Explore the vast range of titles available.

Abstract Context The 2019 American Association of Clinical Endocrinologists guidelines suggested peak GH-cutoffs to glucagon test (GST) of ≤3 and ≤1 µg/L in the diagnosis of permanent GH deficiency (GHD) during the transition phase. Objective The aim of the study was to evaluate the accuracy of GST compared to insulin tolerance test (ITT) in the definition of GHD at adult height achievement. Patients and methods Ninety-seven subjects with childhood-onset GHD (median age, 17.39 years) underwent ITT, GST, and IGF-1 testing; 44 subjects were idiopathic (isolated GHD), 35 moderate organic GHD (0-2 hormone deficiencies) and 18 severe organic GHD (≥3 hormone deficiencies). Results Bland and Altman analysis showed a high consistency of GH peak measures after ITT and GST. Receiver operating characteristic analysis identified 7.3 μg/L as the optimal GH peak cutoff to GST [95% confidence interval (CI) 4.15-8.91; sensitivity 95.7%, specificity 88.2%, positive predictive value (PPV) 88.0%, negative predictive value (NPV) 95.7%] able to correctly classify 91.8% of the entire cohort while 5.8 μg/L was the best GH peak cutoff able to correctly classify 91.4% of moderate organic GHD patients (95% CI 3.16-7.39; sensitivity 96.0%, specificity 80.0%, PPV 92.3%, NPV 88.9%). Patients with ≥3 hormone deficiencies showed a GH peak <5 μg/L at ITT and <5.8 μg/L at GST but 1. The optimal cutoff for IGF-1 was −1.4 SD score (95% CI −1.94 to 0.77; sensitivity 75%, specificity 94%, PPV 91.7%, NPV 81.0%) that correctly classified 85.1% of the study population. Conclusion A GH peak to GST <5.8 μg/L represents an accurate diagnostic cutoff for young adults with childhood-onset GHD and high pretest probability of permanent GHD.

Disclosure: N. Di Iorgi: None. D. Guglielmi: None. N. Flavia: None. A. Allegri: None. D. Fava: None. E. Casalini: None. G. Patti: None. M. Maghnie: None. Objectives: To evaluate the accuracy of the Glucagon test (GST) compared with the Insulin Tolerance test (ITT) as the gold standard in the diagnosis of Growth Hormone deficiency (GHD) in young adults with childhood-onset GHD (COGHD). Methods: Eighty-six subjects with COGHD (33F, 55M) were evaluated by ITT and GST stimulation tests and IGF-1 SDS at adult height achievement (median age of 17.5; IQR 13.9-18.4 years). Subjects were recruited from a single Center and based on the AACE 2019 Guidelines [1] classified as 1. idiopathic isolated GHD (I-GHD n=40 with normal brain MRI); 2. organic moderate GHD (omGHD with less than 3 pituitary deficiencies-PD and IGF-1<0 SDS, total n=40; n=12 midline defects, n=2 ALL, n=26 CNS tumors); 3. congenital/genetic defects/organic severe GHD (osGHD ≥3 PD and IGF-1 <-2 SDS, total n=6; n=1 midline defect, n=5 CNS tumors). ROC analyses were performed in order to analyze the Sensitivity (Se) and Specificity (Sp) of the GH peak after GST and of IGF-1 SDS compared to ITT. A peak GH value <6μg/L after ITT was suggestive of permanent GHD [2]. Results: Median GH peak to ITT (0.2; IQR 0.01-0.7 μg/L) and GST (0.1; IQR 0.01-1.4μg/L) were lower in osGHD compared to I-GHD subjects (15.0; IQR 8.6-21.9 to ITT and 12.6; IQR 10.5-18.8 μg/L to GST, P’s <0.0001); similarly, GH peak to ITT (2.1; IQR 1.1-6.8 μg/L) and GL (2.7; IQR 1.2-5.8) were lower in omGHD compared to I-GHD subjects (P’s <0.0001). Mean IGF-1 were also lower in osGHD (-3.2 SDS; IQR -7.4- -2.9, P<0.0001) and in omGHD (-2.0 SDS; IQR -2.8 - -0.7; P<0.0001) compared to I-GHD subjects (0,1; IQR -0.6-1.1SDS). A GH peak value to GST of 7.59 mcg/L (Se 92.3%, Sp of 87.2%; AUC=0.94; 95% CI, 0.89-0.99) correctly classified 89.5% of the entire cohort while an IGF-1 cut-off of -1.45 SDS (Se 73%; Sp 93.5%; AUC=0.84; 95% CI, 0.75 - 0.94) correctly classified 83,1%. A GH peak value to GST of 5.81 mcg/L (Se 96.6%, Sp of 81.8%; AUC=0.95; 95% CI, 0.88-1.02) correctly classified 92.5% of omGHD patients while an IGF-1 cut-off of -1.64 SDS (Se 72.3%, Sp of 90.9%; AUC=0.94; 95% CI, 0.89-0.99) correctly classified 77.5% omGHD patients. Median BMI SDS was higher in patients with osGHD (1.8; IQR 1,6- 2.2, P<0.001) and omGHD (0.6; IQR 0.1- 1.8, P<0.001) compared to I-GHD (0.2; IQR -0.7- 1.1). GH peak to GST correlated with BMI SDS only in the total cohort (r -0.313, P=0.0031). Conclusions: Our results suggest that a peak value <6 μg/L after GST is accurate in detecting permanent GHD during transition in a cohort of patients with organic GHD with less than 3 pituitary defects and IGF-1 values <0 SDS; the GH response to GST could be affected by BMI SDS, but further studies are needed. [1] Yuen KCJ et al. Endocr Pract 2019; 25 (11):1191-1232. [2] Maghnie M et al, EJE 2005; 152:589-596. Presentation: Thursday, June 15, 2023

Background/Objectives: Intramural pregnancy (IMP) is a rare type of ectopic pregnancy where the embryo implants within the uterine myometrium. This condition carries a high risk of massive hemorrhage, uterine rupture, and potentially life-threatening complications. Methods: We present a case of a 35-year-old patient who underwent in vitro fertilization (IVF) and was diagnosed with an IMP located in the back-isthmian portion of the uterus by ultrasound scan. Results: We performed a conservative treatment approach based on the gestational sac location and the patient’s stable clinical condition and desire for future fertility. We first administered mifepristone 600 mg, followed by intracavitary methotrexate under ultrasound guidance. Although originally planned, a uterine artery embolization was not performed due to the evidence of bilateral anastomoses between the uterine and ovarian arteries. Progressive reabsorption of pregnancy was observed over the course of 8 months. Conclusions: Non-surgical management can be considered for IMP, thus allowing fertility preservation.

Intratumour heterogeneity and phenotypic plasticity drive tumour progression and therapy resistance 1 , 2 . Oncogene dosage variation contributes to cell-state transitions and phenotypic heterogeneity 3 , thereby providing a substrate for somatic evolution. Nonetheless, the genetic mechanisms underlying phenotypic heterogeneity are still poorly understood. Here we show that extrachromosomal DNA (ecDNA) is a major source of high-level focal amplification in key oncogenes and a major contributor of MYC heterogeneity in pancreatic ductal adenocarcinoma (PDAC). We demonstrate that ecDNAs drive varying levels of MYC dosage, depending on their regulatory landscape, enabling cancer cells to rapidly and reversibly adapt to microenvironmental changes. In the absence of selective pressure, a high ecDNA copy number imposes a substantial fitness cost on PDAC cells. We also show that MYC dosage affects cell morphology and dependence of cancer cells on stromal niche factors. Our work provides a detailed analysis of ecDNAs in PDAC and describes a new genetic mechanism driving MYC heterogeneity in PDAC. In a model of pancreatic ductal adenocarcinoma, extrachromosomal DNAs are shown to be a source of high-level focal amplification driving MYC heterogeneity and phenotypic adaptation.

Background Accurate estimation of the imminent fragility fracture risk currently represents a challenging task. The novel Fragility Score (FS) parameter, obtained during a Radiofrequency Echographic Multi Spectrometry (REMS) scan of lumbar or femoral regions, has been developed for the non-ionizing estimation of skeletal fragility. Aims The aim of this study was to assess the performance of FS in the early identification of patients at risk for incident fragility fractures with respect to bone mineral density (BMD) measurements. Methods Data from 1989 Caucasians of both genders were analysed and the incidence of fractures was assessed during a follow-up period up to 5 years. The diagnostic performance of FS to discriminate between patients with and without incident fragility fracture in comparison to that of the BMD T-scores measured by both Dual X-ray Absorptiometry (DXA) and REMS was assessed through ROC analysis. Results Concerning the prediction of generic osteoporotic fractures, FS provided AUC = 0.811 for women and AUC = 0.780 for men, which resulted in AUC = 0.715 and AUC = 0.758, respectively, when adjusted for age and body mass index (BMI). For the prediction of hip fractures, the corresponding values were AUC = 0.780 for women and AUC = 0.809 for men, which became AUC = 0.735 and AUC = 0.758, respectively, after age- and BMI-adjustment. Overall, FS showed the highest prediction ability for any considered fracture type in both genders, resulting always being significantly higher than either T-scores, whose AUC values were in the range 0.472–0.709. Conclusion FS displayed a superior performance in fracture prediction, representing a valuable diagnostic tool to accurately detect a short-term fracture risk.

Impairment of episodic memory is largely considered the main cognitive marker of prodromic Alzheimer's disease (AD). Nevertheless, the neuropathological process in AD starts several years before and, apart from biomarkers well defined in the Amyloid (A), Tauopathy (T), Neurodegeneration (N) framework, early clinical and neuropsychological markers able to detect mild cognitive impairment (MCI) due to AD before the appearance of memory disorders are lacking in clinical practice. Investigations on semantic memory have shown promising results in providing an earlier marker of dementia in MCI patients. A total of 253 MCI subjects were followed up every 6 months for 6 years-186 converted to dementia and 67 remained stable at the sixth year of follow-up. Twenty-seven patients progressed in the first 2 years (fast converters), 107 in the third to fourth year (intermediate converters), and 51 after the fourth year of follow-up (slow converters). Stable MCI subjects performed better than fast decliners in Mini-Mental State Examination (MMSE), several long-term memory scores, and category verbal fluency test (CFT); stable and intermediate converters differ only in MMSE and CFT tests; and stable and slow converters differ only in MMSE and phonological/semantic discrepancy score. Early impairment of semantic memory could predict the evolution to AD before the onset of episodic memory disorders, and the discrepancy between phonological and semantic verbal fluency could be able to detect this impairment in advance in respect of simple CFT tests. The assessment of different aspects of semantic memory and its degradation could represent an early cognitive marker to intercept MCI due to AD in clinical practice.

Background Digital interventions (DIs) have emerged as promising tools for promoting mental health in the workplace. However, evidence on if, how, and under what circumstances they affect positive outcomes requires elucidation. This systematic realist review aimed to synthesize current knowledge on contexts, mechanisms, and outcomes of workplace DIs to enhance mental health at work. Methods The review integrates elements of both systematic and realist review methodologies. Forty-four workplace mental health DIs studies were gathered through a systematic electronic search using PsycNet, Scopus, Web of Science, and PubPsych. Results Results showed that demographics, previous mental health, and personal skills were the main individual context factors influencing the success of DIs. Key mechanisms were DIs usage, frequency, adherence, and relevance of content triggering positive perceptual shifts. Results showed improvements in psychological resources, wellbeing, and affect. Reduced ill-health symptoms were also evidenced. Five propositions were developed on the contexts and mechanisms under which digital interventions yield positive outcomes for mental health at work. Conclusions This study highlights several areas where future research can expand our understanding of DIs in the workplace by examining interactions between mechanisms and cultural aspects influencing implementation.

Purpose of Review This narrative review article aims to show the actual role of imaging, in particular MRI, and the role of VI-RADS Score, in recognition and follow-up of the tumor. Recent Findings A team of professionals created VI-RADS with the goal of standardizing the acquisition and interpretation of multiparametric-MRI in bladder cancer. Summary Bladder cancer is the most common cancer involving the urinary system. It is the fourth most common urological cancer in men and the second most frequent cancer affecting the urinary tract. Main risks factors are advanced age, male sex, and cigarette smoking. Bladder cancer ranges from unaggressive and usually non-invasive tumors that recur and commit patients to long-term invasive surveillance, to aggressive and invasive tumors with high disease-specific mortality. At the time of diagnosis, 70% of patients are experiencing non-muscle-invasive bladder cancer. Vesical imaging-reporting and data system score (VI-RADS) is a scoring system useful to standardize the approach to multiparametric-MRI interpretation, and reporting for bladder cancer.

Background: Family caregivers of patients with dementia are at high risk of stress and burden, and quarantine due to the coronavirus disease 2019 (COVID-19) pandemic may have increased the risk of psychological disturbances in this population. The current study was carried out during the national lockdown declared in March 2020 by the Italian government as a containment measure of the first wave of the coronavirus pandemic and is the first nationwide survey on the impact of COVID-19 lockdown on the mental health of dementia informal caregivers. Methods: Eighty-seven dementia centers evenly distributed on the Italian territory enrolled 4,710 caregiver–patient pairs. Caregivers underwent a telephone interview assessing classical symptoms of caregiver stress and concern for the consequences of COVID-19 infection on patient’s health. We calculated prevalence of symptoms and regressed them on various potential stress risk factors: caregivers’ sociodemographic characteristics and lifestyle, patients’ clinical features, and lockdown-related elements, like discontinuity in medical care. Results: Approximately 90% of caregivers reported at least one symptom of stress, and nearly 30% reported four or more symptoms. The most prevalent symptoms were concern for consequences of COVID-19 on patient’s health (75%) and anxiety (46%). The main risk factors for stress were identified as a conflicting relationship with the patient and discontinuity in assistance, but caregiver’s female sex, younger age, lower education, and cohabitation with the patient also had an impact. Availability of help from institutions or private individuals showed a protective effect against sense of abandonment but a detrimental effect on concern about the risk for the patient to contract COVID-19. The only protective factor was mild dementia severity, which was associated with a lower risk of feeling isolated and abandoned; type of dementia, on the other hand, did not affect stress risk. Conclusion: Our results demonstrate the large prevalence of stress in family caregivers of patients with dementia during the COVID-19 pandemic and have identified both caregivers and situations at a higher risk of stress, which should be taken into account in the planning of interventions in support of quarantined families and patients.

An unprecedented wave of patients with acute respiratory failure due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) hit emergency departments (EDs) in Lombardy, starting in the second half of February 2020. This study describes the direct and indirect impacts of the SARS-CoV-2 outbreak on an urban major-hospital ED. Data regarding all patients diagnosed with COVID-19 presenting from February 1 to March 31, 2020, were prospectively collected, while data regarding non-COVID patients presenting within the same period in 2019 were retrospectively retrieved. ED attendance dropped by 37% in 2020. Two-thirds of this reduction occurred early after the identification of the first autochthonous COVID-19 case in Lombardy, before lockdown measures were enforced. Hospital admissions of non-COVID patients fell by 26%. During the peak of COVID-19 attendance, the ED faced an extraordinary increase in: patients needing oxygen (+239%) or noninvasive ventilation (+725%), transfers to the intensive care unit (+57%), and in-hospital mortality (+309%), compared with the same period in 2019. The COVID-19 outbreak determined an unprecedented upsurge in respiratory failure cases and mortality. Fear of contagion triggered a spontaneous, marked reduction of ED attendance, and, presumably, some as yet unknown quantity of missed or delayed diagnoses for conditions other than COVID-19.