Artificial Intelligence in Medical Education: Comparative Analysis of ChatGPT, Bing, and Medical Students in Germany.

BACKGROUND: Large language models (LLMs) have demonstrated significant potential in diverse domains, including medicine. Nonetheless, there is a scarcity of studies examining their performance in medical examinations, especially those conducted in languages other than English, and in direct comparison with medical students. Analyzing the performance of LLMs in state medical examinations can provide insights into their capabilities and limitations and evaluate their potential role in medical education and examination preparation. OBJECTIVE: This study aimed to assess and compare the performance of 3 LLMs, GPT-4, Bing, and GPT-3.5-Turbo, in the German Medical State Examinations of 2022 and to evaluate their performance relative to that of medical students. METHODS: The LLMs were assessed on a total of 630 questions from the spring and fall German Medical State Examinations of 2022. The performance was evaluated with and without media-related questions. Statistical analyses included 1-way ANOVA and independent samples t tests for pairwise comparisons. The relative strength of the LLMs in comparison with that of the students was also evaluated. RESULTS: GPT-4 achieved the highest overall performance, correctly answering 88.1% of questions, closely followed by Bing (86.0%) and GPT-3.5-Turbo (65.7%). The students had an average correct answer rate of 74.6%. Both GPT-4 and Bing significantly outperformed the students in both examinations. When media questions were excluded, Bing achieved the highest performance of 90.7%, closely followed by GPT-4 (90.4%), while GPT-3.5-Turbo lagged (68.2%). There was a significant decline in the performance of GPT-4 and Bing in the fall 2022 examination, which was attributed to a higher proportion of media-related questions and a potential increase in question difficulty. CONCLUSIONS: LLMs, particularly GPT-4 and Bing, demonstrate potential as valuable tools in medical education and for pretesting examination questions. Their high performance, even relative to that of medical students, indicates promising avenues for further development and integration into the educational and clinical landscape.

Clinical Characteristics, Diagnostic Approach and Outcome of Thyroid Incidental Findings vs. Clinically Overt Thyroid Nodules: An Observational Single-Centre Study.

Context: Thyroid nodules are common and can present as clinically overt nodules (visible, palpable or symptomatic nodules) and so-called incidentalomas (coincidental findings on imaging techniques). The majority are benign but recognizing clinically relevant nodules remains a challenge. Current Dutch guidelines recommend to refrain from additional diagnostic testing in incidentalomas other than FDG-PET-incidentalomas, unless there are suspicious clinical and/or sonographic features. However, there is no consensus on the further approach and no "real-life" data on the outcome of such an approach. Objective: To compare clinical characteristics, diagnostic approaches and clinical outcome between patients referred with thyroid incidentalomas and non-incidentalomas at one academic referral thyroid clinic. Methods: Clinical and demographical characteristics, diagnostic and therapeutic approaches and outcome were retrospectively obtained from the files of all patients newly referred because of thyroid incidentalomas or non-incidentalomas to our institution (between March 2011 and January 2017). Subsequently, the data were compared between both groups. Results: In total, 351 patients (64.3%) were referred because of non-incidentalomas and 195 (35.7%) because of incidentalomas. Incidentalomas were smaller (48.7% <2 cm) than non-incidentalomas (23.4% <2 cm). Furthermore, incidentalomas were less often symptomatic (15.9 vs. 42.7% p < 0.001). Fine-needle aspiration was performed in a similar percentage of the patients in the two groups (62.6% of incidentalomas vs. 69.8% in non-incidentaloma, p = 0.08). Significantly less malignancies were found among incidentalomas compared to non-incidentalomas (5.1% vs. 11.1%, p = 0.019). Moreover, significantly more malignancies occurred in PET-incidentalomas than non-PET-incidentalomas (11.8% vs. 2.8%, p = 0.023). In fact, the proportion of malignancies in PET-incidentalomas and non-incidentalomas was similar (11.8% vs. 11.1%, p = 0.895). Stability or decrease in size was observed in 96.5% of nodules receiving ultrasound follow-up. Conclusions: Patients with small asymptomatic thyroid incidentalomas represent an important proportion of the patients referred for additional diagnostic evaluation. The risk of malignancy in these patients is lower than in those with symptomatic palpable lesions, particularly in the patients with incidentalomas discovered on CT, MRI or US. Our findings support the current recommendations from the Dutch guidelines to not indiscriminately perform additional analysis and treatment on all incidentalomas, but prioritize this to FDG-PET-incidentalomas and clinically relevant non-PET-incidentalomas. Moreover, US features can further refine the selection of the patients who require immediate FNAC and/or surgery.

Integrated Bioluminescent Immunoassays for High-Throughput Sampling and Continuous Monitoring of Cytokines.

Immunoassays show great potential for the detection of low levels of cytokines, due to their high sensitivity and excellent specificity. There is a particular demand for biosensors that enable both high-throughput screening and continuous monitoring of clinically relevant cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα). To this end, we here introduce a novel bioluminescent immunoassay based on the ratiometric plug-and-play immunodiagnostics (RAPPID) platform, with an improved intrinsic signal-to-background and an >80-fold increase in the luminescent signal. The new dRAPPID assay, comprising a dimeric protein G adapter connected via a semiflexible linker, was applied to detect the secretion of IL-6 by breast carcinoma cells upon TNFα stimulation and the production of low concentrations of IL-6 (∼18 pM) in an endotoxin-stimulated human 3D muscle tissue model. Moreover, we integrated the dRAPPID assay in a newly developed microfluidic device for the simultaneous and continuous monitoring of changes in IL-6 and TNFα in the low-nanomolar range. The luminescence-based read-out and the homogeneous nature of the dRAPPID platform allowed for detection with a simple measurement setup, consisting of a digital camera and a light-sealed box. This permits the usage of the continuous dRAPPID monitoring chip at the point of need, without the requirement for complex or expensive detection techniques.

COVID-19 measures as an opportunity to reduce the environmental footprint in orthopaedic and trauma surgery.

Background: Climate change and its consequences on our everyday life have also tremendous impacts on public health and the health of each individual. The healthcare sector currently accounts for 4.4% of global greenhouse gas emissions. The share of the emissions in the health care system caused by the transportation sector is 7%. The study analyses the effect of video consultation on the CO2 emissions during the Covid-19 pandemic in an outpatient clinic of the department of orthopaedics and traumatology surgery at a German university hospital. Methods: The study participants were patients who obtained a video consultation in the period from June to December 2020 and voluntarily completed a questionnaire after the consultation. The type of transport, travel time and waiting time as well as patient satisfaction were recorded by questionnaire. Results: The study comprised 51 consultations. About 70% of respondents would have travelled to the clinic by car. The reduction in greenhouse gas emissions of video consultations compared to a face-to-face presentation was 97% in our model investigation. Conclusion: The video consultation can be a very important part of the reduction of greenhouse gas emissions in the health care system. It also saves time for the doctor and patient and can form an essential part of individual patient care.

APP-guided assessment of acetabular defects in hip revision arthroplasty: a structured approach to a complex situation.

INTRODUCTION: Acetabular defect recognition and classification remains a challenging field of practice for orthopedic surgeons. Recently, the Acetabular Defect Classification (ADC) has been introduced to provide a reliable, reproducible and intuitive classification system. In order to improve ease of use and efficiency of the ADC, a browser-based application has been created. We hypothesized that the ADC application can improve rating performance of non-specialists (medical students) to achieve good inter- and intra-rater agreement and will compare favorable to the results of specialists (experienced surgeons) without the help of the application. MATERIALS AND METHODS: The ADC is based on the integrity of the acetabular rim and the supporting structures. It consists of four main types of defects ascending in severity. These defects are further subdivided in A-C, narrowing down defect location. 80 randomized radiographs were graded according to ADC by three non-specialists (medical students) with help of the ADC application and by three specialists (orthopedic surgeons) without help of the application to evaluate the difference in inter-rater agreement between groups. To account for intra-rater agreement, the rating process was repeated after a reasonable wash-out period. RESULTS: Inter-rater and intra-rater agreement within the non-specialist group rated lower when compared to the specialist group while still falling into the good agreement range. The student group presented with k values of 0.61 for inter-rater agreement and 0.68 for intra-rater agreement, while the surgeon group displayed k values of 0.72 for inter-rater agreement and 0.83 for intra-rater agreement. CONCLUSION: The app-guided assessment of acetabular defects offers a promising innovative approach to simplify complex situations. It makes the challenging field of acetabular revision arthroplasty more approachable especially for less experienced surgeons and offers insight and guidance in the planning stage as well as intra-operative setting.

Practicability of a Virtual Consultation to Evaluate the Shoulder Joint. / Durchführbarkeit einer digitalen Sprechstunde zur Untersuchung des Schultergelenkes.

OBJECTIVE: In the course of the corona pandemic, resource conservation and the protection of further infections have made it necessary to break new ground in the organisation of orthopaedic and trauma surgery consultations. One solution is consistent digitisation and the offer of video consultation hours. In this study, non-contact examination of patients with shoulder disorders is described and critically examined. METHODS: Thirty patients who presented with pathologies of the shoulder joint in a university outpatient clinic were subjected to a physical examination in a conventional and contactless manner. The data obtained on mobility, function and provocation test of both examinations were compared to draw conclusions about the virtual feasibility. RESULTS: 46% of the patients suffered from a traumatic shoulder lesion, and 54% showed degenerative lesions. The assessment of mobility showed a high correlation of 70 - 90% between the two examinations. Common tests to evaluate the supraspinatus, infraspinatus, subscapularis and the long head of the biceps could be adequately performed in a contactless version by more than three quarters of the patients, but with low-to-moderate performance values. CONCLUSION: Contact-less examination is particularly disadvantageous when evaluating stability criteria. For the medical history and functional test, there were no significant differences between the classic consultation and contactless consultation. Although virtual consultation is a widespread and valuable addition in pandemic times, it cannot replace a safe assessment and indication by personal examination.

Open Access Redefined: Survey Data and Literature Study on the Impact of Sci-Hub in Orthopaedic Research.

BACKGROUND: Since Alexandra Elbanyan founded Sci-Hub in 2011, the website has been used by a growing number of researchers worldwide. Sci-Hub is a so-called shadow library or guerrilla open access format bypassing publishers' paywalls, giving everyone free access to scientific papers. Until today, there have been no publications about usage by orthopaedic and trauma surgeons of Sci-Hub or other "pirate sites" and how it may influence their work. MATERIALS AND METHODS: Orthopaedic and trauma surgeons of four university hospitals in Germany and Europe were consulted using a standardised questionnaire containing multiple items about the use and evaluation of Sci-Hub. In addition, the Medline and Cochrane databases were screened for all studies related to Sci-Hub. Two reviewers independently reviewed all articles and the references of these articles. RESULTS: Of all orthopaedic surgeons consulted, 69% knew of Sci-Hub and 66.7% used it on a regular basis. Of the younger participants (< 45 years old), 77% knew the webpage, while only 25% of older participants (> 45 years old) knew the webpage. Ninety percent found the quality of their citation and research had been enhanced since using Sci-Hub. On a scale of 1 to 10, user-friendliness was rated with a mean rating of 7.58 (95% CI: 7.262-7.891). Ethical or legal concerns among users seem mixed. On a scale of 1 (no concerns) to 5 (many concerns), the mean score was 2.39 (95% CI: 2.154-2.615). Of doctors using Sci-Hub, 89% would recommend it to other colleagues. CONCLUSION: The quality and number of articles in Sci-Hub is outstanding, and the rate of young researchers using the website is high. The most important shift in literature research for decades is a phenomenon mostly used by young researchers and is not the subject of current research itself. Sci-Hub may have already changed how orthopaedic research works.

Cross-sectoral Analysis of 1.4 Million AOK-insured Patients with Back Pain in Baden-Württemberg - What Influence does Outpatient Specialist Care Have? / Sektorenübergreifende Rückenschmerz-Versorgungsanalyse von 1,4 Mio. AOK-Versicherten in Baden-Württemberg ­ welchen Einfluss hat die ambulante fachärztliche Versorgung?

BACKGROUND: Back pain is one of the leading causes of disability globally and the most common musculoskeletal pain in Germany. The lifetime prevalence of back pain ranges from 74% to 85%, and the point prevalence ranges from 32% to 49%. One in five individuals with statutory health insurance visits a doctor at least once a year for back pain, and 1 in 20 individuals is on sick leave at least once a year. The question as to what extent can different outpatient care concepts substantially contribute to improving care and avoiding inpatient hospital treatment has repeatedly been the subject of controversial political discussions. This study aimed to present a description of the reality of care in Baden-Württemberg (BW), Germany, based on claims data. MATERIAL AND METHODS: Anonymised routine billing data of AOK Baden-Württemberg were analysed in compliance with data protection regulations. The billing data cover the outpatient and inpatient care sectors. All AOK patients in BW who received at least one ICD10 diagnosis from their physician in the first half of 2015 were considered for the analysis. Patients with at least one diagnosis of back pain were evaluated as patients with back pain, whereby the assignment to the diagnosis group of specific or non-specific back pain was made based on the code. RESULTS: In the first half of 2015, nearly 988 925 patients with back pain were registered in the 6696 primary care clinics in BW, approximately 302 524 patients in 1172 orthopaedic clinics and 17 043 patients in 89 neurosurgical clinics. Primary care clinics reported back pain diagnosis in 34.6%, orthopaedic clinics in 51.9% and neurosurgical clinics in 78.6% of cases. Primary care clinics diagnosed a specific cause in approximately one-third of patients with back pain, orthopaedic clinics in approximately 40% of their patients and neurosurgery clinics in one in two cases. Overall, approximately 1.2% of 1.3 million patients with back pain (January to December 2015 in BW) were hospitalised. Inpatient therapy consisted of surgical therapy and conservative therapy. Nucleotomy, decompression and spondylodesis were the three most common surgical procedures performed. Pain medication and remedy prescriptions decreased pain after spinal surgery. There are significant regional differences in referral and surgery rates. The mean inpatient referral rate was 535 of 100 000 AOK insurants, and the median was 536 of 100 000 AOK insurants. The mean surgery rate among all admitted patients with back pain was 49.9%, and the median was 49.8%. CONCLUSION: The vast majority of patients with back pain are treated as outpatients. Only approximately 1.2% of all patients with back pain were treated as inpatients in 2015. Of these, approximately half underwent surgery. Spinal surgeries led to a decrease in pain medication and remedy prescription postoperatively. The three most frequent surgical procedures were 'decompression', 'excision of disc tissue' and 'spondylodesis'. There were significant regional differences.

Changes of static and dynamic spine alignment in patients with severe haemophilia.

INTRODUCTION: Haemophilic arthropathy results in a restricted range of motion and pain that often affects gait. The effect of these gait changes on spinal posture has not been studied. AIM: To evaluate whether the altered joint situation in patients with haemophilia (PwH) leads to compensatory mechanisms evident in the trunk and spine, considering static and dynamic conditions. METHODS: PwH and healthy controls (20-65 years) were examined using rasterstereography in a controlled cohort study. Analysis was performed in static and dynamic conditions in regard to gait phases. Joint status was determined using the Haemophilia Joint Health Score (HJHS). RESULTS: Static measurements showed no group differences in PwH (n = 40) compared to healthy controls (n = 40) except pelvic torsion (median [25%-quartile;75%-quartile]: -1.9[-3.2;.9]° vs. .5[-1.1;1.9]°; P = .007). In contrast, under dynamic conditions PwH showed significantly higher trunk inclination and lower apex lumbar lordosis in all gait phases. Additionally, pelvic torsion was increased in mid stance and terminal swing. Considering joint status, PwH had a higher global HJHS (23.5[13.0;30.0] vs. 3.0[1.0;5.0]; P<.001). A significant moderate correlation was shown between the HJHS mobility score and spine parameters (r = .228-.588; P<.05). CONCLUSION: Degenerative joint changes in PwH lead to altered spine posture during gait. A reason could be the reduced mobility in the affected joint. Changes in spinal and pelvic posture lead to higher structural burdens; therefore, clinicians should focus on posture of spinal column during gait in daily treatment.

Spine Examination during COVID-19 Pandemic via Video Consultation. / Telemedizinische Wirbelsäulenuntersuchung während der COVID-19-Pandemie.

INTRODUCTION: During the current COVID-19 pandemic video consultations are increasingly common in order to minimize the risk of infection for staff and patients. The aim of this study was to evaluate the feasibility of a spine examination via video. METHODS: A total of 43 patients were recruited. Each participant underwent a video-based (VB) and a conventional face-to-face (FTF) spine examination. Pain intensity, active range of motion, inspection, a neurophysiologic basic exam and provocations tests were evaluated using video-based and face-to-face methods. RESULTS: The intra-rater reliability (IRR) was measured between both examinations. Good to very good IRR values were obtained in inspection (Kappa between 0,752 und 0,944), active range of motion and basic neurophysiological examination (Kappa between 0,659 und 0,969). Only moderate matches were found in specific provocation tests (Kappa between 0,407 und 0,938). A video-based spine examination is a reliable tool for measuring pain intensity, active range of motion and a basic neurophysiologic exam. CONCLUSION: A basic spine examination during a video consultation is possible. A good agreement of the test results between video-based and face-to-face examination could be found.

Examining the Hand in the Video Consultation. / Die Untersuchung der Hand in der Videosprechstunde.

BACKGROUND: Video consultations could support patient care in hand surgery during social distancing in the COVID-19 era. According to the literature, images of hand and fingers can support telediagnosis in hand emergencies. We present this feasibility study on online video consultation in hand surgery. METHODS: A structured examination was designed to query the medical history and examine motor skills, sensitivity, strength and function tests of the hand. Thirty examinations on both hands were carried out by online video consultation, then in direct contact and compared with each other. RESULTS: With 4560 evaluated range of movement of the hand and finger joints, there was a high correlation between the measurement methods of R = 0.995 (p < 0.0001, confidence interval 0.9946 - 0.9954). In the video-based examination, 84.6% of the measured values showed a deviation of less than 5° compared to the direct examination, 92.8% less than 10° deviation. Good accordance was also found in the patient's medical history. An estimating examination of sensitivity, function and strength during video examination is feasible with simple auxiliary aids. Deficits are evident in the detection of scars, in function tests and the absence of haptic findings. CONCLUSION: Online video consultation allows hand examination with sufficient documentation of hand and finger movements (range of motion) and proper evaluation of symptoms. It cannot replace direct examination but complement patient care in hand surgery even beyond the current COVID-19 pandemic.

Machine Learning Explainability in Breast Cancer Survival.

Machine Learning (ML) can improve the diagnosis, treatment decisions, and understanding of cancer. However, the low explainability of how "black box" ML methods produce their output hinders their clinical adoption. In this paper, we used data from the Netherlands Cancer Registry to generate a ML-based model to predict 10-year overall survival of breast cancer patients. Then, we used Local Interpretable Model-Agnostic Explanations (LIME) and SHapley Additive exPlanations (SHAP) to interpret the model's predictions. We found that, overall, LIME and SHAP tend to be consistent when explaining the contribution of different features. Nevertheless, the feature ranges where they have a mismatch can also be of interest, since they can help us identifying "turning points" where features go from favoring survived to favoring deceased (or vice versa). Explainability techniques can pave the way for better acceptance of ML techniques. However, their evaluation and translation to real-life scenarios need to be researched further.

'It is not entirely healthy.' A qualitative study into public appraisals of uncertain risks of chemical substances in food.

For some chemical substances in food, scientific uncertainty prevents definitive statements about the presence of risk for human health. In this qualitative study, we explored the public's understanding and risk appraisal of these substances. During semi-structured interviews, participants from the public were presented with inconclusive risk information about either a food additive or one of two food contaminants. Findings show that interviewees had no prior knowledge and constructed their risk appraisal on the spot. Results suggest that generic and case specific beliefs and inferences affect understanding and appraisal. Respondents' interpretations of the risk messages used in this study were often not in line with what the message intended to convey. In addition, specific use of scientific jargon was associated with increased risk. In general, respondents were more apprehensive about the presence of the chemical in food than that they were worried about the chance of experiencing health effects.

PET-Based Human Dosimetry of 68Ga-NODAGA-Exendin-4, a Tracer for ß-Cell Imaging.

68Ga-NODAGA-exendin-4 is a promising tracer for ß-cell imaging using PET/CT. Possible applications include preoperative visualization of insulinomas and discrimination between focal and diffuse forms of congenital hyperinsulinism. There is also a significant role for this tracer in extending our knowledge on the role of ß-cell mass in the pathophysiology of type 1 and type 2 diabetes by enabling noninvasive quantification of tracer uptake as a measure for ß-cell mass. Calculating radiation doses from this tracer is important to assess its safety for use in patients (including young children) with benign diseases and healthy individuals. Methods: Six patients with hyperinsulinemic hypoglycemia were included. After intravenous injection of 100 MBq of the tracer, 4 successive PET/CT scans were obtained at 30, 60, 120, and 240 min after injection. Tracer activity in the pancreas, kidneys, duodenum, and remainder of the body were determined, and time-integrated activity coefficients for the measured organs were calculated. OLINDA/EXM software, version 1.1, was applied to calculate radiation doses using the reference adult male and female models and to estimate radiation doses to children. Results: The mean total effective dose for adults was very low (0.71 ± 0.07 mSv for a standard injected dose of 100 MBq). The organ with the highest absorbed dose was the kidney (47.3 ± 10.2 mGy/100 MBq). The estimated effective dose was 2.32 ± 0.32 mSv for an injected dose of 20 MBq in newborns. This dose decreased to 0.77 ± 0.11 mSv/20 MBq for 1-y-old children and 0.59 ± 0.05 mSv for an injected dose of 30 MBq in 5-y-old children. Conclusion: Our human PET/CT-based dosimetric calculations show that the effective radiation doses from the novel tracer 68Ga-NODAGA-exendin-4 are very low for adults and children. The doses are lower than reported for other polypeptide tracers such as somatostatin analogs (2.1-2.6 mSv/100 MBq) and are beneficial for application as a research tool, especially when repeated examinations are needed.

'All chemical substances are harmful.' public appraisal of uncertain risks of food additives and contaminants.

In toxicological health risk assessment, epistemic uncertainties (e.g. about a chemical's intrinsic properties or toxicity) often remain, preventing definitive statements about whether a chemical constitues a risk. In this study, we analyzed public appraisals of uncertain risks of food additives and contaminants. We identified three major characteristics of public appraisal. First, hazard appraisals differed consistently from risk appraisals: respondents were less disturbed by a possible health risk than by the mere presence of the chemical substance in food. Second, while a majority understood that exposure determines whether a chemical constitutes a risk, many respondents thought that all chemicals are equally harmful. This suggests a mismatch between beliefs about exposure and beliefs about toxicity. Finally, the higher people valued certainty about food safety and the less they considered uncertainty about a risk acceptable, the more severe they appraised the presence of the chemical substance in food. This suggests that a mismatch between the level of uncertainty that people expect about food safety and the actual level of scientific uncertainty, affects how people evaluate the presence of chemical substances in food. Following the findings, implications for risk communication are discussed.

Diagnosis of peri-prosthetic loosening of total hip and knee arthroplasty using 18F-Fluoride PET/CT.

Periprosthetic loosening, either aseptic or induced by periprosthetic joint infection remains a major long term complication and challenge in orthopedics and trauma surgery. Sensitivity of potential loosening of the material and other causes of a painful prosthesis is essential for choosing the respective treatment option and providing the needed resources. 18F-Fluoride is a radiopharmaceutical which shows a high affinity to bone and a rapid blood clearance. The objective of this study was to assess 18F-Fluoride PET/CT´s sensitivity and specificity in diagnosing periprosthetic loosening in total hip and knee arthroplasty. We included 26 patients with 24 hip and 13 knee prostheses in our retrospective study with radiological or clinical suspicion of peri-prosthetic loosening at least one year after implantation. Results of 18F-Fluoride PET/CT imaging were compared with surgical results or clinical follow-up if surgery was not performed. On the basis of our data we found a sensitivity of 95.00 %, a specificity of 87.04 % and an accuracy of 89.19 % for 18F-Fluoride PET/CT. The results of our study show that 18F-Fluoride PET/CT is a useful and promising technique in diagnosing periprosthetic loosening of total hip and knee arthroplasties. Further investigation should focus on different uptake patterns of the isotope in periprosthetic joint infection and therefore distinguishing aseptic from septic loosening and enhancing the diagnostic value of this imaging method.

Exendin-4 analogs in insulinoma theranostics.

Insulinomas, neuroendocrine tumors arising from pancreatic beta cells, often show overexpression of the glucagon-like peptide-1 receptor. Therefore, imaging with glucagon-like peptide analog exendin-4 can be used for diagnosis and preoperative localization. This review presents an overview of the development and clinical implementation of exendin-based tracers for nuclear imaging, and the potential use of exendin-4 based tracers for optical imaging and therapeutic applications such as peptide receptor radionuclide therapy or targeted photodynamic therapy.

Succinylated Gelatin Improves the Theranostic Potential of Radiolabeled Exendin-4 in Insulinoma Patients.

Being highly expressed in insulinomas, the glucagonlike peptide-1 receptor (GLP-1R) is a potential target for diagnosis, localization, and treatment with the radiolabeled GLP-1R agonist exendin. Tracer accumulation in the kidneys, however, hampers accurate diagnostic visualization of pancreatic tissue and prohibits the therapeutic application of radiolabeled exendin for ß-cell-derived tumors. Therefore, we evaluated the ability of succinylated gelatin (Gelofusine) to reduce the renal accumulation of radiolabeled exendin in humans, and we performed dosimetric calculations to estimate the maximum absorbed insulinoma dose that could be achieved if exendin were to be used for peptide receptor radionuclide therapy. Methods: Ten healthy volunteers received 50 MBq of 111In-exendin-4, in combination with Gelofusine or saline, in a crossover design. SPECT/CT images were obtained after 24 h. The procedure was repeated 3 wk later. Uptake of 111In-exendin was determined by drawing regions of interest around the kidneys and in the pancreas. Planar scintigraphic 111In-exendin images of 5 insulinoma patients were used for dosimetry studies estimating the maximum insulinoma absorbed dose that could be achieved without causing radiotoxicity to other organs. Results: Gelofusine reduced the renal accumulation of 111In-exendin-4 by 18.1%, whereas the pancreatic uptake remained unchanged. In 3 of 10 subjects, the kidney uptake was reduced to such an extent that the pancreatic tail could be better discriminated from the kidney signal. Dosimetric estimations suggested that the insulinoma absorbed dose ranges from 30.3 to 127.8 Gy. This dose could be further increased to maximally 156.1 Gy if Gelofusine was used. Conclusion: We have shown that Gelofusine can reduce the renal accumulation of 111In-exendin-4 in humans. This reduction not only allows more accurate qualitative and quantitative analyses of radiolabeled exendin uptake in the tail region of the pancreas but also potentiates the safe delivery of a higher radiation dose to GLP-1R-positive tumors for therapy.

Detection and quantification of beta cells by PET imaging: why clinical implementation has never been closer.

In this issue of Diabetologia, Alavi and Werner ( https://doi.org/10.1007/s00125-018-4676-1 ) criticise the attempts to use positron emission tomography (PET) for in vivo imaging of pancreatic beta cells, which they consider as 'futile'. In support of this strong statement, they point out the limitations of PET imaging, which they believe render beta cell mass impossible to estimate using this method. In our view, the Alavi and Werner presentation of the technical limitations of PET imaging does not reflect the current state of the art, which leads them to questionable conclusions towards the feasibility of beta cell imaging using this approach. Here, we put forward arguments in favour of continuing the development of innovative technologies enabling in vivo imaging of pancreatic beta cells and concisely present the current state of the art regarding putative technical limitations of PET imaging. Indeed, far from being a 'futile' effort, we demonstrate that beta cell imaging is now closer than ever to becoming a long-awaited clinical reality.