after 2 cycles of [177Lu]Lu-PSMA is prognostic for PSA-PFS. PSMA PET/CT by RECIP 1.0 may be used in earlier stages of prostate cancer to evaluate drug efficacy and to predict progression-free survival.

Prostate-specific Membrane Antigen Positron Emission Tomography-detected Disease Extent and Overall Survival of Patients with High-risk Nonmetastatic Castration-resistant Prostate Cancer: An International Multicenter Retrospective Study.

Previously, we demonstrated that prostate-specific membrane antigen positron emission tomography (PSMA-PET) revealed distant metastases in 109/200 patients (39% distant nodes, 24% bone, and 6% visceral organ) with nonmetastatic castration-resistant prostate cancer (nmCRPC) and high-risk features (International Society of Urological Pathology score ≥4 and/or prostate-specific antigen doubling time ≤10 mo) without metastases by conventional imaging. However, the impact of disease extent determined by PSMA-PET on patient outcomes is unknown. We followed these 200 patients for a median of 43 mo after PSMA-PET and retrospectively assessed the association between patient characteristics, PSMA-PET findings, treatment management, and outcomes using a Kaplan-Meier model and Cox multivariable regressions. Among assessed disease characteristics, polymetastatic disease (five or more distant lesions on PET) was independently associated with shorter overall survival (OS; median 61 mo vs not reached; hazard ratio [95% confidence interval], 1.81 [1.00-3.27]; p = 0.050) and time to new metastases (median 38 vs 60 mo; 1.80 [1.10-2.96]; p = 0.019), and initial pN1 status with shorter OS (55 mo vs not reached; 1.94 [1.12-3.37]; p = 0.019). Following PSMA-PET, locoregional salvage therapies were used most commonly in no/local disease (58%), and androgen receptor signaling inhibitors were used in distant metastatic disease (51%). PSMA-PET provides additional risk stratification for patients with nmCRPC. Polymetastatic disease (five or more distant lesions) is associated with worse outcomes. PATIENT SUMMARY: A novel sensitive imaging technology, called prostate-specific membrane antigen positron emission tomography (PSMA-PET), allows doctors to detect the spread of prostate cancer, known as distant metastases, earlier and more accurately than in the past. In our study, PSMA-PET detected none to many metastases in patients who were considered free of distant metastasis by conventional imaging. These findings predicted outcomes and were used to select appropriate treatment.

Neoadjuvant Radiochemotherapy Alters the Immune and Metabolic Microenvironment in Oral Cancer-Analyses of CD68, CD163, TGF-ß1, GLUT-1 and HIF-1α Expressions.

BACKGROUND: The first-line treatment of oral squamous cell carcinoma (OSCC) involves surgical tumor resection, followed by adjuvant radio(chemo)therapy (R(C)T) in advanced cases. Neoadjuvant radio- and/or chemotherapy has failed to show improved survival in OSCC. Recently, neoadjuvant immunotherapy has shown promising therapeutic efficacy in phase 2 trials. In this context, the addition of radio- and chemotherapy is being reconsidered. Therefore, a better understanding of the tumor-biologic effects of neoadjuvant RCT would be beneficial. The current study was conducted on a retrospective cohort of patients who received neoadjuvant RCT for the treatment of oral cancer. The aim of the study was to evaluate the influence of neoadjuvant RCT on the immunological tumor microenvironment (TME) and hypoxic and glucose metabolisms. METHODS: A cohort of 45 OSSC tissue samples from patients were analyzed before and after RCT (total 50.4 Gy; 1.8 Gy 5× weekly; Cisplatin + 5-Fluorouracil). Immunohistochemistry for CD68, CD163, TGF-ß, GLUT-1 and HIF-1α was performed using tissue microarrays and automated cell counting. Differences in expression before and after RCT and associations with histomorphological parameters (T-status, N-status) were assessed using the Mann-Whitney U test. RESULTS: Tumor resection specimens after neoadjuvant RCT showed a significant decrease in CD68 infiltration and a significant increase in CD163 cell density. The CD68/CD163 ratio was significantly lower after RCT, indicating a shift toward M2 polarization. The GLUT-1 and HIF-1α expressions were significantly lower after RCT. Larger tumors (T3/T4) showed a lower GLUT-1 expression. Other biomarkers were not associated with the T- and N-status. CONCLUSIONS: Neoadjuvant RCT with 50.4 Gy induced a shift toward the M2 polarization of macrophages in the TME. This change in immune composition is not favorable and may be prognostically negative and counteract immunotherapeutic approaches. In addition, the decreased expressions in GLUT-1 and HIF-1α indicate reductions in the glucose metabolism and hypoxic energy metabolism in response to "high dose" neoadjuvant RCT, which may be therapeutically desirable.

Efficacy of a digital lifestyle intervention on health-related QUAlity of life in non-small cell LUng CAncer survivors following inpatient rehabilitation: protocol of the QUALUCA Swiss multicentre randomised controlled trial.

INTRODUCTION: Non-small cell lung cancer (NSCLC) survivors suffer from impaired physical and psychological functioning and reduced health-related quality of life (HRQoL) that persist after active treatment ends. Sustaining rehabilitation benefits, promoting a healthy lifestyle and facilitating self-management at home require a multifaceted aftercare programme. We aim to investigate the effect of a 12-week digital lifestyle intervention on HRQoL and lifestyle-related outcomes in NSCLC survivors after completion of inpatient rehabilitation. METHODS AND ANALYSIS: QUAlity of life in LUng CAncer Survivors (QUALUCA) is a multicentre randomised controlled trial that follows a hybrid type 1 design. We randomly allocate participants in a 1:1 ratio to the intervention group (digital lifestyle intervention) or the control group (standard care) using block randomisation stratified by tumour stage and study site. Four accredited Swiss inpatient rehabilitation centres recruit participants. Key inclusion criteria are a diagnosis of NSCLC, an estimated life expectancy of ≥6 months and access to a smartphone or tablet. The 12-week intervention comprises physical activity, nutrition and breathing/relaxation, delivered through a mobile application (app). The primary outcome is the change in HRQoL from baseline (1 week after rehabilitation) to follow-up (3 months after baseline), assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Secondary outcomes include body mass index, self-reported physical activity, exercise capacity, risk of low protein intake, appetite, psychological distress, cancer-related fatigue, enablement and self-rated health. Explanatory outcomes in the intervention group include app usability, acceptability, appropriateness, and feasibility of the intervention, experiences and satisfaction with the intervention, and app usage data. We aim to enrol 88 participants. For the main statistical analysis, we will use analysis of covariance, adjusted for baseline measures, stratification variables, age and sex. ETHICS AND DISSEMINATION: The Ethics Committees of the Canton of Zurich (lead), the Canton of Bern and Northwest and Central Switzerland approved the study (2023-00245). We will disseminate study results to researchers, health professionals, study participants and relevant organisations, and through publications in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05819346.

Nontargeted Volatile Metabolite Screening and Microbial Contamination Detection in Fermentation Processes by Headspace GC-IMS.

Gas chromatography combined with ion mobility spectrometry (GC-IMS) is a powerful separation and detection technique for volatile organic compounds (VOC). This combination is characterized by exceptionally low detection limits in the low ppbv range, high 2-dimensional selectivity, and robust operation. These qualities make it an ideal tool for nontarget screening approaches. Fermentation broths contain a substantial number of VOC, either from the medium or produced by microbial metabolism, that are currently not regularly measured for process monitoring. In this study, Escherichia coli, Saccharomyces cerevisiae, Levilactobacillus brevis, and Pseudomonas fluorescens were exemplarily used as model organisms and cultivated, and the headspace was analyzed by GC-IMS. Additionally, mixed cultures for every combination of two of the microorganisms were also characterized. Multivariate data analysis of the GC-IMS data revealed that it is possible to differentiate between the microorganisms using PLS-DA with a prediction accuracy of 0.92. The mixed cultures could be separated from the pure cultures with accuracies between 0.87 and 1.00 depending on the organism. GC-IMS data correlate with the optical density and can be used to follow and model growth curves. The root mean squared errors ranged between 10 and 20% of the maximum value, depending on the organism. Peak identification with reference compounds did not reveal specific marker compounds, rather the pattern was found to be responsible for the model performance.

Is blinding in studies of manual soft tissue mobilisation of the back possible? A feasibility randomised controlled trial with Swiss graduate students.

STUDY DESIGN: Single-centre, two-parallel group, methodological randomised controlled trial to assess blinding feasibility. BACKGROUND: Trials of manual therapy interventions of the back face methodological challenges regarding blinding feasibility and success. We assessed the feasibility of blinding an active manual soft tissue mobilisation and control intervention of the back. We also assessed whether blinding is feasible among outcome assessors and explored factors influencing perceptions about intervention assignment. METHODS: On 7-8 November 2022, 24 participants were randomly allocated (1:1 ratio) to active or control manual interventions of the back. The active group (n = 11) received soft tissue mobilisation of the lumbar spine. The control group (n = 13) received light touch over the thoracic region with deep breathing exercises. The primary outcome was blinding of participants immediately after a one-time intervention session, as measured by the Bang blinding index (Bang BI). Bang BI ranges from -1 (complete opposite perceptions of intervention received) to 1 (complete correct perceptions), with 0 indicating 'random guessing'-balanced 'active' and 'control' perceptions within an intervention arm. Secondary outcomes included blinding of outcome assessors and factors influencing perceptions about intervention assignment among both participants and outcome assessors, explored via thematic analysis. RESULTS: 24 participants were analysed following an intention-to-treat approach. 55% of participants in the active manual soft tissue mobilisation group correctly perceived their group assignment beyond chance immediately after intervention (Bang BI: 0.55 [95% confidence interval (CI), 0.25 to 0.84]), and 8% did so in the control group (0.08 [95% CI, -0.37 to 0.53]). Bang BIs in outcome assessors were 0.09 (-0.12 to 0.30) and -0.10 (-0.29 to 0.08) for active and control participants, respectively. Participants and outcome assessors reported varying factors related to their perceptions about intervention assignment. CONCLUSIONS: Blinding of participants allocated to an active soft tissue mobilisation of the back was not feasible in this methodological trial, whereas blinding of participants allocated to the control intervention and outcome assessors was adequate. Findings are limited due to imprecision and suboptimal generalisability to clinical settings. Careful thinking and consideration of blinding in manual therapy trials is warranted and needed. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05822947 (retrospectively registered).

Biodistribution and radiation dosimetry of 124I-mIBG in adult patients with neural crest tumours and extrapolation to paediatric models.

AIM: Positron emission tomography (PET) using 124I-mIBG has been established for imaging and pretherapeutic dosimetry. Here, we report the first systematic analysis of the biodistribution and radiation dosimetry of 124I-mIBG in patients with neural crest tumours and project the results to paediatric patient models. METHODS: Adult patients with neural crest tumours who underwent sequential 124I-mIBG PET were included in this retrospective single-center analysis. PET data were acquired 4, 24, 48, and/or 120 h after administration of a mean of 43 MBq 124I-mIBG. Whole-body counting and blood sampling were performed at 2, 4, 24, 48 and 120 h after administration. Absorbed organ dose and effective dose coefficients were estimated in OLINDA/EXM 2.2 according to the MIRD formalism. Extrapolation to paediatric models was performed based on mass-fraction scaling of the organ-specific residence times. Biodistribution data for adults were also projected to 123I-mIBG and 131I-mIBG. RESULTS: Twenty-one patients (11 females, 10 males) were evaluated. For adults, the organs exposed to the highest dose per unit administered activity were urinary bladder (1.54 ± 0.40 mGy/MBq), salivary glands (0.77 ± 0.28 mGy/MBq) and liver (0.65 ± 0.22 mGy/MBq). Mean effective dose coefficient for adults was 0.25 ± 0.04 mSv/MBq (male: 0.24 ± 0.03 mSv/MBq, female: 0.26 ± 0.06 mSv/MBq), and increased gradually to 0.29, 0.44, 0.69, 1.21, and 2.94 mSv/MBq for the 15-, 10-, 5-, 1-years-old, and newborn paediatric reference patients. Projected mean effective dose coefficients for 123I-mIBG and 131I-mIBG for adults were 0.014 ± 0.002 mSv/MBq and 0.18 ± 0.04 mSv/MBq, respectively. CONCLUSION: PET-based derived radiation dosimetry data for 124I-mIBG from this study agreed well with historical projected data from ICRP 53. The effective dose coefficients presented here may aid in guidance for establishing weight-based activity administration protocols.

Airway management in a two-year-old child with a tongue tumor using video laryngoscope-assisted flexible bronchoscopic nasotracheal intubation (hybrid technique).

Airway management in children can be challenging. A hybrid technique using a video laryngoscope-assisted flexible bronchoscopic nasotracheal intubation allowed a successful airway management in a two-year-old child with a large tongue tumor.

Changes in tumor-to-blood ratio as a prognostic marker for progression-free survival and overall survival in neuroendocrine tumor patients undergoing PRRT.

BACKGROUND: Historically, patient selection for peptide receptor radionuclide therapy (PRRT) has been performed by virtue of somatostatin receptor scintigraphy (SRS). In recent years, somatostatin receptor positron emission tomography (SSTR-PET) has gradually replaced SRS because of its improved diagnostic capacity, creating an unmet need for SSTR-PET-based selection criteria for PRRT. Tumor-to-blood ratio (TBR) measurements have shown high correlation with the net influx rate Ki, reflecting the tumor somatostatin receptor expression, to a higher degree than standardized uptake value (SUV) measurements. TBR may therefore predict treatment response to PRRT. In addition, changes in semiquantitative SSTR-PET parameters have been shown to predate morphological changes, making them a suitable metric for response assessment. METHODS: The institutional database of the Department of Nuclear Medicine (University Hospital Essen) was searched for NET patients undergoing ≥ 2 PRRT cycles with available baseline and follow-up SSTR-PET. Two blinded independent readers reported the occurrence of new lesions quantified tumor uptake of up to nine lesions per patient using SUV and TBR. The association between baseline TBR and changes in uptake/occurrence of new lesions with progression-free survival (PFS) and overall survival (OS) was tested by use of a Cox regression model and log-rank test. RESULTS: Patients with baseline TBR in the 1st quartile had a shorter PFS (14.4 months) than those in the 3rd (23.7 months; p = 0.03) and 4th (24.1 months; p = 0.02) quartile. Similarly, these patients had significantly shorter OS (32.5 months) than those with baseline TBR in the 2nd (41.8 months; p = 0.03), 3rd (69.2 months; p < 0.01), and 4th (42.7 months; p = 0.03) quartile. Baseline to follow-up increases in TBR were independently associated with shorter PFS when accounting for prognostic markers, e.g., RECIST response (hazard ratio = 2.91 [95%CI = 1.54-5.50]; p = 0.01). This was confirmed with regard to OS (hazard ratio = 1.64 [95%CI = 1.03-2.62]; p = 0.04). Changes in SUVmean were not associated with PFS or OS. CONCLUSIONS: Baseline TBR as well as changes in TBR were significantly associated with PFS and OS and may improve patient selection and morphological response assessment. Future trials need to assess the role of TBR for therapy monitoring also during PRRT and prospectively explore TBR as a predictive marker for patient selection.

Prevalence of carotid artery calcification detected by different dental imaging techniques and their relationship with cardiovascular risk factors, age and gender.

BACKGROUND: Atherosclerosis and its secondary diseases display a major threat to patient's health. Sequelae, like carotid artery calcification (CAC), usually develop over decades and remain asymptomatic for a long time, making preventive measures to reduce mortality and morbidity extremely important. Through panoramic radiography (PR) and cone beam computed tomography (CBCT), dentists may have helpful tools in aiding the holistic care of patients. In this context, the correlation of atherosclerotic risk factors and CAC development have not yet been sufficiently investigated. Thus, the aim of this observational radiological study was to evaluate the diagnostic value of PR compared with CBCT for the detection of CAC in patients older than 60 years. The radiological findings were correlated with gender, age, and cardiac risk factors. METHODS: PRs and CBCTs of N = 607 patients were used for the qualitative analysis and compared. Basic patient information such as age, gender, body mass index (BMI), smoking history as well as patient's detailed medical history, including heart disease and cardiovascular risk factors such as hypercholesterolemia, arterial hypertension and diabetes mellitus type II were documented and their relation to CAC provided by radiological data was estimated in the form of odds ratios (OR), which were calculated using logistic regression models. Proportions of CAC in different risk groups were compared using Fisher's exact test, the significance level was set to α ≤ 0.05. The interrater reliability of two physicians was estimated using Cohen's kappa. RESULTS: With an accuracy of 90.6%, a sensitivity of 67.5% and a specificity of 99.5% compared to CBCT, PR was a reliable method for the diagnosis of CAC. The overall detection rate for CAC was 27.8% across all age groups. Age (OR: 1.351; p = 0.021), the male sex (OR: 1.645; p = 0.006), arterial hypertension (OR: 2.217; p = < 0.001), heart disease (OR: 1.675; p = 0.006), hypercholesterolemia (OR: 1.904; p = 0.003) and chronic obstructive pulmonary disease (OR: 2.016; p = 0.036) were statistically significant risk factors. When correlated, neither history of stroke nor nicotine abuse showed any statistical significance. CONCLUSIONS: Due to the capabilities of PR in the diagnosis of CAC, dentists can play a vital role in the early diagnosis of vascular disease. Awareness should therefore be raised among dentists regarding the detection of CAC in patients over 60 years of age, with a particular focus on those with arterial hypertension and hypercholesterolaemia.

A novel approach to microsurgical teaching in head and neck surgery leveraging modern 3D technologies.

The anatomically complex and often spatially restricted conditions of anastomosis in the head and neck region cannot be adequately reproduced by training exercises on current ex vivo or small animal models. With the development of a Realistic Anatomical Condition Experience (RACE) model, complex spatial-anatomical surgical areas and the associated intraoperative complexities could be transferred into a realistic training situation in head and neck surgery. The RACE model is based on a stereolithography file generated by intraoperative use of a three-dimensional surface scanner after neck dissection and before microvascular anastomosis. Modelling of the acquired STL file using three-dimensional processing software led to the model's final design. As a result, we have successfully created an economical, sustainable and realistic model for microsurgical education and provide a step-by-step workflow that can be used in surgical and general medical education to replicate and establish comparable models. We provide an open source stereolithography file of the head-and-neck RACE model for printing for educational purposes. Once implemented in other fields of surgery and general medicine, RACE models could mark a shift in medical education as a whole, away from traditional teaching principles and towards the use of realistic and individualised simulators.

Molecular Markers Are Associated with Onset of Radioiodine Refractoriness in Patients with Papillary Thyroid Carcinoma.

The onset of radioiodine-refractory thyroid carcinoma (RR-TC) is a negative predictor of survival and has been linked to the presence of BRAFV600E mutations in papillary thyroid cancer. We aimed to identify further genetic alterations associated with RR-TC. Methods: We included 38 patients with papillary thyroid cancer who underwent radioiodine imaging and 18F-FDG PET/CT after total thyroidectomy. The molecular profile was assessed by next-generation sequencing. The time to the onset of RR-TC for different genetic alterations was compared using the log-rank test. Results: The median onset to RR-TC was 0.7 and 19.8 mo in patients with and without, respectively, telomerase reverse transcriptase promoter mutations (P = 0.02) and 1.7 and 19.8 mo in patients with and without, respectively, a tumor protein 53 mutation (P < 0.01). This association was not observed for BRAFV600E mutations (P = 0.49). Conclusion: Our data show a significant association between the onset of RR-TC and mutations in telomerase reverse transcriptase promoter and tumor protein 53, indicating the need for a more extensive diagnostic workup in these patients. Certain genetic changes put patients with thyroid cancer at risk of developing cancer spread that does not respond to radioiodine therapy.

Quantification performance of silicon photomultiplier-based PET for small 18F-, 68Ga- and 124I-avid lesions in the context of radionuclide therapy planning.

PURPOSE: The aim of this study was to investigate conditions for reliable quantification of sub-centimeter lesions with low18F,68Ga, and124I uptake using a silicon photomultiplier-based PET/CT system. METHODS: A small tumor phantom was investigated under challenging but clinically realistic conditions resembling prostate and thyroid cancer lymph node metastases (6 spheres with 3.7-9.7 mm in diameter, 9 different activity concentrations ranging from about 0.25-25 kBq/mL, and a signal-to-background ratio of 20). Radionuclides with different positron branching ratios and prompt gamma coincidence contributions were investigated. Maximum-, contour-, and oversize-based partial volume effect (PVE) correction approaches were applied. Detection and quantification performance were estimated, considering a ±30 % deviation between imaged-derived and true activity concentrations as acceptable. A standard and a prolonged acquisition time and two image reconstruction algorithms (time-of-flight with/without point spread function modelling) were analyzed. Clinical data were evaluated to assess agreement of PVE-correction approaches indicating lesion quantification validity. RESULTS: The smallest 3.7-mm sphere was not visible. If the lesions were clearly observed, quantification was, except for a few cases, acceptable using contour- or oversized-based PVE-corrections. Quantification accuracy did not substantially differ between 18F, 68Ga, and 124I. No systematic differences between the analyzed reconstruction algorithms or shorter and larger acquisition times were observed. In the clinical evaluation of 20 lesions, an excellent statistical agreement between oversize- and contour-based PVE-corrections was observed. CONCLUSIONS: At the lower end of size (<10 mm) and activity concentration ranges of lymph-node metastases, quantification with reasonable accuracy is possible for 18F, 68Ga, and 124I, possibly allowing pre-therapeutic lesion dosimetry and individualized radionuclide therapy planning.

Needs assessment in community-dwelling older adults toward digital interventions to promote physical activity: Cross-sectional survey study.

Background: Tackling physical inactivity represents a key global public health challenge. Strategies to increase physical activity (PA) are therefore warranted. Despite the rising availability of digital interventions (DIs), which offer tremendous potential for PA promotion, there has been inadequate attention to the special needs of older adults. Objective: The aim was to investigate community-dwelling older adults' needs, requirements, and preferences toward DIs to promote PA. Methods: The target population of this cross-sectional study was community-dwelling older adults (≥60 years old) within German-speaking Switzerland. Potential respondents were informed about the study and sent a link to a self-developed and self-administered online survey by our cooperating institutions. Results: Overall, 922 respondents who completed the online survey were included in the final analysis. The mean age of the sample was 72 years (SD 6.4, range 60-98). The preferred delivery mode of DIs to promote PA was a website (428/922, 46.4%) and 80.3% (740/922) preferred video-based structures. Most respondents expressed the need for personal access, personal goals, personal messages, and a personal contact in case of problems or questions (585/817, 71.6%; 546/811, 67.3%; 536/822, 65.2%; 536/822, 65.2%). Memory training, psychological wellbeing, and nutrition were mainly rated as relevant additional content of DIs to promote PA (690/849, 81.2%; 661/845, 78.2%, 619/849, 72.9%). Conclusion: Community-dwelling older adults may be willing to use DIs to promote PA in the long term, but this study identified particular needs and requirements in terms of design, technological realization, delivery mode, support, and individualization/personalization among the sample. Our results can inform future developments of DIs to promote PA specifically tailored to older adults. However, caution is warranted in interpreting the findings due to the sample's high PA and education levels.

An ex vivo model for education and training of unilateral cleft lip surgery.

BACKGROUND: Unilateral cleft lip surgery is a complex procedure, and the outcome depends highly on the surgeon's experience. Digital simulations and low-fidelity models seem inadequate for effective surgical education and training. There are only few realistic models for haptic simulation of cleft surgery, which are all based on synthetic materials that are costly and complex to produce. Hence, they are not fully available to train and educate surgical trainees. This study aims to develop an inexpensive, widely available, high-fidelity, ex vivo model of a unilateral cleft lip using a porcine snout disc. METHODS: A foil template was manufactured combining anatomical landmarks of the porcine snout disc and the anatomical situation of a child with a unilateral cleft. This template was used to create an ex vivo model of a unilateral cleft lip from the snout disc. Millard II technique was applied on the model to proof its suitability. The individual steps of the surgical cleft closure were photo-documented and three-dimensional scans of the model were analysed digitally. Sixteen surgical trainees were instructed to create a unilateral cleft model and perform a unilateral lip plasty. Their self-assessment was evaluated by means of a questionnaire. RESULTS: The porcine snout disc proved highly suitable to serve as a simulation model for unilateral cleft lip surgery. Millard II technique was successfully performed as we were able to perform all steps of unilateral cleft surgery, including muscle suturing. The developed foil-template is reusable on any porcine snout disc. The creation of the ex vivo model is simple and inexpensive. Self-assessment of the participants showed a strong increase in comprehension and an eagerness to use the model for surgical training. CONCLUSIONS: A porcine snout disc ex vivo model of unilateral cleft lips was developed successfully. It shows many advantages, including a haptic close to human tissue, multiple layers, low cost, and wide and rapid availability. It is therefore very suitable for teaching and training beginners in cleft surgery and subsequently improving surgical skills and knowledge. Further research is needed to finally assess the ex vivo model's value in different stages of the curriculum of surgical residency.

Correlation of the apparent diffusion coefficient with the standardized uptake value in meningioma of the skull plane using [68]Ga-DOTATOC PET/MRI.

PURPOSE: To evaluate a correlation between an MRI-specific marker for cellular density [apparent diffusion coefficient (ADC)] and the expression of Somatostatin Receptors (SSTR) in patients with meningioma of the skull plane and orbital space. METHODS: 68 Ga-DOTATOC PET/MR imaging was performed in 60 Patients with suspected or diagnosed meningiomas of the skull base and eye socket. Analysis of ADC values succeeded in 32 patients. ADC values (ADC mean and ADC min ) were analyzed using a polygonal region of interest. Tracer-uptake of target lesions was assessed according to corresponding maximal (SUV max ) and mean (SUV mean ) values. Correlations between assessed parameters were evaluated using the Pearson correlation coefficient. RESULTS: One out of 32 patients (3%) was diagnosed with lymphoma by histopathological examination and therefore excluded from further analysis. Median ADC mean amounted to 822 × 10 -5  mm²/s -1 (95% CI: 570-1497) and median ADC min was 493 × 10 -5 mm 2 /s -1 (95% CI: 162-783). There were no significant correlations between SUV max and ADC min (r = 0.60; P  = 0.76) or ADC mean (r = -0.52; P  = 0.79), respectively. However, Pearson's test showed a weak, inverse but insignificant correlation between ADC mean and SUV mean (r = -0.33; P  = 0.07). CONCLUSION: The presented data displays no relevant correlations between increased SSTR expression and cellularity in patients with meningioma of the skull base. SSTR-PET and DWI thus may offer complementary information on tumor characteristics of meningioma.

Bilobar Radioembolization Carries the Risk of Radioembolization-Induced Liver Disease in the Treatment of Advanced Hepatocellular Carcinoma: Safety and Efficacy Comparison to Systemic Therapy with Atezolizumab/Bevacizumab.

Recommended treatment options for advanced-stage hepatocellular carcinoma (HCC) include systemic therapy (ST) and trans-arterial radioembolization (TARE) with Yttrium-90 (Y90). Before the approval of immune-checkpoint inhibitors, a similar safety profile was reported for TARE and ST with tyrosine kinase inhibitors (TKI). However, whole-liver treatment and underlying cirrhosis were identified as risk factors for potentially lethal radioembolization-induced liver disease (REILD). Therefore, the safety and efficacy of TARE and ST with atezolizumab/bevacizumab were compared in patients with advanced HCC involving at least both liver lobes in a retrospective real-world cohort. In total, 74 patients with new or recurrent advanced-stage HCC (BCLC stage B/C) were included if treated with either bilobar TARE (n = 33) or systemic combination therapy with atezolizumab plus bevacizumab (n = 41). Most patients had compensated liver function (90.5% were classified as Child-Pugh Score A, 73% as ALBI Grade 1) at baseline. Although not significant, patients treated with ST showed a more prolonged overall survival than those treated with Y90 TARE (7.1 months vs. 13.0 months, p = 0.07). While a similar disease control rate could be achieved with bilobar TARE and atezolizumab/bevacizumab, in the TARE group, overall survival was curtailed by the occurrence of REILD. In patients with underlying liver cirrhosis, the liver function at baseline was a predictor for REILD.

An ex vivo model for education and training of bilateral cleft lip surgery.

BACKGROUND: Bilateral cleft lip surgery is very challenging and requires a high level of skill, knowledge and experience. Existing high-fidelity simulation models that can be used by novice cleft surgeons to gain experience and expand their knowledge are rare and expensive. In this study, we developed a bilateral cleft lip model using porcine snout discs, which are available anywhere and inexpensive. METHODS: Anatomic reference points of a patient with a bilateral cleft lip were superimposed with landmarks of the porcine snout disc on a foil template. The template was used to construct an ex vivo bilateral cleft lip model. Surgery was performed on the model according to Millard and the surgical steps were photodocumented analogous to two clinical cases of bilateral cleft lip surgery. The suitability of the model was further tested by twelve participants and evaluated using self-assessment questionnaires. RESULTS: The bilateral cleft lip ex vivo model made of a porcine snout disc proved to be a suitable model with very low cost and ease of fabrication, as the template is reusable on any snout disc. The Millard procedure was successfully performed and the surgical steps of the lip plasty were simulated close to the clinical situation. Regarding the nasal reconstruction, the model lacks three-dimensionality. As a training model, it enhanced the participants comprehension of cleft surgery as well as their surgical skills. All participants rated the model as valuable for teaching and training. CONCLUSIONS: The porcine snout discs can be used as a useful ex vivo model for bilateral cleft lip surgery with limitations in the construction of the nose, which cannot be realistically performed with the model due to anatomical differences with humans. Benefits include a realistic tissue feel, the simulation of a multi-layered lip construction, a wide and rapid availability and low cost. This allows the model to be used by novice surgeons also in low-income countries. It is therefore useful as a training model for gaining experience, but also as a model for refining, testing and evaluating surgical techniques for bilateral lip plasty.

Postoperative Changes in Systemic Immune Tolerance Following Major Oncologic versus Minor Maxillofacial Surgery.

BACKGROUND: There is increasing evidence of the benefits of adjuvant and neoadjuvant immunotherapy in the treatment of solid malignancies like oral squamous cell carcinoma (OSCC). To optimize (neo-)adjuvant treatment, the systemic immunomodulatory effects of tumor surgery itself need to be considered. Currently, there is little evidence on the immunological effects of major surgery, such as free microvascular flap reconstruction. The current study aims to analyze how and to what extent maxillofacial surgery affects systemic parameters of immune tolerance. METHODS: A total of 50 peripheral whole blood samples from patients (Group 1 (G1) = extensive OSCC surgery; Group 2 (G2) = free flap reconstruction without persistent malignant disease; Group 3 (G3) = minor maxillofacial surgery) undergoing surgery were included for real-time quantitative polymerase chain reaction (RT-qPCR) to examine changes in mRNA expression of the biomarkers IL-6, IL-10, FOXP3, and PD-L1. Blood samples were taken immediately before and after surgery as well as on the second, fourth, and tenth postoperative days. Differences in mRNA expression between groups and time points were calculated using statistical tests, including Mann-Whitney U-test and Pearson correlation analysis. RESULTS: Comparing postoperative expression of G1 and G3, there was a significantly higher PD-L1 expression (p = 0.015) in G1 compared to G3 and a significantly lower IL-6 (p = 0.001) and FOXP3 (p = 0.016) expression. Interestingly, IL-10 expression was higher pre- (0.05) and postoperative (p < 0.001) in G1 compared to G3. Additionally, in G1, there was a significant overexpression of IL-10 post-surgery compared to the preoperative value (p = 0.03) and a downregulated expression of FOXP3 between pre- and 2 d post-surgery (p = 0.04). Furthermore, there was a significant correlation between the duration of surgery and the perioperative expression changes of the analyzed biomarkers. As the duration of surgery increased, the expression of IL-10 and PD-L1 increased, and the expression of IL-6 and FOXP3 decreased. CONCLUSION: Extensive surgery in OSCC patients is associated with a transient shift toward postoperative systemic immune tolerance compared with patients undergoing minor surgery. However, even extensive surgery causes no signs of long-lasting systemic immunosuppression. The degree of immune tolerance that occurred was associated with the duration of surgery. This supports efforts to minimize the duration of surgery.

Prognostic Implications of PET-Derived Tumor Volume and Uptake in Patients with Neuroendocrine Tumors.

Historically, molecular imaging of somatostatin receptor (SSTR) expression in patients with neuroendocrine tumors (NET) was performed using SSTR scintigraphy (SRS). Sustained advances in medical imaging have led to its gradual replacement with SSTR positron-emission tomography (SSTR-PET). The higher sensitivity in comparison to SRS on the one hand and conventional cross-sectional imaging, on the other hand, enables more accurate staging and allows for image quantification. In addition, in recent years, a growing body of evidence has assessed the prognostic implications of SSTR-PET-derived prognostic biomarkers for NET patients, with the aim of risk stratification, outcome prognostication, and prediction of response to peptide receptor radionuclide therapy. In this narrative review, we give an overview of studies examining the prognostic value of advanced SSTR-PET-derived (semi-)quantitative metrics like tumor volume, uptake, and composite metrics. Complementing this analysis, a discussion of the current trends, clinical implications, and future directions is provided.