Additional Clinical Information Research Articles

Change in Emergency Department Length of Stay Following Routine Adoption of Dual-Energy Computed Tomography to Differentiate Intracranial Hemorrhage from Calcification.

Dual energy computed tomography (DECT) is an advanced CT technique which has been shown to improve accuracy in distinguishing between intracranial hemorrhage and calcification, which is often challenging on conventional CT and therefore may warrant repeat imaging in the emergency department (ED) to document stability and exclude enlarging intracranial hemorrhage. We hypothesized that implementation of a DECT head protocol with fully automated post processing in the ED would decrease the need for repeat imaging and therefore reduce overall ED length of stay (LOS). This is a retrospective study comparing ED length of stay over a one-year period before (7/1/2016-6/30/2017) and after (7/1/2018-6/30/2019) implementing a DECT head protocol, for patients scanned for headache, trauma or fall, who were found to have indeterminate intracranial hyperdensities on conventional images, and were subsequently discharged home from the ER (excluding patients who were admitted, taken to the OR, or left against medical advice). Additional clinical information regarding ED time course and management were also reviewed, including data on time to CT scan, CT report, and if applicable, time to repeat CT head and neurosurgical consultation. There was no significant difference in patient demographics and CT indications between the pre-DECT and post-DECT cohorts. There was a small but statistically significant difference in mean baseline ED LOS in the initial cohorts of 20 minutes (p=0.002). After the inclusion of only intracranial indeterminate hyperdensities, there was a larger statistically significant difference in ED LOS, with mean pre-DECT LOS of 421 minutes and mean post-DECT LOS of 272 mins, resulting in mean LOS reduction of 149 mins (p=0.003). The increased ED LOS correlated with increased frequency of neurosurgical consultation and repeat CT head for the findings of indeterminate intracranial hyperdensities. ED LOS was significantly longer in the pre-DECT cohort, which was partly attributable to neurosurgical consultation and repeat CT head performed for indeterminate intracranial hyperdensities. DECT＝ Dual Energy CT; ED LOS＝ Emergency department length of stay; NECT = Noncontrast enhanced CT; VNCa= Virtual non-calcium.

Using RET-He and Delta-He in the Sysmex XN-1000V Analyzer to Differentiate Between Chronic Hemorrhagic and Chronic Inflammatory Anemia in Small Animals.

Chronic hemorrhagic anemia (CHA) and anemia of chronic inflammation (ACI) are difficult to differentiate in small animals using hematology. Advanced hematological parameters (RET-He, Delta-He and %Hypo-He) are used in humans to discriminate between types of non-regenerative anemia. Whether they could be useful in the diagnosis of CHA and ACI in small animals is unknown. We evaluated these parameters in the Sysmex XN-1000V analyzer in a population of non-anemic and anemic dogs and cats. Delta-He was significantly different between dogs with CHA and ACI. Moreover, Delta-He and RET-He were different between healthy and non-anemic dogs with inflammation. Neither of these two statements was true for cats. We also report the reference ranges for these parameters using the Sysmex XN-1000V. Although additional clinical and laboratory information should always be considered, the measurement of these parameters using this analyzer can help clinicians to classify type of anemia.

Revolution or risk?-Assessing the potential and challenges of GPT-4V in radiologic image interpretation.

ChatGPT-4 Vision (GPT-4V) is a state-of-the-art multimodal large language model (LLM) that may be queried using images. We aimed to evaluate the tool's diagnostic performance when autonomously assessing clinical imaging studies. A total of 206 imaging studies (i.e., radiography (n = 60), CT (n = 60), MRI (n = 60), and angiography (n = 26)) with unequivocal findings and established reference diagnoses from the radiologic practice of a large university hospital were accessed. Readings were performed uncontextualized, with only the image provided, and contextualized, with additional clinical and demographic information. Responses were assessed along multiple diagnostic dimensions and analyzed using appropriate statistical tests. With its pronounced propensity to favor context over image information, the tool's diagnostic accuracy improved from 8.3% (uncontextualized) to 29.1% (contextualized, first diagnosis correct) and 63.6% (contextualized, correct diagnosis among differential diagnoses) (p ≤ 0.001, Cochran's Q test). Diagnostic accuracy declined by up to 30% when 20 images were re-read after 30 and 90 days and seemed unrelated to the tool's self-reported confidence (Spearman's ρ = 0.117 (p = 0.776)). While the described imaging findings matched the suggested diagnoses in 92.7%, indicating valid diagnostic reasoning, the tool fabricated 258 imaging findings in 412 responses and misidentified imaging modalities or anatomic regions in 65 images. GPT-4V, in its current form, cannot reliably interpret radiologic images. Its tendency to disregard the image, fabricate findings, and misidentify details, especially without clinical context, may misguide healthcare providers and put patients at risk. Question Can Generative Pre-trained Transformer 4 Vision (GPT-4V) interpret radiologic images-with and without clinical context? Findings GPT-4V performed poorly, demonstrating diagnostic accuracy rates of 8% (uncontextualized), 29% (contextualized, most likely diagnosis correct), and 64% (contextualized, correct diagnosis among differential diagnoses). Clinical relevance The utility of commercial multimodal large language models, such as GPT-4V, in radiologic practice is limited. Without clinical context, diagnostic errors and fabricated findings may compromise patient safety and misguide clinical decision-making. These models must be further refined to be beneficial.

7756 Gonadectomy in Individuals with Differences of Sex Development - A Prospective I-DSD Registry Study

Abstract Disclosure: M.A. O'Connell: None. A.K. Lucas-Herald: None. J. Bryce: None. M. Chen: None. J.H. Davies: None. M. Shnorhavorian: None. N. Atapattu: None. I. Bachynska: None. N. Birkebaek: None. M. Cools: None. K. Demir: None. L. de Vries: None. H. Elsedfy: None. M.A. Fahmy: None. E. Globa: None. R. Grinspon: None. G. Guaragna-Filho: None. G. Guerra-Junior: None. D. Janus: None. Z. Kolesinska: None. I. Mazen: None. S.M. O'Connell: None. S.N. Seneviratne: None. M. Stancampiano: None. G. Verkauskas: None. S.F. Ahmed: None. O. i-DSD gonadectomy surveillance consortium: None. Introduction: Gonadectomy may be indicated in people with differences of sex development (DSD), but variation in practice is reported. This study aims to determine, through prospective surveillance, the frequency of gonadectomy and associated care pathways in individuals with DSD internationally. Methods: All I-DSD centres were invited to participate; the study commenced in December 2022. Participating centres receive a monthly email asking whether a gonadectomy has been performed in an individual with DSD. Where informed consent for inclusion in the I-DSD Registry has been obtained in a reported case, a secondary survey captures additional clinical information. Results: Of 208 centres invited, 74 have responded to monthly email surveys. Over the first 12 months of surveillance, gonadectomies were reported in 71 individuals from 34 centres in 19 countries (median [range]: 1[1, 5]); 40 centres reported no gonadectomy. Secondary survey data are available for 30/65 (46%) of reported cases to date. Twenty-four (80%) individuals are female; median (range) age at gonadectomy was 9.2 (2.1,20.0) years. All had specialist multidisciplinary team involvement prior to gonadectomy: endocrinology (97%), genetics (77%) and psychology (67%) were most frequently involved. Gonads were intra-abdominal in 25/30 (83%). Differences of gonadal development (13/30 [43%]) and Turner syndrome (8/30 [27%]) were the most frequent underlying DSD. Pre-gonadectomy investigations included: hormonal testing (28/30 [93%]), imaging (23/30 [77%] - US alone n=14; US + MRI n=7; MRI alone n=2), direct visualisation at laparoscopy (7/30 [23%]) and gonadal biopsy (2/30 [7%]). Bilateral gonadectomy was undertaken in 25/30 (83%). Mitigation of future malignancy risk in the context of gonadal insufficiency was the most common primary indication for gonadectomy (19/30, [63%]); additional indications were concerning changes on biopsy/imaging (3/30 [10%]), hormone production incongruent with sex assigned (4/30 [13%]) or gender identity (2/30 [7%]) and parental choice (2/30 [7%]). Histopathology confirmed neoplastic change in 7 individuals (23%). Gonadectomy was intentionally deferred in 8/30 (27%) individuals, most commonly to allow their involvement in decision making. Twelve individuals (40%) were 12yrs or older at gonadectomy; all were involved in the pre-operative decision-making process. Conclusions: This study offers important contemporary insights into the practice of gonadectomy in individuals with DSD internationally. Multidisciplinary care provision prior to gonadectomy is standard; however, management pathways vary, likely reflecting diversity of clinical presentations and lack of consensus regarding optimal approach. The I-DSD platform shows clear utility for performing prospective surveillance of rare procedures; such studies are essential for care quality improvement. Presentation: 6/2/2024

Evaluating the predictive efficacy of real-time 3D echocardiography in cardiac resynchronization therapy

BackgroundThe aim of this study is to assess the predictive efficacy of real-time three-dimensional echocardiography (RT-3DE) and QRS wave duration in determining the response to cardiac resynchronization therapy (CRT) and assessing left ventricular systolic function pre- and post-CRT device implantation.MethodA total of 51 patients with heart failure undergoing CRT at the Second Affiliated Hospital of Nantong University between January 1, 2013, and October 31, 2020, were enrolled in this study. Traditional two-dimensional echocardiography and RT-3DE were performed pre and post-CRT, with QRS wave width data from electrocardiograms and additional clinical information collected. Patients were categorized into CRT responder (n = 36) and CRT non-responder (n = 15) groups based on their response to CRT device implantation. Comparative analyses were conducted on the general characteristics of both groups, as well as the predictive efficacy of RT-3DE and QRS wave width for CRT responsiveness and left ventricular systolic function. Data on the standard deviation (Tmsv16-SD, Tmsv12-SD, Tmsv6-SD) and maximum difference (Tmsv16-Dif, Tmsv12-Dif, Tmsv6-Dif) of left ventricular end-systolic volume (LVESV) at segments 16, 12, and 6, as well as QRS wave width, were collected and analyzed.ResultsThe indicators Tmsv6-Dif, Tmsv12-Dif, Tmsv16-Dif, Tmsv6-SD, Tmsv12-SD, Tmsv16-SD, and QRS wave width exhibited significantly higher values in the CRT responder group when compared to the CRT non-responder group (P < 0.05). Among these, Tmsv16-SD demonstrated superior predictive performance for post-CRT response, with a sensitivity of 88.9%, specificity of 80.0%, and a diagnostic cut-off value of 6.19%. This predictive capability exceeded that of the conventional indicator, QRS wave width.ConclusionRT-3DE enables accurate prediction of post-CRT patient response and significantly facilitates quantitative assessment of CRT therapy efficacy.

Study protocol for Early Tracking of Childhood Health determinants (ETCHED): A longitudinal observational life course study

BackgroundThe prevalence of childhood obesity and diabetes continues to rise in the United States (US), especially among minority populations. The objective of the Early Tracking of Childhood Health Determinants (ETCHED) study is to investigate the role of adverse fetal and early-life risk exposures that contribute to the development of childhood obesity and metabolic risk.MethodsETCHED is a longitudinal observational study of American Indian/Alaska Native (AI/AN) and Hispanic pregnant woman and their offspring. Pregnant mothers ≥ 18 years old are enrolled at a large public hospital system in the southwestern US. Enrolled mothers are followed through pregnancy, delivery, and the maternal/offspring dyad will be followed until the child’s 18th birthday. At each maternal visit, questionnaires assessing medical history, diet, physical activity, sleep, perceived stress, and socioeconomic and sociocultural information are obtained. Standard laboratory tests during maternal visits include glycemic measures, lipids, and renal function. Additional bio samples obtained include venous blood samples and cord blood for obesity/metabolic biomarkers and genetic/epigenetic testing, urinalysis, placental tissue for examining functional pathways, breast milk for metabolomics, and stool for metabolites and microbiome analysis. The offspring will have 6 infant/toddler visits at 6–12 weeks, 4 months, 6 months, 18 months, 2 and 3 years respectively. Thereafter, they will undergo comprehensive research visits (major visits) at 4–5 years, 6–9 years, 10–13 years, and 14–17 years. The major visits in children include detailed medical history, anthropometry, developmental assessment, socioeconomic and environmental assessments (food insecurity, family structure, and childcare), feeding and activity, biochemical tests, genetics/epigenetic testing, and ultrasound elastography. Electronic health records will be reviewed for additional clinical information. The primary analysis will constitute estimation of correlation coefficients between continuous variables. The planned study duration in this ongoing study is 23-years.DiscussionThis is a life course study that that will examine biological and environmental risk factors for obesity and cardiometabolic risk from the intrauterine period to early childhood and adolescence in a population with high-risk of obesity and type 2 diabetes in the United States. The ETCHED study would also provide a unique opportunity to combine multi-omics and clinical data to create novel integrative models to predict the cardiometabolic risk associated with childhood obesity and possibly identify etiopathogenetic mechanisms and future targets of intervention.Trial registration numberClinicalTrials.gov identifier: NCT03481829. Updated July 19, 2024, https://clinicaltrials.gov/study/NCT03481829?cond=ETCHED&rank=1.

Factors Influencing Time From Diagnosis to Treatment of Breast Cancer and the Impact of Longer Waiting Time on Survival in Kathmandu Valley, Nepal: A Population-Based Study.

Longer time between breast cancer (BC) diagnosis and treatment initiation is associated with poorer survival, and this may be a factor behind disparities in global survival rates. We assessed time to BC treatment in the Kathmandu Valley, Nepal, including factors associated with longer waiting times and their impact on survival. We conducted a retrospective population-based study of BC cases recorded in the Kathmandu Valley Population-Based Cancer Registry between 2018 and 2019. Fieldwork survey through telephone was undertaken to collect additional sociodemographic and clinical information. Logistic regression was performed to identify factors associated with longer time to treatment, and Kaplan-Meier and Cox proportional hazard regression was used to examine survival time and evaluate the association between longer time to treatment and survival. Among the 385 patients with BC, one third waited >4 weeks from diagnosis to initial treatment. Lower education was associated with longer time to treatment (adjusted odds ratio, 1.63 [95% CI, 1.03 to 2.60]). The overall 3-year survival rate was 88.6% and survival was not associated with time to treatment (P = .50). However, advanced stage at diagnosis was associated with poorer survival (adjusted hazard ratio, 4.09 [95% CI, 1.27 to 13.23]). There was some indication that longer time to treatment was associated with poorer survival for advanced-stage patients, but data quality limited that analysis. In the Kathmandu Valley, Nepal, women with a lower education tend to wait longer from BC diagnosis to treatment. Patients with advanced-stage BC had poorer survival, and longer waiting time may be associated with poorer survival for women diagnosed with advanced-stage disease.

Infectious mononucleosis complicated by transitory Epstein-Barr virus infection of T and natural killer cells

Epstein-Barr virus (EBV) typically infects B cells in infectious mononucleosis (IM), but a rare case shows EBV infection in T cells. Seven cases of lymphoproliferative disorder caused by EBV-positive cytotoxic T/natural killer (NK) cell proliferation in the lymph nodes, termed IM with transient EBV infection of T and NK cells (EBV + T/NK cells in IM), are reported here. The purpose of the study is to describe clinicopathological features of EBV + T/natural killer (NK) cells in IM of the lymph node. We retrospectively analysed seven cases of Chinese children and young people adults with EBV + T/NK cells in IM. We used morphological observation, immunohistochemical staining, EB virus in situ hybridisation detection, and analysis of T-cell receptor gene rearrangement. The patients were healthy prior to illness, experiencing sudden onset occurring in all the patients, with high fever as the first symptom, followed by lymphadenopathy and hepatosplenomegaly. Diagnosis occurred < 1.5 months of symptom onset. Most lymphocytes in lesions expressed CD3 and Granzyme B or TIA-1 and lacked CD5. CD56 was expressed in numerous cells in 5 of the 7 cases. EBV-encoded RNA (EBER) was detected in medium-to-large-sized cells (50–100 cells per cell/high-power field). T-cell receptor (TCR) gene rearrangement was seen in six cases, with monoclonal rearrangement in four cases. Treatment was conservative treatment but not chemotherapy. Four received anti-HLH therapy and others anti-inflammatory treatment. All patients survived with relapse after long-term clinical observation and follow-up. EBV + T/NK cells in IM can elicit malignant features that mimic T/NK-cell lymphoma pathologically and benign features mimicking IM clinically. These findings indicate that EBV + T/NK cells in IM could serve as valuable diagnosis. Additional clinical information, including age of onset (children and young people), nature of onset (sudden), disease course (short), symptoms (systemic), EBV infection status (acute), and lymph node involvement, is crucial for accurate diagnosis and prognostic evaluation.

Diagnostic yield of percutaneous, ultrasound-guided, fine needle aspirates of the gastrointestinal wall: a retrospective analysis of 152 samples.

The aim was to assess the technical success of percutaneous ultrasound-guided fine needle aspirates of gastrointestinal wall lesions and evaluate predictors of success. Secondary aims included comparing the cytological diagnosis with histopathology, evaluating the utility of concurrent locoregional lymph node cytology and assessing the procedure's complication rate. Gastrointestinal wall cytology from 75 dogs and 70 cats obtained between 2018 and 2023 were reviewed and categorised as successful (resulting in a diagnostic cytology report) and accurate (resulting in the correct diagnosis when compared to histopathology). Unsuccessful fine needle aspirates, not submitted for cytology, were not recorded. Variables recorded included animal signalment, lesion and lymph node's appearance on ultrasound, size, location, number of smears submitted and experience of the ultrasonographer. One hundred and fifty-two reports were analysed. Eighty-eight (58%) were successful: three normal epithelium, 21 inflammatory processes and 64 neoplasms. Variables associated with increased technical success included description of a mass, higher number of slides submitted and thickness of gastrointestinal lesion on ultrasound. Comparison with histopathology, performed for 17 lesions, showed discrepancies in eight, complete agreement in seven and partial in two. Eighty-four loco-regional lymph nodes were sampled, of which, 67 were successful (80%) and 52 brought additional clinical information (supporting GI wall cytology or diagnosing neoplasia not identified on GI wall cytology). No complication strictly attributable to gastrointestinal wall sampling was reported but when possibly related, death of the patient occurred in 2.5% of cases. Ultrasound-guided fine needle aspirate of gastrointestinal wall had moderate accuracy and was unsuccessful in 42% of cases, but technical success increased when sampling mass lesions, thicker intestinal layers and submitting more slides.

The EPICOVID19-BS study: a web-based epidemiological survey in bariatric patients

Abstract Purpose To assess the occurrence and severity of SARS-CoV-2 infection/COVID-19, frequency of symptoms, clinical manifestations and behaviours in a sample of patients undergoing bariatric surgery (BS). Methods The EPICOVID19-BS is an observational cross-sectional study conducted in Italy during the second wave of the COVID-19 pandemic (September 2021-February 2022). Patients with severe/extreme obesity undergoing BS were asked to complete an online multiple-choice questionnaire and to provide additional clinical information and blood biochemistry. Positive COVID-19 cases were defined by the combination of positive nasopharyngeal swab test results and/or positive serological test results. Sociodemographic, clinical and behavioural characteristics were compared between positive and negative COVID-19 cases. Results A total of 745 participants were enrolled (mean age 44.5 ± 10.5 years SD, 78% female). The proportion of positive COVID-19 cases was 20.4%. They were more likely to be health care workers, to have close contacts with confirmed cases, to use anti-inflammatory drugs, to have immune system disorders, to have previous CMV infection, to have lower cholesterol levels and to have less metabolic syndrome than negative cases. Infected participants significantly increased their use of national health resources for minor health problems. The majority of participants experienced flu-like symptoms and taste and smell disturbances. Only 9.6% were hospitalised and none required intubation. Conclusions Our results seem to support the evidence that patients undergoing BS have a low rate of severe SARS-CoV2. Further longitudinal studies in multiple obesity treatment centres are needed to more effectively monitor and control obesity in this specific population. Graphical Abstract

Evaluating Sleep Challenges in Hospitalized Youth.

To characterize sleep quality and sleep disruptions among youth hospitalized outside of the intensive care unit (ICU). Participants were eligible for the survey-based study if they were 8-17 years old, English-speaking, hospitalized for ≥3 days outside of the ICU, and developmentally able to understand surveys. Survey administration included a sleep diary, the Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), and a study-specific Inpatient Sleep Disruptors Questionnaire. The chart review provided additional clinical information. Descriptive and comparative statistics were performed to assess the association between overnight clinical monitoring and daytime sleepiness. Forty-five participants (mean age 13.4 years, 60% female), recruited between May and December 2022, were included in the study. Mean total sleep time (8.2 ± 1.7 hours) and ESS-CHAD score (8.6 ± 4.3) were normal with 79% reporting fair to good sleep the previous night.Participants rated alarms on equipment, vital signs, and noise as most disruptive to sleep. Participants with vital signs every four hours showed higher levels of daytime sleepiness compared with participants with vitals measured every shift (9.3 vs. 6.3; p=0.04). Most participants reported normal sleep, although there was wide variability with a portion with impaired sleep quality and elevated daytime sleepiness. Alarms on equipment, vital signs, and noise were most disruptive, and increased vital sign frequency was also associated with increased daytime sleepiness. In clinically stable pediatric patients, a reduction in vital sign monitoring overnight may be an important change to improve patient sleep.

An artificial intelligence-assisted clinical framework to facilitate diagnostics and translational discovery in hematologic neoplasia

The increasing volume and intricacy of sequencing data, along with other clinical and diagnostic data, like drug responses and measurable residual disease, creates challenges for efficient clinical comprehension and interpretation. Using paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) as a use case, we present an artificial intelligence (AI)-assisted clinical framework clinALL that integrates genomic and clinical data into a user-friendly interface to support routine diagnostics and reveal translational insights for hematologic neoplasia. We performed targeted RNA sequencing in 1365 cases with haematological neoplasms, primarily paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) from the AIEOP-BFM ALL study. We carried out fluorescence in situ hybridization (FISH), karyotyping and arrayCGH as part of the routine diagnostics. The analysis results of these assays as well as additional clinical information were integrated into an interactive web interface using Bokeh, where the main graph is based on Uniform Manifold Approximation and Projection (UMAP) analysis of the gene expression data. At the backend of the clinALL, we built both shallow machine learning models and a deep neural network using Scikit-learn and PyTorch respectively. By applying clinALL, 78% of undetermined patients under the current diagnostic protocol were stratified, and ambiguous cases were investigated. Translational insights were discovered, including IKZF1plus status dependent subpopulations of BCR::ABL1 positive patients, and a subpopulation within ETV6::RUNX1 positive patients that has a high relapse frequency. Our best machine learning models, LDA and PASNET-like neural network models, achieve F1 scores above 97% in predicting patients' subgroups. An AI-assisted clinical framework that integrates both genomic and clinical data can take full advantage of the available data, improve point-of-care decision-making and reveal clinically relevant insights promptly. Such a lightweight and easily transferable framework works for both whole transcriptome data as well as the cost-effective targeted RNA-seq, enabling efficient and equitable delivery of personalized medicine in small clinics in developing countries. German Ministry of Education and Research (BMBF), German Research Foundation (DFG) and Foundation for Polish Science.

Novel Tools for Single Comparative and Unified Evaluation of Qualitative and Quantitative Bioassays: SS/PV-ROC and SS-J/PV-PSI Index-ROC Curves with Integrated Concentration Distributions, and SS-J/PV-PSI Index Cut-Off Diagrams.

Background: This investigation is both a study of potential non-invasive diagnostic approaches for the bladder cancer biomarker UBC® Rapid test and a study including novel comparative methods for bioassay evaluation and comparison that uses bladder cancer as a useful example. The objective of the paper is not to investigate specific data. It is used only for demonstration, partially to compare ROC methodologies and also to show how both sensitivity/specificity and predictive values can be used in clinical diagnostics and decision making. This study includes ROC curves with integrated cut-off distribution curves for a comparison of sensitivity/specificity (SS) and positive/negative predictive values (PPV/NPV or PV), as well as SS-J index/PV-PSI index-ROC curves and SS-J/PV-PSI index cut-off diagrams (J = Youden, PSI = Predictive Summary Index) for the unified direct comparison of SS-J/PV results achieved via quantitative and/or qualitative bioassays and an identification of optimal separate or unified index cut-off points. Patients and Methods: According to the routine diagnostics, there were 91 patients with confirmed bladder cancer and 1152 patients with no evidence of bladder cancer, leading to a prevalence value of 0.073. This study performed a quantitative investigation of used-up test cassettes from the visual UBC® Rapid qualitative point-of-care assay, which had already been applied in routine diagnostics. Using a photometric reader, quantitative data could also be obtained from the test line of the used cassettes. Interrelations between SS and PV values were evaluated using cumulative distribution analysis (CAD), SS/PV-ROC curves, SS-J/PV-PSI index-ROC curves, and the SS-J/PV-PSI index cut-off diagram. The maximum unified SS-J/PV-PSI index value and its corresponding cut-off value were determined and calculated with the SS-J/PV-PSI index cut-off diagram. Results: The use of SS/PV-ROC curves with integrated cut-off concentration distribution curves provides improved diagnostic information compared to "traditional" ROC curves. The threshold distributions integrated as curves into SS/PV-ROC curves and SS-J/PV-PSI index-ROC curves run in opposite directions. In contrast to the SS-ROC curves, the PV-ROC and the novel PV-PSI index-ROC curves had neither an area under the curve (AUC) nor a range from 0% to 100%. The cut-off level of the qualitative assay was 7.5 µg/L, with a sensitivity of 65.9% and a specificity of 63.3%, and the PPV was 12.4% and the NPV was 95.9%, at a threshold value of 12.5 µg/L. Based on these set concentrations, the reader-based evaluation revealed a graphically estimated 5% increase in sensitivity and a 13% increase in specificity, as compared to the visual qualitative POC test. In the case of predictive values, there was a gain of 8% for PPV and 10% for NPV. The index values and cut-offs were as follows: visual SS-J index, 0.328 and 35 µg/L; visual PV-PSI index, 0.083 and 5.4 µg/L; maximal reader Youden index, 0.0558 and 250 µg/L; and maximal PV-PSI index, 0.459 and 250 µg/L, respectively. The maximum unified SS-J/PV-PSI index value was 0.32, and the cut-off was 43 µg/L. The reciprocal SS-J index correctly detected one out of three patients, while the reciprocal PV-PSI index gave one out of twelve patients a correct diagnosis. Conclusions: ROC curves including cut-off distribution curves supplement the information lost in "traditionally plotted" ROC curves. The novel sets of ROC and index-ROC curves and the new SS/PV index cut-off diagrams enable the simultaneous comparison of sensitivity/specificity and predictive value profiles of diagnostic tools and the identification of optimal cut-off values at maximal index values, even in a unifying SS/PV approach. Because the curves within an SS-J/PV-PSI index cut-off diagram are distributed over the complete cut-off range of a quantitative assay, this field is open for special clinical considerations, with the need to vary the mentioned clinical diagnostic parameters. Complete or partial areas over the x-axis (AOX) can be calculated for summarized quantitative or qualitative effectivity evaluations with respect to single and/or unified SS-J and PV-PSI indices and with respect to single, several, or several unified assays. The SS-J/PV-PSI index-AOX approach is a new tool providing additional joint clinical information, and the reciprocal SS-J indices can predict the number of patients with a correct diagnosis and the number of persons who need to be examined in order to correctly predict a diagnosis of the disease. These methods could be used in applications like medical or plant epidemiology, machine learning algorithms, and neural networks.

GNB1 and obesity: Evidence for a correlation between haploinsufficiency and syndromic obesity.

Most patients with GNB1 encephalopathy have developmental delay and/or intellectual disability, brain anomalies and seizures. Recently, two cases with GNB1 encephalopathy caused by haploinsufficiency have been reported that also show a Prader-Willi-like phenotype of childhood hypotonia and severe obesity. Here we present three new cases from our expert centre for genetic obesity in which GNB1 truncating and splice variants, probably leading to haploinsufficiency, were identified. They all have obesity, hyperphagia and intellectual deficit. The clinical cases and their weight courses are presented, together with a review of all 68 published cases with GNB1 encephalopathy. Information on weight was not mentioned in most of these articles, so we contacted authors for additional clinical information on weight status and hyperphagia. Of the 42 patients whose weight status we could determine, obesity was present in 8 patients (19%). Obesity is significantly over-represented in the group with truncating and splicing variants. In this group, we see an obesity prevalence of 75%. Since GNB1 has been linked to several key genes in the hypothalamic leptin-melanocortin pathway, which regulates satiety and energy expenditure, our data support the potential association between GNB1 haploinsufficiency and genetic obesity. We also suggest GNB1 is a candidate gene for the known obesity phenotype of the 1p36 microdeletion syndrome given this chromosomal region includes the GNB1 gene. Knowledge of an additional obesity phenotype is important for prognosis, early interventions against obesity and awareness when prescribing weight-inducing medication.

The PRECISE-DYAD protocol: linking maternal and infant health trajectories in sub-Saharan Africa.

PRECISE-DYAD is an observational cohort study of mother-child dyads running in urban and rural communities in The Gambia and Kenya. The cohort is being followed for two years and includes uncomplicated pregnancies and those that suffered pregnancy hypertension, fetal growth restriction, preterm birth, and/or stillbirth. The PRECISE-DYAD study will follow up ~4200 women and their children recruited into the original PRECISE study. The study will add to the detailed pregnancy information and samples in PRECISE, collecting additional biological samples and clinical information on both the maternal and child health.Women will be asked about both their and their child's health, their diets as well as undertaking a basic cardiology assessment. Using a case-control approach, some mothers will be asked about their mental health, their experiences of care during labour in the healthcare facility. In a sub-group, data on financial expenditure during antenatal, intrapartum, and postnatal periods will also be collected. Child development will be assessed using a range of tools, including neurodevelopment assessments, and evaluating their home environment and quality of life. In the event developmental milestones are not met, additional assessments to assess vision and their risk of autism spectrum disorders will be conducted. Finally, a personal environmental exposure model for the full cohort will be created based on air and water quality data, combined with geographical, demographic, and behavioural variables. The PRECISE-DYAD study will provide a greater epidemiological and mechanistic understanding of health and disease pathways in two sub-Saharan African countries, following healthy and complicated pregnancies. We are seeking additional funding to maintain this cohort and to gain an understanding of the effects of pregnancies outcome on longer-term health trajectories in mothers and their children.

SARS-CoV-2 PCR cycle threshold value at admission might not be a good predictor of in-hospital COVID-19-associated AKI.

Acute kidney injury (AKI) is a prevalent complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and a predictor of disease severity and mortality; furthermore, a prompt diagnosis and treatment of this complication may enhance COVID-19 prognosis. Therefore, we aim to investigate potential risk factors for SARS-CoV-2-associated AKI, including SARS-CoV-2 PCR cycle threshold value (CT value), which correlation with AKI is conflicting. This case-control study included 110 hospitalized patients with SARS-CoV-2-associated AKI as cases and 110 random SARS-CoV-2 hospitalized patients as controls. Reverse transcription real-time PCR of admission nasopharyngeal swabs evaluated E gene cycle thresholds. Additional clinical and paraclinical information extracted from medical records. The patient's status at discharge, and 14 and 30 days after discharge. Therefore, after adjusting for age and gender, the correlation between variables was assessed. SARS-CoV-2 AKI is significantly associated with age above 60, hypertension, diabetes mellitus, ischemic heart disease, and underlying kidney diseases. Abnormal admission hemoglobin or alkaline phosphatase, proteinuria or hematuria in urine sediment, and abnormal creatinine during hospitalization were the paraclinical features correlated to SARS-CoV-2 AKI. AKI group demonstrated greater in-hospital, 14- and 30-day mortality. Nevertheless, this study did not evidence a correlation between the admission CT value and mortality or AKI. Admission CT values provide limited information regarding the dynamic viral load and varying hospitalization time points; thus, they may not be reliable for predicting the prognosis and complications of COVID-19 in all populations. Further studies with serial CT measurements or symptom onset time adjustment are recommended.

Multi-segment foot kinematics during gait in children with spastic cerebral palsy

BackgroundFoot deformities (e.g. planovalgus and cavovarus) are very common in children with spastic cerebral palsy (CP), with the midfoot often being involved. Dynamic foot function can be assessed with 3D gait analysis including a multi-segment foot model. Incorporating a midfoot segment in such a model, allows quantification of separate Chopart and Lisfranc joint kinematics. Yet, midfoot kinematics have not previously been reported in CP. Research questionsWhat is the difference in multi-segment kinematics including midfoot joints between common foot deformities in CP and typically-developing feet? Methods103 feet of 57 children with spastic CP and related conditions were retrospectively included and compared with 15 typically-developing children. All children underwent clinical gait analysis with the Amsterdam Foot Model marker set. Multi-segment foot kinematics were calculated for three strides per foot and averaged. A k-means cluster analysis was performed to identify foot deformity groups that were present within CP data. The deformity type represented by each cluster was based on the foot posture index. Kinematic output of the clusters was compared to typically-developing data for a static standing trial and for the range of motion and kinematic waveforms during walking, using regular and SPM independent t-tests respectively. ResultsA neutral, planovalgus and varus cluster were identified. Neutral feet showed mostly similar kinematics as typically-developing data. Planovalgus feet showed increased ankle valgus and Chopart dorsiflexion, eversion and abduction. Varus feet showed increased ankle varus and Chopart inversion and adduction. SignificanceThis study is the first to describe Chopart and Lisfranc joint kinematics in different foot deformities of children with CP. It shows that adding a midfoot segment can provide additional clinical and kinematic information. It highlights joint angles that are more distinctive between deformities, which could be helpful to optimize the use of multi-segment foot kinematics in the clinical decision making process.

Abstract 2933: Use of artificial intelligence to facilitate reporting of comprehensive genomic profiling tests

Abstract Background: Comprehensive genomic profiling (CGP) tests have been nationally reimbursed in Japan since 2019, and all test results must be discussed by molecular tumor boards (MTBs). More than 60,000 patients have taken the CGP tests at over 200 government-designated hospitals by November 2023. Streamlining decision-making by MTBs and standardizing interpretation of test results is important. We evaluated the performance of Chrovis, an annotation algorithm for reporting CGP tests. Methods: We retrospectively reviewed the reporting process of all approved CGP tests done at The University of Tokyo Hospital and its 12 affiliated hospitals between December 2019 and November 2023. Chrovis referenced several public knowledge databases and used natural language processing to annotate each genetic variant and generated reports using the automated program. The MTB reviewed all reports with the addition of clinical information and made any necessary changes Recommendations on disclosure of germline findings were made in accordance with the national guideline. Results: Among the 2,819 Chrovis reports created, 1,927 were tumor-only FoundationOne CDx (F1CDx), 483 were tumor/normal paired NCC Oncopanel (NOP), and 409 were FoundationOne Liquid CDx (F1Liquid) panels. Among them, 603 changes in 496 reports (17.6% of all reports) were made by the MTB. The most common type of change was germline disclosure with 208 changes (7.4%), followed by clinical trial information (196 changes, 7.0%) and pathogenicity (107 changes, 3.8%). Gene alterations that led to most changes in germline disclosure were TP53, SMAD4, CDKN2A, TERT, and NF2 (42, 22, 16, 13, and 13 changes, respectively). Changes in clinical trial information were frequently observed in TP53, NF1, BRAF, ERBB2, and KRAS (25, 20, 19, 16, and 16 changes, respectively). F1CDx required the greatest number of changes (404/1927, 21.0%) followed by F1Liquid (53/409, 13.0%) and NOP (39/483, 8.1%) (p &amp;lt; 0.001). Changes to germline disclosure were made in 9.1% of F1CDx reports, 5.4% of F1Liquid reports, and 2.1% of NOP reports (p &amp;lt; 0.001). Changes to clinical trial information were made in 8.3%, 4.4%, and 3.9%, respectively (p &amp;lt; 0.001). Conclusions: Chrovis-generated CGP reports did not require any changes in 82%s, suggesting that artificial intelligence reporting may lessen the burden of MTBs while contributing to its standardization. Recommendation for germline disclosure requires manual supervision, and improvements in clinical trial databases are required to correctly recommend genomically matched trials to patients. Citation Format: Hidenori Kage, Takashi Aoki, Aya Shinozaki-Ushiku, Kousuke Watanabe, Nana Akiyama, Hideaki Isago, Miho Ogawa, Kazunaga Ishigaki, Hiroshi Kobayashi, Takuya Miyagawa, Jun Omatsu, Yuki Saito, Kazuhito Sasaki, Yasuyoshi Sato, Yusuke Sato, Nobumi Suzuki, Shota Tanaka, Motohiro Kato, Masahiko Tanabe, Kenji Tatsuno, Tetsuo Ushiku, Kunihiro Nishimura, Hiroyuki Aburatani, Katsutoshi Oda. Use of artificial intelligence to facilitate reporting of comprehensive genomic profiling tests [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2933.

Serum tumor markers for response prediction and monitoring of advanced lung cancer: A review focusing on immunotherapy and targeted therapies.

The value of serum tumor markers (STMs) in the current therapeutic landscape of lung cancer is unclear. This scoping review gathered evidence of the predictive, prognostic, and monitoring value of STMs for patients with advanced lung cancer receiving immunotherapy (IT) or targeted therapy (TT). Literature searches were conducted (cut-off: May 2022) using PubMed and Cochrane CENTRAL databases. Medical professionals advised on the search strategies. Study heterogeneity limited the evidence and inferences from the 36 publications reviewed. While increased baseline levels of serum cytokeratin 19 fragment antigen (CYFRA21-1) and carcinoembryonic antigen (CEA) may predict IT response, results for TT were less clear. For monitoring IT-treated patients, STM panels (including CYFRA21-1, CEA, and neuron-specific enolase) may surpass the power of single analyses to predict non-response. CYFRA21-1 measurement could aid in monitoring TT-treated patients, but the value of CEA in this context requires further investigation. Overall, baseline and dynamic changes in individual or combined STM levels have potential utility to predict treatment outcome and for monitoring of patients with advanced lung cancer. In advanced lung cancer, STMs provide additional relevant clinical information by predicting treatment outcome, but further standardization and validation is warranted.

Surveillance for Lyme Disease After Implementation of a Revised Case Definition - United States, 2022.

Lyme disease, a tickborne zoonosis caused by certain species of Borrelia spirochetes, is the most common vectorborne disease in the United States. Approximately 90% of all cases are reported from 15 high-incidence jurisdictions in the Northeast, mid-Atlantic, and upper-Midwest regions. After the implementation of a revised surveillance case definition in 2022, high-incidence jurisdictions report cases based on laboratory evidence alone, without need for additional clinical information. In 2022, 62,551 Lyme disease cases were reported to CDC, 1.7 times the annual average of 37,118 cases reported during 2017-2019. Annual incidence increased most in older age groups, with incidence among adults aged ≥65 years approximately double that during 2017-2019. The sharp increase in reported Lyme disease cases in 2022 likely reflects changes in surveillance methods rather than change in disease risk. Although these changes improve standardization of surveillance across jurisdictions, they preclude detailed comparison with historical data.