Patients presenting to an acute general hospital with acute mental health needs. A retrospective observational cohort study

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

A role for artificial intelligence in molecular imaging of infection and inflammation

The detection of occult infections and low-grade inflammation in clinical practice remains challenging and much depending on readers' expertise. Although molecular imaging, like [F-18]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

Cancer immunotherapy is accompanied by distinct metabolic patterns in primary and secondary lymphoid organs observed by non-invasive in vivo18F-FDG-PET

Purpose: Cancer immunotherapy depends on a systemic immune response, but the basic underlying mechanisms are still largely unknown. Despite the very successful and widespread use of checkpoint inhibitors in the clinic, the majority of cancer patients do not benefit from this type of treatment. In this translational study, we investigated whether noninvasive in vivo positron emission tomography (PET) imaging using 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) is capable of detecting immunotherapy-associated metabolic changes in the primary and secondary lymphoid organs and whether this detection enables the prediction of a successful anti-cancer immune response. Methods: RIP1-Tag2 mice with progressed endogenous insular cell carcinomas underwent a combined cancer immunotherapy consisting of CD4+ T cells plus monoclonal antibodies (mAbs) against programmed death ligand-1 (PD-L1) and lymphocyte activation gene-3 (LAG-3) or a sham treatment after radiation-mediated immune cell depletion. A second cohort of RIP1-Tag2 mice underwent exclusive checkpoint inhibitor therapy (CIT) using anti-PD-L1/LAG-3 mAbs or sham treatment without initial immune cell depletion to mimic the clinical situation. All mice were monitored by 18F-FDG-PET combined with anatomical magnetic resonance imaging (MRI). In addition, we retrospectively analyzed PET / computed tomography (CT) scans (PET/CT) regarding 18F-FDG uptake of CIT-treated metastatic melanoma patients in the spleen (n=23) and bone marrow (BM; n=20) as well as blood parameters (n=17-21). Results: RIP1-Tag2 mice with advanced insular cell carcinomas treated with combination immunotherapy exhibited significantly increased 18F-FDG uptake in the spleen compared to sham-treated mice. Histopathology of the spleens from treated mice revealed atrophy of the white pulp with fewer germinal centers and an expanded red pulp with hyperplasia of neutrophils than those of sham-treated mice. Immunohistochemistry and flow cytometry analyses of the spleens revealed a lower number of T cells and a higher number of neutrophils compared to those in the spleens of sham-treated mice. Flow cytometry of the BM showed enhanced activation of T cells following the treatment schemes that included checkpoint inhibitors. The ratio of 18F-FDG uptake at baseline to the uptake at follow-up in the spleens of exclusively CIT-treated RIP1-Tag2 mice was significantly enhanced, but the ratio was not enhanced in the spleens of the sham-treated littermates. Flow cytometry analysis confirmed a reduced number of T cells in the spleens of exclusively CIT-treated mice compared to that of sham-treated mice. A retrospective analysis of clinical 18F-FDG-PET/CT scans revealed enhanced 18F-FDG uptake in the spleens of some successfully CIT-treated patients with metastatic melanoma, but there were no significant differences between responders and non-responders. The analysis of the BM in clinical 18F-FDG-PET/CT scans with a computational segmentation tool revealed significantly higher baseline 18F-FDG uptake in patients who responded to CIT than in non-responders, and this relationship was independent of bone metastasis, even in the baseline scan. Conclusions: Thus, we are presenting the first translational study of solid tumors focusing on the metabolic patterns of primary and secondary lymphoid organs induced by the systemic immune response after CIT. We demonstrate that the widely available 18F-FDG-PET modality is an applicable translational tool that has high potential to stratify patients at an early time point

Preparation and in vitro evaluation of 177Lu-iPSMA-RGD as a new heterobivalent radiopharmaceutical

This study aimed to synthesize a new 177Lu-iPSMA-RGD heterobivalent radiopharmaceutical, as well as to assess the in vitro radiopharmaceutical potential to target cancer cells overexpressing PSMA and a(v) b(3) integrins. The radiotracer prepared with a radiochemical purity of 98.8 ± 1.0% showed stability in human serum, specific recognition with suitable affinity to PSMA and a(v)b(3) integrins, and capability to inhibit cancer cell proliferation and VEGF signaling (antiangiogenic effect). Results warrant further preclinical studies to establish the 177Lu-iPSMA-RGD potential as a dual therapeutic radiopharmaceutical.CONACyT-CB-2016-01-28152

Parent-reported and clinician-observed autism spectrum disorder (ASD) symptoms in children with attention deficit/hyperactivity disorder (ADHD): implications for practice under DSM-5

BACKGROUND: Children with attention deficit/hyperactivity disorder (ADHD) often present with social difficulties, though the extent to which these clearly overlap with symptoms of autism spectrum disorder (ASD) is not well understood. METHODS: We explored parent-reported and directly-observed ASD symptoms on the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS) in children referred to ASD-specialty clinics who received diagnoses of either ADHD (n = 48) or ASD (n = 164). RESULTS: Of the ADHD sample, 21 % met ASD cut-offs on the ADOS and 30 % met ASD cut-offs on all domains of the ADI-R. Four social communication ADOS items (Quality of Social Overtures, Unusual Eye Contact, Facial Expressions Directed to Examiner, and Amount of Reciprocal Social Communication) adequately differentiated the groups while none of the items on the ADI-R met the criteria for adequate discrimination. CONCLUSIONS: Results of this work highlight the challenges that clinicians and researchers face when distinguishing ASD from other disorders in verbally fluent, school-age children

Viral community analysis in a marine oxygen minimum zone indicates increased potential for viral manipulation of microbial physiological state.

Microbial communities in oxygen minimum zones (OMZs) are known to have significant impacts on global biogeochemical cycles, but viral influence on microbial processes in these regions are much less studied. Here we provide baseline ecological patterns using microscopy and viral metagenomics from the Eastern Tropical North Pacific (ETNP) OMZ region that enhance our understanding of viruses in these climate-critical systems. While extracellular viral abundance decreased below the oxycline, viral diversity and lytic infection frequency remained high within the OMZ, demonstrating that viral influences on microbial communities were still substantial without the detectable presence of oxygen. Viral community composition was strongly related to oxygen concentration, with viral populations in low-oxygen portions of the water column being distinct from their surface layer counterparts. However, this divergence was not accompanied by the expected differences in viral-encoded auxiliary metabolic genes (AMGs) relating to nitrogen and sulfur metabolisms that are known to be performed by microbial communities in these low-oxygen and anoxic regions. Instead, several abundant AMGs were identified in the oxycline and OMZ that may modulate host responses to low-oxygen stress. We hypothesize that this is due to selection for viral-encoded genes that influence host survivability rather than modulating host metabolic reactions within the ETNP OMZ. Together, this study shows that viruses are not only diverse throughout the water column in the ETNP, including the OMZ, but their infection of microorganisms has the potential to alter host physiological state within these biogeochemically important regions of the ocean

Preclinical Identification Of Tumor-Draining Lymph Nodes Using a Multimodal Non-invasive In vivo Imaging Approach

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[18F]fluoro-D-glucose (18F-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 vivo18F-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 vivo18F-FDG PET/MRI results. Conclusions: When taken together, our results demonstrate the feasibility of 18F-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