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Background: We evaluated efficacy and toxicity of 68Ga-PSMA-Positron Emission Tomography/Computed Tomography (PET/CT)-directed stereotactic body radiotherapy and image-guided radiotherapy (SBRT/IGRT) for oligometastases of prostate cancer recurrences after previous surgery. Methods: Nineteen patients were analyzed within a prospective PET-registry study (064/2013BO1) and retrospectively analyzed (807/2017BO2) fulfilling the following inclusion criteria: biochemical recurrence after radical prostatectomy, ≤five 68Ga-PSMA-PET/CT positive lesions. Biochemical control was evaluated with EORTC (European Organization for Research and Treatment of Cancer)- and Phenix-definitions. Toxicity was scored according to CTCAE-criteria v. 4.03. Results: A total of 38 oligometastases (19 patients, 2 with re-treatment) were treated with SBRT/IGRT from October 2014 to July 2017. 68Ga-PSMA-PET/CT-positive lesions were detected on average 39 months (5–139) after prostatectomy (pT2b-3b pN0-1 cM0). Mean PSA (Prostate-specific antigen)-level at time of imaging reached 2.2 ng/mL (range 0.2–10.1). PET/CT-positive lesions were treated with different fractionation schedules reaching biological equivalent doses (BED) of 116.7–230.0 Gy. Concomitant androgen deprivation therapy (ADT) was given in seven patients. After a median follow-up of 17 months (4–42) all patients were alive. Estimated 1-year PSA- control (n = 19) reached 80.8% (Phenix) and 67.5% (EORTC). A PSA-decline (≥50%) was detected in 16/19 patients after radiotherapy. Higher graded G3+-acute toxicity did not occur. Temporary late G3-proctitis was detected in one patient. Conclusions: Reaching of nadir ≤0.1 or 0.2 ng/mL was associated by improved DMFS (distant metastases free survival) and could serve as a surrogate endpoint for RT of oligometastases after initial prostatectomy. Short term effects of 68Ga-PSMA-PET/CT-based ablative radiotherapy for oligometastases demonstrated an acceptable toxicity profile and favorable biochemical response. [ABSTRACT FROM AUTHOR]

The role and molecular mechanisms of intermittent fasting (IF) in non-alcoholic steatohepatitis (NASH) and its transition to hepatocellular carcinoma (HCC) are unknown. Here, we identified that an IF 5:2 regimen prevents NASH development as well as ameliorates established NASH and fibrosis without affecting total calorie intake. Furthermore, the IF 5:2 regimen blunted NASH-HCC transition when applied therapeutically. The timing, length, and number of fasting cycles as well as the type of NASH diet were critical parameters determining the benefits of fasting. Combined proteome, transcriptome, and metabolome analyses identified that peroxisome-proliferator-activated receptor alpha (PPARα) and glucocorticoid-signaling-induced PCK1 act co-operatively as hepatic executors of the fasting response. In line with this, PPARα targets and PCK1 were reduced in human NASH. Notably, only fasting initiated during the active phase of mice robustly induced glucocorticoid signaling and free-fatty-acid-induced PPARα signaling. However, hepatocyte-specific glucocorticoid receptor deletion only partially abrogated the hepatic fasting response. In contrast, the combined knockdown of Ppara and Pck1 in vivo abolished the beneficial outcomes of fasting against inflammation and fibrosis. Moreover, overexpression of Pck1 alone or together with Ppara in vivo lowered hepatic triglycerides and steatosis. Our data support the notion that the IF 5:2 regimen is a promising intervention against NASH and subsequent liver cancer., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim/introduction: Peptide receptor radionuclide therapy (PRRT) represents a cornerstone of treatment regimens for patients with low proliferative neuroendocrine tumors (NETs). However, in patients experiencing somatostatin receptor-positive NET with higher proliferation rates, a value and potential therapeutic benefit of PRRT as part of multimodal treatment approaches and potentially with addition of radiosensitizing agents has not yet been established., Patients and Methods: In this study, 20 patients with histologically confirmed gastroenteropancreatic (GEP) NET with proliferation rates (Ki67) between 15% and 55% were treated either with PRRT only (n = 10) or with a combination therapy (n = 10) comprising PRRT and capecitabine/temozolomide (CAP/TEM) for at least 2 consecutive cycles., Results: Disease control rate in patients treated with PRRT alone was 60% (40% stable disease and 20% partial response). Strikingly, in patients treated with PRRT in combination with radiosensitization (CAP/TEM), the disease control rate was 90% (20% stable disease and 70% partial response). The median progression-free survival in the PRRT only group was 12 months, whereas the median progression-free survival in the PRRT + CAP/TEM group was 26 months and has not been yet reached for all patients in the group during the observation period. The median disease-specific survival for patients with PRRT alone was 51 months, whereas this end point was not yet reached in the PRRT + CAP/TEM group. Moreover, the PRRT + CAP/TEM group showed a significantly higher reduction of SSTR-PET-based metabolic tumor volume and chromogranin A levels compared with the PRRT only group. Importantly, adverse events of all grades did not differ between both groups., Conclusions: PRRT + CAP/TEM represents a highly promising and well-tolerated therapeutic regimen for patients experiencing somatostatin receptor-positive NET with higher (Ki67 ≥ 15%) proliferation rate. Prospective randomized clinical trials are warranted., Competing Interests: Conflicts of interest and sources of funding: The authors declare that they have no competing interests. This work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation, Germany’s Excellence Strategy EXC 2180-390900677) and the Werner Siemens-Foundation. Graphical abstract was created with BioRender.com ., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The tumor-associated disialoganglioside GD2 is a bona fide immunotherapy target in neuroblastoma and other childhood tumors, including Ewing sarcoma and osteosarcoma. GD2-targeting antibodies proved to be effective in neuroblastoma and GD2-targeting chimeric antigen receptors (CAR)- expressing T cells as well as natural killer T cells (NKTs) are emerging. However, assessment of intra- and intertumoral heterogeneity has been complicated by ineffective immunohistochemistry as well as sampling bias in disseminated disease. Therefore, a non-invasive approach for the assessment and visualization of GD2 expression in-vivo is of upmost interest and might enable a more appropriate treatment stratification. Methods: Recently, [ 64 Cu]Cu-NOTA-ch14.18/CHO ( 64 Cu-GD2), a radiolabeled GD2-antibody for imaging with Positron-Emission-Tomography (PET) was developed. We here report our first clinical patients' series (n = 11) in different pediatric tumors assessed with 64 Cu-GD2 PET/MRI. GD2-expression in tumors and tissue uptake in organs was evaluated by semiquantitative measurements of standardized uptake values (SUV) with PET/MRI on day 1 p.i. (n = 11) as well as on day 2 p.i. (n = 6). Results: In 8 of 9 patients with suspicious tumor lesions on PET/MRI at least one metastasis showed an increased 64 Cu-GD2 uptake and a high tracer uptake (SUV max > 10) was measured in 4 of those 8 patients. Of note, sufficient image quality with high tumor to background contrast was readily achieved on day 1. In case of 64 Cu-GD2-positive lesions, an excellent tumor to background ratio (at least 6:1) was observed in bones, muscles or lungs, while lower tumor to background contrast was seen in the spleen, liver and kidneys. Furthermore, we demonstrated extensive tumor heterogeneity between patients as well as among different metastatic sites in individual patients. Dosimetry assessment revealed a whole-body dose of only 0.03 mGy/MBq (range 0.02-0.04). Conclusion: 64 Cu-GD2 PET/MRI enables the non-invasive assessment of individual heterogeneity of GD2 expression, which challenges our current clinical practice of patient selection, stratification and immunotherapy application scheme for treatment with anti-GD2 directed therapies., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

In oncology, intratumoural heterogeneity is closely linked with the efficacy of therapy, and can be partially characterized via tumour biopsies. Here we show that intratumoural heterogeneity can be characterized spatially via phenotype-specific, multi-view learning classifiers trained with data from dynamic positron emission tomography (PET) and multiparametric magnetic resonance imaging (MRI). Classifiers trained with PET-MRI data from mice with subcutaneous colon cancer quantified phenotypic changes resulting from an apoptosis-inducing targeted therapeutic and provided biologically relevant probability maps of tumour-tissue subtypes. When applied to retrospective PET-MRI data of patients with liver metastases from colorectal cancer, the trained classifiers characterized intratumoural tissue subregions in agreement with tumour histology. The spatial characterization of intratumoural heterogeneity in mice and patients via multimodal, multiparametric imaging aided by machine-learning may facilitate applications in precision oncology., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Molecular imaging has experienced enormous advancements in the areas of imaging technology, imaging probe and contrast development, and data quality, as well as machine learning-based data analysis. Positron emission tomography (PET) and its combination with computed tomography (CT) or magnetic resonance imaging (MRI) as a multimodality PET-CT or PET-MRI system offer a wealth of molecular, functional and morphological data with a single patient scan. Despite the recent technical advances and the availability of dozens of disease-specific contrast and imaging probes, only a few parameters, such as tumour size or the mean tracer uptake, are used for the evaluation of images in clinical practice. Multiparametric in vivo imaging data not only are highly quantitative but also can provide invaluable information about pathophysiology, receptor expression, metabolism, or morphological and functional features of tumours, such as pH, oxygenation or tissue density, as well as pharmacodynamic properties of drugs, to measure drug response with a contrast agent. It can further quantitatively map and spatially resolve the intertumoural and intratumoural heterogeneity, providing insights into tumour vulnerabilities for target-specific therapeutic interventions. Failure to exploit and integrate the full potential of such powerful imaging data may lead to a lost opportunity in which patients do not receive the best possible care. With the desire to implement personalized medicine in the cancer clinic, the full comprehensive diagnostic power of multiplexed imaging should be utilized., (© 2023. Springer Nature Limited.)

Aim/introduction: Peptide receptor radionuclide therapy (PRRT) is an effective and well-tolerated treatment option for patients with neuroendocrine tumors (NETs) that prolongs progression-free survival (PFS). However, the limited overall survival (OS) rates in the prospective phase III study (NETTER1) highlighted the need to identify patient-specific long-term prognostic markers to avoid unnecessary side effects and enable better treatment stratification. Therefore, we retrospectively analyzed prognostic risk factors in NET patients treated with PRRT., Methods: A total of 62 NET patients (G1: 33.9%, G2 62.9%, and G3 3.2%) with at least 2 cycles of PRRT with [ 177 Lu]Lu-HA-DOTATATE (mean 4 cycles) were analyzed. Of which, 53 patients had primary tumors in the gastroenteropancreatic (GEP) system, 6 had bronchopulmonary NET, and 3 had NET of unknown origin. [ 68 Ga]Ga-HA-DOTATATE PET/CT scans were performed before PRRT start and after the second treatment cycle. Different clinical laboratory parameters, as well as PET parameters, such as SUVmean, SUVmax, and PET-based molecular tumor volume (MTV), were collected, and their impact on the OS was investigated. Patient data with a mean follow-up of 62 months (range 20-105) were analyzed., Results: According to interim PET/CT, 16 patients (25.8%) presented with partial response (PR), 38 (61.2%) with stable disease (SD), and 7 (11.3%) with progressive disease (PD). The 5-year OS was 61.8% for all patients, while bronchopulmonary NETs showed poorer OS than GEP-NETs. Multivariable Cox regression analysis showed that chromogranin A level and MTV together were highly significant predictors of therapeutic outcome (HR 2.67; 95% CI 1.41-4.91; p = 0.002). Treatment response was also influenced by the LDH level (HR 0.98; 95% CI 0.9-1.0; p = 0.007) and patient age (HR 1.15; 95% CI 1.08-1.23; p < 0.001). ROC analysis revealed baseline MTV > 112.5 ml [Sens. 91%; Spec. 50%; AUC 0.67 (95% CI 0.51-0.84, p = 0.043)] and chromogranin A >1,250.75 μg/l [Sens. 87%; Spec. 56%; AUC 0.73 (95% CI 0.57-0.88, p = 0.009)] as the best cutoff values for identifying patients with worse 5-year survival., Conclusion: Our retrospective analysis defined MTV and chromogranin A in combination as significant prognostic factors for long-term OS. Furthermore, an interim PET/CT after two cycles has the potential in identifying non-responders who may benefit from a change in therapy at an early stage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Trautwein, Schwenck, Jacoby, Reischl, Fiz, Zender, Dittmann, Hinterleitner and la Fougère.)

Purpose: Resection of the tumor-draining lymph -node (TDLN) represents a standard method to identify metastasis for several malignancies. Interestingly, recent preclinical studies indicate that TDLN resection diminishes the efficacy of immune checkpoint inhibitor-based cancer immunotherapies. Thus, accurate preclinical identification of TDLNs is pivotal to uncovering the underlying immunological mechanisms. Therefore, we validated preclinically, and clinically available non-invasive in vivo imaging approaches for precise TDLN identification., Procedures: For visualization of the lymphatic drainage into the TDLNs by non-invasive in vivo optical imaging, we injected the optical imaging contrast agents Patent Blue V (582.7 g mol -1 ) and IRDye® 800CW polyethylene glycol (PEG; 25,000-60,000 g mol -1 ), subcutaneously (s.c.) in close proximity to MC38 adenocarcinomas at the right flank of experimental mice. For determination of the lymphatic drainage and the glucose metabolism in TDLNs by non-invasive in vivo PET/magnetic resonance imaging (PET/MRI), we injected the positron emission tomography (PET) tracer (2-deoxy-2[ 18 F]fluoro-D-glucose ( 18 F-FDG) [181.1 g mol -1 ]) in a similar manner. For ex vivo cross-correlation, we isolated TDLNs and contralateral nontumor-draining lymph nodes (NTDLNs) and performed optical imaging, biodistribution, and autoradiography analysis., Results: The clinically well-established Patent Blue V was superior for intraoperative macroscopic identification of the TDLNs compared with IRDye® 800CW PEG but was not sensitive enough for non-invasive in vivo detection by optical imaging. Ex vivo Patent Blue V biodistribution analysis clearly identified the right accessory axillary and the proper axillary lymph node (LN) as TDLNs, whereas ex vivo IRDye® 800CW PEG completely failed. In contrast, functional non-invasive in vivo 18 F-FDG PET/MRI identified a significantly elevated uptake exclusively within the ipsilateral accessory axillary TDLN of experimental mice and was able to differentiate between the accessory axillary and the proper LN. Ex vivo biodistribution and autoradiography confirmed our in vivo 18 F-FDG PET/MRI results., Conclusions: When taken together, our results demonstrate the feasibility of 18 F-FDG-PET/MRI as a valid method for non-invasive in vivo, intraoperative, and ex vivo identification of the lymphatic drainage and glucose metabolism within the TDLNs. In addition, using Patent Blue V provides additive value for the macroscopic localization of the lymphatic drainage both visually and by ex vivo optical imaging analysis. Thus, both methods are valuable, easy to implement, and cost-effective for preclinical identification of the TDLN., (© 2022. The Author(s).)

Aim/Introduction: Despite the spectacular success of immune checkpoint inhibitor therapy (ICT) in patients with metastatic cancer, only a limited proportion of patients benefit from ICT. CD8 + cytotoxic T cells are important gatekeepers for the therapeutic response to ICT and are able to recognize MHC class I-dependent tumor antigens and destroy tumor cells. The radiolabeled minibody [ 89 Zr]Zr-Df-IAB22M2C has a high affinity for human CD8 + T cells and was successfully tested in a phase I study. Here, we aimed to gain the first clinical PET/MRI experience with the noninvasive assessment of the CD8 + T-cell distribution in cancer patients by in vivo [ 89 Zr]Zr-Df-IAB22M2C with a distinct focus of identifying potential signatures of successful ICT. Material and Methods: We investigated 8 patients with metastasized cancers undergoing ICT. Radiolabeling of Df-IAB22M2C with Zr-89 was performed according to Good Manufacturing Practice. Multiparametric PET/MRI was acquired 24 h after injection of 74.2±17.9 MBq [ 89 Zr]Zr-Df-IAB22M2C. We analyzed [ 89 Zr]Zr-Df-IAB22M2C uptake within the metastases and within primary and secondary lymphatic organs. Results: [ 89 Zr]Zr-Df-IAB22M2C injection was tolerated well without noticeable side effects. The CD8 PET/MRI data acquisitions 24 hours post-administration of [ 89 Zr]Zr-Df-IAB22M2C revealed good image quality with a relatively low background signal due to only low unspecific tissue uptake and marginal blood pool retention. Only two metastatic lesions showed markedly increased tracer uptake in our cohort of patients. Furthermore, we observed high interpatient variability in [ 89 Zr]Zr-Df-IAB22M2C uptake within the primary and secondary lymphoid organs. Four out of five ICT patients exhibited rather high [ 89 Zr]Zr-Df-IAB22M2C uptake in the bone marrow. Two of these four patients as well as two other patients yielded pronounced [ 89 Zr]Zr-Df-IAB22M2C uptake within nonmetastatic lymph nodes. Interestingly, cancer progression in ICT patients was associated with a relatively low [ 89 Zr]Zr-Df-IAB22M2C uptake in the spleen compared to the liver in 4 out of the 6 patients. Lymph nodes with enhanced [ 89 Zr]Zr-Df-IAB22M2C uptake revealed significantly reduced apparent diffusion coefficient (ADC) values in diffusion weighted MRI. Conclusion: Our first clinical experiences revealed the feasibility of [ 89 Zr]Zr-Df-IAB22M2C PET/MRI in assessing potential immune-related changes in metastases and primary and secondary lymphatic organs. According to our results, we hypothesize that alterations in [ 89 Zr]Zr-Df-IAB22M2C uptake in primary and secondary lymphoid organs might be associated with the response to ICT., Competing Interests: Competing Interests: R.K. and I.W. are employees of ImaginAB. ClF is an advisor of ImaginAB. The other authors report no conflicts of interest., (© The author(s).)

Despite the world-wide prevalence of hypertension, there is a lack in open-source software for analyzing blood pressure data. The R package bp fills this gap by providing functionality for blood pressure data processing, visualization, and feature extraction. In addition to the comprehensive functionality, the package includes six sample data sets covering continuous arterial pressure data (AP), home blood pressure monitoring data (HBPM) and ambulatory blood pressure monitoring data (ABPM), making it easier for researchers to get started. The R package bp is publicly available on CRAN and at https://github.com/johnschwenck/bp., Competing Interests: The authors have declared that no competing interests exist.

The detection of occult infections and low-grade inflammation in clinical practice remains challenging and much depending on readers' expertise. Although molecular imaging, like [ 18 F]FDG PET or radiolabeled leukocyte scintigraphy, offers quantitative and reproducible whole body data on inflammatory responses its interpretation is limited to visual analysis. This often leads to delayed diagnosis and treatment, as well as untapped areas of potential application. Artificial intelligence (AI) offers innovative approaches to mine the wealth of imaging data and has led to disruptive breakthroughs in other medical domains already. Here, we discuss how AI-based tools can improve the detection sensitivity of molecular imaging in infection and inflammation but also how AI might push the data analysis beyond current application toward predicting outcome and long-term risk assessment., (© 2022. The Author(s).)

Background: Antibodies targeting surface expressed disialoganglioside GD2 are increasingly used in neuroblastoma immunotherapy and might also have potential for use in radioimmunotherapy. As such targeted treatments might benefit from a dedicated theranostic approach, we studied the influence of radiolabeling on the binding characteristics of ch14.18 antibodies produced by Chinese hamster ovary (CHO) cells and evaluated the benefit of GD2-ImmunoPET as a potential tool for therapy planning. Methods: 64 Cu was used to reduce radiation burden, which is of high importance especially in a pediatric patient population. 64 Cu-labeling was accomplished using the chelators NOTA- or DOTAGA-NCS. Radiolabeled antibodies were characterized in vitro . [ 64 Cu]Cu-DOTAGA-ch14.18/CHO was studied in a neuroblastoma mouse model (subcutaneous CHP-134 xenografts). In vivo PET and MR images were acquired at 3 h, 24 h, and 48 h p.i. The specificity of binding was verified using GD2-negative tumors (HEK-293 xenografts), a control antibody and in vivo blocking. A first translational application was performed by PET/MRI in a patient with metastasized neuroblastoma. Results: Radiolabeling at an antibody-to-chelator ratio ≥1:10 yielded a product with a radiochemical purity of ≥90% and a specific activity of 0.2-1.0 MBq/µg. Radiochelation was stable over 48 h in PBS, mouse serum or EDTA, and 50.8 ± 3.5% and 50.8 ± 2.0% of the radiolabeled conjugates, prepared at antibody-to-chelator ratios of 1:10 or 1:15, were immunoreactive. In vivo, highly specific accumulation (31.6 ± 5.8% ID/g) in neuroblastoma was shown preclinically. Clinical PET/MR scans using [ 64 Cu]Cu-NOTA-ch14.18/CHO (NOTA used for safety reasons) could visualize neuroblastoma metastases. Conclusions: In vivo, 64 Cu-labeled ch14.18/CHO is suitable for specific identification of neuroblastoma in PET. A first patient PET indicated the feasibility of the method for clinical translation and the potential utility in image-guided therapy., Competing Interests: Competing Interests: J.S. is now an employee of Boehringer-Ingelheim Pharma GmbH & Co. KG, the work was part of her PhD thesis at the University of Tuebingen. J.F.S receives grant/research support from: Siemens, and Bayer Healthcare; however, none of the grants are directly related to this work. C.l.F. receives grant/research support from: Oncovision, GE, and Siemens; however, none of the grants are directly related to this work. B.J.P. receives grant/research support from: Bayer Healthcare, Boehringer-Ingelheim, ImaginAb, Oncodesign, Bruker, and Siemens; however, none of the grants are directly related to this work. M.P. is now employee of Foundation Medicine, the work was part of his Master's Thesis at the University of Tuebingen. S.D.G. is an employee of Provenance Biopharmaceuticals Corp. No conflicts of interest to disclose: A.M., G.R., M.A.K, D.S., J. Schw., J.E.W, R.H, L.Q.-M, (© The author(s).)

Background: Meniscal injury is one of the most common indications for knee surgery. The advent of meniscal repair techniques has facilitated meniscal preservation in suitable cases. Meniscal substitution with scaffolds may be advantageous following partial meniscal resection. There are three main scaffolds in current clinical use; Collagen Meniscal Implant (CMI Stryker Corporation, Kalamazoo, MI, USA), Actifit (Actifit, Orteq Ltd, London, UK) and NUsurface (Active Implants, LLC). The purpose of this systematic review was to compare clinical outcomes and failure rates of patients who have had implantation with these meniscal scaffolds., Methods: MEDLINE and EMBASE databases were searched for studies that included patients who had surgical implantation with Actifit or CMI. Eligibility criteria included papers that described both clinical outcomes and failure rates of these implants, a mean follow up of 5 years and studies published in English. A Google search was also performed to identify any grey literature., Results: Five Level IV studies were found for Actifit. One Level II, one Level III and four Level IV studies were found for the CMI implant. One Level II study was identified for the NUsurface scaffold with a follow-up 12 months and was included for completeness. Overall, 262 patients were treated with Actifit, 109 with CMI and 65 with NUsurface. Failure rates for Actifit were 18% (range 6.3-31.8%) with a mean follow up of 66.8 months, and for CMI 6.5% (range 0-11.8%) with a mean follow up of 97.1 months. The NUsurface failure rate was 16.9% at 12 months. Clinical outcomes such as VAS, Tegner and Lysholm scores improved significantly post-operatively. However, there was a high volume of concurrent procedures, such as anterior cruciate ligament reconstructions and high tibial osteotomies in each study group; 118 (45%) for Actifit and 53 (45%) for CMI., Conclusion: The evidence for meniscal scaffold use is insufficient to suggest that they could potentially improve clinical outcomes in patients post-meniscal resection. This is largely due to the high proportion of concurrent procedures performed at index procedure for both CMI and Actifit. On the basis of current evidence, the use of meniscal scaffolds as a sole treatment for partial meniscal defects cannot be recommended, owing to the relatively high failure rate and paucity of clinical data., (© 2022. The Author(s).)

Objectives: To examine the numbers and patterns of patients presenting to an urban acute general hospital with acute mental health presentations and to further investigate any variation related to the COVID-19 pandemic., Design: Retrospective observational cohort study., Setting: An urban acute general hospital in London, UK, comprising of five sites and two emergency departments. The hospital provides tertiary level general acute care but is not an acute mental health services provider. There is an inpatient liaison psychiatry service., Participants: 358 131 patients attended the emergency departments of our acute general hospital during the study period. Of these, 14 871 patients attended with an acute mental health presentation. A further 14 947 patients attending with a physical illness were also noted to have a concurrent recorded mental health diagnosis., Results: Large numbers of patients present to our acute general hospital with mental health illness even though the organisation does not provide mental health services other than inpatient liaison psychiatry. There was some variation in the numbers and patterns of presentations related to the COVID-19 pandemic. Patient numbers reduced to a mean of 9.13 (SD 3.38) patients presenting per day during the first 'lockdown' compared with 10.75 (SD 1.96) patients per day in an earlier matched time period (t=3.80, p<0.01). Acute mental health presentations following the third lockdown increased to a mean of 13.84 a day., Conclusions: Large numbers of patients present to our acute general hospital with mental health illness. This suggests a need for appropriate resource, staffing and training to address the needs of these patients in a non-mental health provider organisation and subsequent appropriate transfer for timely treatment. The COVID-19 pandemic and the resulting lockdowns have resulted in variation in the numbers and patterns of patients presenting with acute mental health illness but these presentations are not new. Considerable work is still needed to provide integrated care which addresses the physical and mental healthcare needs of patients presenting to acute and general hospitals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Abstract: Incidental findings of thyroid lesions, some of which show increased FDG uptake, are common in whole-body FDG PET/CT imaging of oncological patients. As metastases to the thyroid are extremely rare, it is often a matter of debate, whether thyroid lesions should be considered as benign goiter or evaluated further. Here, we present the case of a 65-year-old woman with history of small cell lung cancer and multiple thyroid lesions, classified as benign nodular goiter. Because in restating using 18F-FDG PET/CT these lesions showed an increased FDG uptake and growth progression, decision was made for fine-needle aspiration, which revealed small cell lung cancer metastasis 14 months after first tumor diagnosis., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background We undertook a prospective qualitative study to ascertain the perceptions and experience of trainee doctors in the first two years of formal core surgical training related to patient safety improvement and incident reporting. We sought to explore the beliefs, knowledge and opinions of core surgical trainees related to patient safety improvement, their understanding of existing patient safety initiatives and their experience and attitudes to incident reporting. Methods We identified 1133 doctors in formal core surgical training posts in the United Kingdom at this time, and we contacted these doctors to invite them to participate in our study. We received responses from 687 (60.6%) core surgical trainees, and 612 trainees (54%) agreed to participate. The study participants underwent an interview using structured questions asked by trained assessors with an opportunity to explore any particular themes identified by the trainee in more detail. Qualitative data related to the knowledge, experience and perceptions of safety improvement and incident reporting were collected. Results Overall, 163 surgical trainees (26.6%) reported that they felt that they could impact patient safety positively. A total of 222 trainees (36.3%) had been involved in or witnessed an adverse patient safety event, while 509 trainees (83.2%) reported that they had witnessed a 'near-miss' event. Only 81 trainees (13.2%) had submitted a patient safety report at some point in their career. In addition, 536 trainees (87.6%) reported that they considered a patient safety or incident report to be 'negative' or 'seriously negative' and that they would be discouraged from making these because of the negative connotations associated with them. Of the 81 core surgical trainees who had submitted a patient safety report, only nine trainees (11.1%) reported that they had received a meaningful reply and update following their report. Several themes were identified during the interviews in response to open questions. These included a perception that patient safety improvement is the responsibility of senior surgeons and managers and that surgical trainees did not feel empowered to influence patient safety improvement. Trainees expressed the view that incident reporting reflected negatively on clinicians and the standard of care provided, and there were reports of culture based on blame and the fear of litigation or complaints. Surgical trainees did not feel that incident reporting was an effective tool for patient safety improvement, and those trainees who had made patient safety reports felt that these did not result in change and that they often received no feedback. Conclusions Core surgical trainees report that they are not well engaged in patient safety improvement and that their perceptions and experience of incident reporting are not positive. This represents a missed opportunity. We suggest that in order to recruit the surgical workforce to the improvement work and learning associated with patient safety, opportunities for focused education, training and culture change are needed from the early years of surgical training. In addition, improvements to the processes and systems that allow trainees to engage with safety improvement are needed in order to make these more user-friendly and accessible., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Jeffrey et al.)