Prospective Multicenter Study Research Articles

Outcomes of Patients With Early and Locally Advanced Lung Cancer: Protocol for the Italian Lung Cancer Observational Study (LUCENT).

Lung cancer, predominantly non-small cell lung cancer (NSCLC), remains a formidable challenge, necessitating an in-depth understanding of evolving treatment paradigms. The Italian Lung Cancer Observational Study (LUCENT) addresses this need by investigating the outcomes of patients with early and locally advanced lung cancer in Italy. With a focus on real-world data and patient registries, this study aims to provide comprehensive insights into clinical, psychosocial, and economic impacts, contributing to informed decision-making in health care. LUCENT is a prospective observational multicenter cohort study enrolling patients eligible for minimally invasive manual, robot-assisted, or traditional open surgery. The study will develop a web-based registry to collect longitudinal surgical, oncological, and socioeconomic outcome data. The primary objectives include performance assessment through the establishment of national benchmarks based on risk-adjusted outcomes and processes of care indicators. The secondary objectives encompass economic and psychosocial impact assessments of innovative technologies and treatment pathways. The multicenter design ensures a diverse and representative study population. The evolving landscape of NSCLC treatment necessitates a nuanced approach with consideration of the dynamic shifts in therapeutic strategies. LUCENT strives to fill existing knowledge gaps by providing a platform for collecting and analyzing real-world data, emphasizing the importance of patient-reported outcomes in enhancing the understanding of the disease. By developing a web-based registry, the study not only facilitates efficient data collection but also addresses the limitations of traditional methods, such as suboptimal response rates and costs associated with paper-and-pencil questionnaires. Recruitment will be conducted from January 01, 2024, to December 31, 2026. Follow-up will be performed for a minimum of 2 years. The study will be completed in the year 2028. LUCENT's potential implications are substantial. Establishing national benchmarks will enable a thorough evaluation of outcomes and care processes, guiding clinicians and policymakers in optimizing patient management. Furthermore, the study's secondary objectives, focusing on economic and psychosocial impacts, align with the contemporary emphasis on holistic cancer care. Insights gained from this study may influence treatment strategies, resource utilization, and patient well-being, thereby contributing to the ongoing refinement of lung cancer management. ClinicalTrials.gov NCT05851755; https://clinicaltrials.gov/study/NCT05851755. ISRCTN 67197140; https://www.isrctn.com/ISRCTN67197140. PRR1-10.2196/57183.

Physical activity levels are positively related to progression-free survival and reduced adverse events in advanced ER+ breast cancer.

Increased levels of physical activity are associated with a reduction of breast cancer mortality, especially in postmenopausal women with positive hormone receptor status. So far, previous observational case-control and cohort studies have focused on associations between overall leisure time physical activity and survival of women with breast cancer in general. In this multicenter prospective cohort study, conducted in Germany between 30th August 2012 to 29th December 2017, we investigated general physical activity in a homogenous sample of n = 1440 postmenopausal women with advanced (inoperable locally advanced or metastatic), hormone receptor-positive breast cancer receiving the same therapy (everolimus and exemestane). Self-reported physical activity was assessed using the Godin Leisure Time Exercise Questionnaire (GLTEQ) before and every 3months during treatment. Participants were then classified into "active" and "insufficiently active" to screen their activity behavior the week prior to medical treatment. In addition, changes in physical activity patterns were assessed. Adjusted Cox regression analyses were performed for the activity categories to determine hazard ratios (HR). Besides progression-free survival (PFS), adverse events (AEs), QoL, and fatigue were assessed every 3months until study termination. Compared to "insufficiently active" patients, "active" individuals indicated a significantly longer PFS (HR: 0.84 [0.74; 0.984], p = .0295). No significant differences were observed for changes of physical activity behavior. Patients who reported to be "active" at baseline revealed significantly fewer AEs compared to "insufficiently" active patients. In detail, both severe and non-severe AEs occurred less frequently in the "active" patients group. In line with that, QoL and fatigue were better in physical "active" patients compared to their insufficient active counterparts at the last post-baseline assessment. Participants who remained or become active indicated less AEs, a higher QoL, and reduced fatigue levels. Physical activity behavior prior to medical treatment might have prognostic value in patients with advanced breast cancer in terms of extending the PFS. Moreover, physical activity before and during treatment may reduce treatment-related side effects and improve patients' QoL and fatigue. EUPAS9462. Registered 30th October 2012 "retrospectively registered."

Comparison of Patient-Reported Outcomes Between Active Surveillance and Immediate Lobectomy in Patients with Low-Risk Papillary Thyroid Microcarcinoma: Initial Findings from the KoMPASS Cohort.

Background: Patients diagnosed with low-risk papillary thyroid microcarcinoma (PTMC) face the decision between thyroid lobectomy and active surveillance (AS). This study aimed to investigate the factors influencing treatment decisions in low-risk PTMC and to compare the quality of life (QoL) according to the treatment plan. Methods: The multicenter prospective cohort study comparing AS and thyroid lobectomy was conducted. Clinical characteristics were compared between the AS and Lobectomy groups. QoL questionnaires were administered every 6 months in the initial year and annually thereafter. Results: A total of 927 patients (453 in the AS group and 474 in the Lobectomy group) with low-risk PTMC were included in this study. The mean age was 47.4 ± 12.2 years, and 72.2% of the patients were women. Older age (odd ratio [OR] 1.04, confidence interval [CI] 1.02-1.05, p < 0.001), smaller tumor size (OR 0.78, CI 0.69-0.87, p < 0.001), family history of thyroid cancer (OR 1.48, CI 1.03-2.12, p = 0.035), prior awareness of AS (OR 1.53, CI 1.16-2.02, p = 0.003), and higher income (OR 1.79, CI 1.13-2.83, p = 0.013) were significantly associated with a higher likelihood of choosing AS. The median follow-up was 27.3 months (23.9-43.9) in the AS group and 28.7 months (20.4-44.5) in the Lobectomy group. During the follow-up period, the AS group showed significantly better QoL scores compared with the Lobectomy group (β 0.17, CI 0.02-0.33, p = 0.029). Although baseline QoL scores favored the AS group significantly (7.1 ± 1.2 vs. 6.7 ± 1.2, p < 0.001), no significant difference was observed after 12 months (7.2 ± 1.2 vs. 7.1 ± 1.2, p = 0.592). Conclusions: This study demonstrated that age, tumor size, family history of thyroid cancer, awareness of AS, and income were associated with patients' treatment choices. Although the overall QoL scores were significantly higher in the AS group, the QoL became similar between the two groups after 12 months. Clinical Trial Registration: KCT0004935.

A newly developed, easy-to-use prehospital drug-derived score compared with three conventional scores: A prospective multicenter study.

The use of medications by emergency medical services (EMS) is increasing. Conventional scores are time-consuming and therefore difficult to use in an emergency setting. For early decision-making, an easy-to-use score based on the medications administered by the EMS may have prognostic value. The primary objective of this study was to develop the prehospital drug-derived score (PDDS) for 2-day mortality. A prospective, multicenter, ambulance-based cohort study was conducted in adults with undifferentiated acute diseases treated by EMS and transferred to the emergency department. Demographic data, prehospital diagnosis data, prehospital medication and variables for the calculation of the National Early Warning Score 2 (NEWS2), Rapid Emergency Medicine Score (REMS), and Rapid Acute Physiology Score (RAPS) were collected. The PDDS was developed and validated, establishing three levels of risk of 2-day mortality. The predictive capability of each score was determined by the area under the curve of the receiver operating characteristic curve (AUROC) and compared using the Delong's test (p-value). A total of 6401 patients were included. The PDDS included age and the use of norepinephrine, analgesics, neuromuscular blocking agents, diuretics, antihypertensive agents, tranexamic acid, and bicarbonate. The AUROC of PDDS was .86 (95% CI: .816-.903) versus NEWS2 .866 (95% CI: .822-.911), p = .828; versus REMS .885 (95% CI: .845-.924), p = .311; versus RAPS .886 (95% CI: .846-.926), p = .335, respectively. The newly developed easy-to-use prehospital drug-derived PDDS score has an excellent predictive value of early mortality. The PDDS score was comparable to the conventional risk scores and therefore might serve as an alternative score in the prehospital emergency setting.

Effectiveness of neck-specific exercises with and without internet-based support on dizziness/unsteadiness in chronic whiplash-associated disorders: Secondary analyses of a randomised controlled trial.

To investigate the effectiveness in individuals with chronic whiplash-associated disorders (WADs) of neck-specific exercise (NSE) supervised by a physiotherapist twice a week for 12 weeks versus neck-specific exercise with internet support and four physiotherapy visits (NSEIT) regarding dizziness, unsteadiness and balance, and to investigate the differences between WAD grades. This is a secondary analysis of a prospective randomised multicentre study (RCT) with concealed allocation (ClinicalTrials.gov Protocol ID: NCT03022812). The outcomes were dizziness measured on the Dizziness Handicap Inventory (DHI); dizziness at rest and during activity and unsteadiness using visual analogue scales; and standing on one leg with eyes closed (SOLEC). Participants (n = 140) were randomised to NSE or NSEIT. Measurements were obtained at baseline, and at three- and 15-month follow-ups by assessor-blinded investigators. There were no significant differences between NSEIT and NSE in any of the outcomes (p>0.38). Both NSEIT and NSE improved over time (p<0.02; effect size (ES) = 0.74-1.01) in DHI score and dizziness during activity. There was a significant group-by-time interaction effect in dizziness (at rest: p = 0.035; ES: 0.66; and during activity: p = 0.016; ES: 1.24) between WAD grades. Individuals with WAD grade 3 had dizziness/unsteadiness to a greater extent and improved in all outcomes over time (p<0.04) compared to those with WAD grade 2, except for SOLEC. There were no significant group differences between NSEIT and NSE. Both groups decreased in terms of self-reported dizziness (DHI, dizziness during activity), with medium to large effect size. Those with WAD grade 3 have dizziness/unsteadiness to a greater extent than those with WAD grade 2. Despite improvements, many participants still reported dizziness at 15-month follow-up, and additional balance training and/or vestibular exercise may be investigated for potential additional effect.

The self-correction and influence factors of congenital auricular deformity: A prospective cohort study.

To prospectively observe the self-correction of congenital auricular deformity (CAD) and explore the potential factors affecting the self-correction. This study was a multi-center prospective observational study. Newborns aged 0-3 days from 12 Maternal and Child Health Hospitals or Maternity Hospitals were chosen as the participants and prospectively followed up until week 6 after birth. The primary and secondary outcome was the score of deformity, and the secondary outcome was the improvement rate, respectively. A total of 135 newborns diagnosed with CAD (237 ears) were recruited. Boys and girls accounted for 50.37% (117 ears) and 49.63% (120 ears). The top morphological type was the constricted ear (107 ears, 45.15%). The score of deformity at baseline, week 3, and week 6 after enrollment was 4.00, 3.00, and 2.00, decreasing over time (P < 0.05). The higher the severity of deformity, the worse the self-correcting effect (P < 0.05). The scores of deformity of Stahl's ear were lower than those of others after follow-up (P < 0.05). No significant differences among the scores of deformity in different genders (P >0.05). The total improvement rate at week 3 and week 6 was 29.96% (71/237 ears) and 37.13% (88/237), respectively. The improvement rate of the Stahl's ear at week 3 and week 6 after enrollment was higher than that of four other morphological types (P < 0.05). Some CAD tends to self-correction, but for most CADs, there is still a need for early correction. Morphological types and severity of deformity are the main influencing factors on self-correcting effect, whereas sex was not.

Trajectories and predictors of suicidal ideation in clinical characteristics and pharmacological treatments for major depressive disorder: a study based on a national multi-centered prospective cohort

Suicidal ideation (SI) is a significant precursor and risk marker for suicide behaviors in major depressive disorder (MDD). Exploration of SI trajectory from a longitudinal framework are essential for treatment guidelines and clinical management of suicide risk. This study sought to explore SI trajectories and its associated clinical, sociodemographic characteristics, and initial treatment among patients with MDD. We used data from a non-interventional, national multi-centered prospective cohort study. 1 461 patients with MDD were included in the growth mixture modeling using SI at baseline, 2 weeks, 4 weeks, 8 weeks, 12 weeks, and 6 months, 9 months, and 12 months as the indicator. A multinomial regression was employed with SI trajectory as the outcome and anhedonia, depressive symptoms, atypical depressive symptoms, pharmacological treatments, and other covariates as the predictors. Four distinct SI trajectories were identified: a consistently low SI trajectory(50.7%), a persistently mild SI trajectory(20.6%), a fast declined SI trajectory(8.9%), and a slowly declined trajectory(19.8%). Compared to those with a consistently low SI trajectory, a higher score of anhedonia was associated with an increased risk of experiencing persistently mild (RRR = 1.20, 95%CI: 1.05, 1.38) and slowly declined SI (1.54, 95%CI: 1.32, 1.80). Severity of depressive symptom was also positively associated with the risk of experiencing persistently mild (1.15, 95%CI: 1.13, 1.18) and slowly declined SI (1.17, 95%CI: 1.14, 1.21). And the risk of experiencing slowly declined SI was higher for those use SSRI(1.49, 95%CI: 1.02, 2.31), and for those use antidepressant and antipsychotic/mood stabilizer combined therapy (3.78, 95%CI: 1.48, 9.61). The findings of this study are potentially useful for clinical practice as critical indicators of profiles and interventions for prognosis among patients with MDD. Further research is warranted to explore potential modifiable factors and the association between SI trajectories and suicide behavior.

Modified notching classification in inverted-bearing and conventional-bearing reverse total shoulder arthroplasty.

Scapular notching is a common complication of reverse total shoulder arthroplasty (RTSA). Although the notching rate has reduced significantly thanks to modifications to the surgical technique and humeral and glenoid components, uncontrollable polyethylene (PE)-induced osteolysis can still occur. In contrast to conventional-bearing (CB-RTSA), inverted-bearing RTSA (IB-RTSA) systems, with PE glenospheres and metal or ceramic humeral liners, avoid PE abrasion through scapulohumeral contact. If present, the resulting notch has a different size and configuration than with CB-RTSA. Thus, a modified notching classification seems reasonable. Even in CB-RTSA, the early stages of notching show a different configuration than implied by the established Nerot-Sirveaux classification; therefore, a modification of the classification system is recommended. In a prospective multicentre study, 250 cases underwent IB-RTSA. Of these, 39 died, and 28 were lost to follow-up for other reasons, leaving 183 shoulders for the final follow-up examination at a mean of 120.7months (range 84.1-172.4months). In the CB-RTSA group, we retrospectively evaluated radiographs of 59 consecutive patients with a follow-up ranging from 2 to 7years. We analysed the appearance, evolution over time, and location of bone loss on the scapular neck according to the modified Nerot-Sirveaux classification. In IB-RTSA, notching resulted in a new morphological configuration: In contrast to the Nerot-Sirveaux classification, notching began far from the baseplate as an impression or abrasion of the humeral component in the inferior scapular rim. Due to simultaneous mechanical ablation, the defect gradually enlarged, but usually did not contact the baseplate or extend beyond the inferior peg. No signs of PE-induced osteolysis were found. The notching rate reached 19% after 2years and approached 36% after 10years. Most shoulders had grade 0 notching (64%), followed by grade 1 (29%); extensive erosion (grade 4) was not observed. In the CB-RTSA group, a small bony impression or erosion without signs of PE-induced osteolysis was observed medial to the scapular neck, without contact with the metaglene in the early phase, which was similar to the impression of the humeral component in IB-RTSA. The notching rate was 86% for CB-RTSA. A new classification was developed for IB-RTSA, which corresponds to the pathophysiological processes and is compatible with the existing Nerot-Sirveaux classification. Bone erosion in CB-RTSA is not adequately represented by the established classification in the early stages. For this reason, a supplement to the existing classification is presented. Level 4, Case Series, Treatment Study.

Cost-Utility Analysis of PCSK9 Inhibitors and Quality of Life: A Two-Year Multicenter Non-Randomized Study.

The primary objective of this study was to conduct a cost-utility analysis of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in real-world, comparing their use with standard care for managing cardiovascular disease. A multicenter prospective study was conducted across 12 Spanish hospitals from May 2020 to April 2022, involving 158 patients with hypercholesterolemia or atherosclerotic cardiovascular disease. This study assessed health-related quality of life (QoL) using the EQ-5D-3L questionnaire. The cost-utility analysis evaluated the economic impact of PCSK9 inhibitors when used with standard care compared to standard care alone, calculating the incremental cost-effectiveness ratio (ICER). This study included 158 patients with an average age of 61 years, male (66.5%). For patients initiating PCSK9 inhibitors, the treatment cost was EUR 13,633.39, while standard therapy cost EUR 3638.25 over two years. QoL for PCSK9 inhibitors stood at 1.6489 over two years, compared to 1.4548 for standard therapy. The results revealed favorable cost-utility outcomes, with an ICER of EUR 51,427.72. Significant improvements were observed in the domains of mobility, self-care, daily activities, pain/discomfort, and anxiety/depression (p < 0.001). This study presents the first real-world cost-utility analysis of PCSK9 inhibitors, supporting their economic rationale and highlighting their benefits in clinical practice. Healthcare decision-makers can use these results to inform their decisions and reimbursement policies concerning PCSK9 inhibitors. Trial Registration clinicaltrials.gov Identifier: NCT04319081.

Modern CRRT systems are associated with lower risk of hypothermia.

One risk of continuous renal replacement therapy (CRRT) is inadvertent hypothermia (IH), which is defined as a non-therapeutic core temperature decrease below normal. In continuous renal replacement therapy, heat loss will always occur from blood pumped through the dialysis circuit to cooler environment, predisposing for hypothermia. Blood flow and effluent flows are the most important parameters causing heat loss. We investigated and compared the novel TherMax warmer to previous generation technologies during CRRT in a multicenter setting. This was a prospective observational multicenter study with historic single-center controls. The study group consisted of 100 patients in eight Swedish ICUs with clinical indication for CRRT, using the PrisMax platform and TherMax warmer. Both patient and set warmer temperatures were recorded hourly for the first 24h. The presence of treatment hours in hypothermia (< 36.0 Celsius) and the difference between set warmer temperature and measured patient temperature in the multi-center study cohort were compared to a matched single-center historic control cohort treated with the old Prismaflex platform and adjacent Barkey warmer. In the TherMax group 77/100 (77.0%) of patients, and for controls 26/86 (30.2%) of patients were free of hypothermia (Chi square, p < 0.001). The mean number of hours spent in hypothermia was (mean ± SD) 0.66 ± 1.60 and 6.92 ± 7.79h in the TherMax and control groups, respectively (Chi square p < 0.001).In the study group the patient temperature was higher than the set temperature on the warmer with a difference of Δ0.47 ± 0.80°C (minor difference), whereas in the control group the set temperature on the warmer was higher than the patient temperature with a difference of Δ4.55 ± 1.00°C (over-correction).The novel TherMax warmer technology protected against hypothermia and was significantly more accurate than the Barkey warmer.

6973 Prospective Multicenter Registry-Based Study on Thyroid Storm: The 2016 Guidelines for the Management from the Japan Thyroid Association and Japan Endocrine Society Are Useful

Abstract Disclosure: Y. Furukawa: None. K. Tanaka: None. O. Isozaki: None. A. Suzuki: None. T. Iburi: None. K. Tsuboi: None. M. Iguchi: None. N. Kanamoto: None. K. Minamitani: None. S. Wakino: None. T. Satoh: None. S. Teramukai: None. E. Kimura: None. Y. Miyake: None. T. Akamizu: None. Context: The mortality rate in thyroid storm (TS) has been reported to be higher than 10%. Even when patients survive, some have irreversible damages. In order to improve the prognosis of patients with TS, appropriate management as well as prompt and accurate diagnosis are needed. We created the diagnostic criteria in 2012 and established guidelines for the management of TS in 2016. Objective: We aimed to evaluate the effectiveness of the 2016 guidelines for the management of TS proposed by the Japan Thyroid Association and Japan Endocrine Society. Design: Prospective registry-based study through a secure web platform. Setting: Prospective multicenter registry. Patients and Measurements: Patients with new-onset TS were registered in the Research Electronic Data Capture (REDCap) from May 1, 2018 to April 30, 2022, over four years. On day 30 after admission, clinical information and prognosis of each patient were added to the platform. On day 180, the prognosis was described. The questionnaire consisted of 176 items totally. Results: This study included 110 patients with TS (93 definite and 17 suspected). The median of Acute Physiology and Chronic Health Evaluation (APACHE) II score was 13, higher than the score in the previous nationwide survey, 10 (p=0.001). Nonetheless, the mortality rate at day 30 was 5.5%, approximately half compared with 10.7% in the previous nationwide survey (p=0.13). Lower BMI, lower left ventricular ejection fraction (LVEF) and shock were positively associated with poor prognosis at day 30. The lack of fever ≥ 38°C was surprisingly associated to the outcome. Approximately 80% of doctors followed the guidelines. The mortality rate in patients with an APACHE II score ≥ 12 for whom the guidelines were not followed was significantly higher than the rate in patients for whom the guidelines were followed (50% vs. 4.7%) (p=0.01). Conclusions: Prognosis seemed better than in the previous nationwide survey, even though disease severity was higher. The mortality rate was lower when the guidelines were followed. Thus, the guidelines are useful for managing TS. Presentation: 6/2/2024

12200 Impact Of Strict IGF-1 Control (I-Con) On Quality Of Life Scores In Patients With Acromegaly

Abstract Disclosure: C. Gandhi: None. C.L. Chik: Advisory Board Member; Self; Ipsen, Novo Nordisk, Novartis Pharmaceuticals. Grant Recipient; Self; Pfizer, Inc.. J.A. Rivera: None. M. Denis: None. S. Van Uum: Advisory Board Member; Self; Ipsen, Pfizer, Inc., Novo Nordisk, Spruce. D.T. Holmes: Other; Self; Roche Diagnostics. S.Z. Ezzat: Advisory Board Member; Self; Bayer, Inc., Eli Lilly &amp; Company, Ipsen, Novartis Pharmaceuticals, Merck, Eisai. Objective: Examine, in a real world setting, whether strict normalization of modestly elevated IGF-1 can result in clinical and health-related quality of life benefits in patients with acromegaly in a prospective 6-month multicenter interventional study. Methods: Strict IGF-1 control was achieved by the addition or dose optimization of pegvisomant (PEGV) in acromegaly patients with modest elevation of IGF-1 levels (&amp;gt;100% and &amp;lt;150% of upper limit of normal [%ULN]). IGF-1 measurements were completed in a designated central laboratory, initially using the IDS-iSYS and after the first four patients with the Roche Elecsys® method. The transition did not impact study results. Clinical and biochemical parameters were assessed at baseline, 1 and 3 months for dose titration of PEGV and at 6 months. The Patient-Assessed Acromegaly Symptom Questionnaire (PASQ), the Acromegaly Quality of Life questionnaire (AcroQoL) and the Acromegaly Disease Activity Tool (ACRODAT®) were completed at baseline and at 6 months. Results: Ten patients (8 males, mean age at screening 50.7 ± 11.3 years) from four centers across Canada participated in the study. Age at diagnosis was 43.9 ± 12.1 years and all patients had macrotumors. Nine patients had prior transsphenoidal surgeries including one with adjunct radiation therapy. All 10 patients had trials of somatostatin analogs (SSA) and SSA was switched to PEGV in two patients because of lack of efficacy. At the time of screening, six patients were on SSA, two on PEGV, and two on SSA and PEGV. At six months, the mean daily dose of PEGV increased from 7.5 ± 12.3 mg (range 0 to 30 mg daily) to 17.6 ± 13.7 mg (range 5 to 40 mg daily). After six months of dose escalation or the addition of PEGV, IGF-1 decreased from 258.5 ± 59.2 µg/L (121.8 ± 14.4 %ULN) to 184.1 ± 41.1 µg/L (86.6 ± 20.0 %ULN) (p=0.001). The summation of PASQ1 to PASQ6 score decreased from 14.6 ± 10.7 to 11.1 ± 8.9 (p=0.02); however there was no statistically significant difference in the AcroQoL score (63.8 ± 24.0 vs 66.5 ± 22.6, p=0.11). The ACRODAT® overall status decreased from 84.3 ± 27.6 to 33.8 ± 17.1 (p=0.001) and there was a decline in the summation of the tumor status, comorbidities, symptoms and health-related qualify of life impairment score (7.1 ± 1.8 vs 6.4 ± 1.8, p=0.02). Hemoglobin A1c, fasting lipids, liver enzymes and renal function were not significantly affected. Repeat MRI of the sella at 6 months showed no change. Conclusions: In spite of the small number of patients participating in this study, strict control in patients with a modest IGF-1 elevation was accompanied by clinical improvements detected by the PASQ and ACRODAT®. Our results support the notion that strict IGF-1 control can be accompanied by improvement in clinical symptoms with lower PASQ scores. These findings need to be confirmed in a larger scale clinical trial. Presentation: 6/2/2024

6877 Withdrawing Growth Hormone Treatment at Mid-Puberty in Idiopathic Isolated Growth Hormone Deficiency: Baseline Characteristics in Patient-Preference Design Study

Abstract Disclosure: J. Vliegenthart: None. J. Wit: None. B. Bakker: None. A. Boot: None. C. de Bruin: None. M. Finken: None. J.V. Heyden: None. M. Houdijk: None. H. van der Kamp: None. E. Van Mil: None. A. Reedijk: None. T. Sas: None. D.A. Schott: None. P. van Setten: None. S. Straetemans: None. V. van Tellingen: None. B. Touwslager: None. A.V. Trotsenburg: None. P. voorhoeve: None. A.C. Hokken-Koelega: None. D.C. van der Kaay: None. Background: The majority of children diagnosed with idiopathic isolated growth hormone deficiency (IIGHD) show a normal growth hormone (GH) secretion (assessed by GH stimulation tests) when retested at near adult height (NAH). It appears plausible that, if normal stimulated GH secretion is observed in mid-puberty, continuing recombinant human GH (rhGH) treatment may only have a minor effect on NAH. The effect on NAH has never been investigated in a prospective study. Aim: To evaluate patient preference in the choice to (dis-)continue GH treatment from mid-puberty, and to study whether patients who discontinued treatment differed in baseline characteristics from those who continued treatment. Methods: The study population consisted of adolescents who were diagnosed in childhood with IIGHD (GH peak at diagnosis between 1.7 ug/L and 10 ug/L) and who had started rhGH therapy between 2005-2018. According to the national treatment protocol, GH secretion was retested in mid-puberty (males: Tanner stage G3/4, testicular volume &amp;gt;12 ml and bone age (BA) 13-16 years; females: Tanner stage B3/4 and BA 11-14 years). In this multicentre prospective patient-preference design study, adolescents who tested GH sufficient at mid-puberty (GH peak &amp;gt;6.7 ug/L) had the choice to discontinue or continue rhGH treatment until NAH (height velocity &amp;lt;2cm/year). Results: In total 127 patients (95 male, 75%) participated in this study. Forty-four patients (35%) chose to continue GH treatment until NAH (group 1), and 83 patients (65%) chose to discontinue GH treatment (group 2). Mean height at inclusion (group 1: -0.76±0.69 SDS vs group 2: -0.47±0.85 SDS; P=0.055), target height SDS (group 1: -0.73±0.54 SDS and -0.58±0.53 SDS, P=0.15) and age at inclusion (group 1: 14.0±1.1y and 13.9±1.1y, P=0.69) did not significantly differ between groups. Males and females did not differ in these characteristics. Currently, 109 patients (86%) have reached NAH. Conclusions: The majority of patients (65%) preferred to discontinue rhGH treatment after sufficient GH retesting in mid-puberty. An anticipated difference in baseline data between the groups (adolescents who choose to discontinue treatment may be taller and older) could not be confirmed. Data are being collected until all patients reach near adult height. Presentation: 6/3/2024

9262 Withdrawing Growth Hormone Treatment at Mid-Puberty in Idiopathic Isolated Growth Hormone Deficiency: Baseline Characteristics in Patient-Preference Design Study

Abstract Disclosure: J. Vliegenthart: None. J. Wit: None. B. Bakker: None. A. Boot: None. C. de Bruin: None. M. Finken: None. J.V. Heyden: None. M. Houdijk: None. H. van der Kamp: None. E. Van Mil: None. A. Reedijk: None. T. Sas: None. D.A. Schott: None. P. van Setten: None. S. Straetemans: None. V. van Tellingen: None. B. Touwslager: None. A.V. Trotsenburg: None. P. voorhoeve: None. A.C. Hokken-Koelega: None. D.C. van der Kaay: None. Background: The majority of children diagnosed with idiopathic isolated growth hormone deficiency (IIGHD) show a normal growth hormone (GH) secretion (assessed by GH stimulation tests) when retested at near adult height (NAH). It appears plausible that, if normal stimulated GH secretion is observed in mid-puberty, continuing recombinant human GH (rhGH) treatment may only have a minor effect on NAH. The effect on NAH has never been investigated in a prospective study. Aim: To evaluate patient preference in the choice to (dis-)continue GH treatment from mid-puberty, and to study whether patients who discontinued treatment differed in baseline characteristics from those who continued treatment. Methods: The study population consisted of adolescents who were diagnosed in childhood with IIGHD (GH peak at diagnosis between 1.7 ug/L and 10 ug/L) and who had started rhGH therapy between 2005-2018. According to the national treatment protocol, GH secretion was retested in mid-puberty (males: Tanner stage G3/4, testicular volume &amp;gt;12 ml and bone age (BA) 13-16 years; females: Tanner stage B3/4 and BA 11-14 years). In this multicentre prospective patient-preference design study, adolescents who tested GH sufficient at mid-puberty (GH peak &amp;gt;6.7 ug/L) had the choice to discontinue or continue rhGH treatment until NAH (height velocity &amp;lt;2cm/year). Results: In total 127 patients (95 male, 75%) participated in this study. Forty-four patients (35%) chose to continue GH treatment until NAH (group 1), and 83 patients (65%) chose to discontinue GH treatment (group 2). Mean height at inclusion (group 1: -0.76±0.69 SDS vs group 2: -0.47±0.85 SDS; P=0.055), target height SDS (group 1: -0.73±0.54 SDS and -0.58±0.53 SDS, P=0.15) and age at inclusion (group 1: 14.0±1.1y and 13.9±1.1y, P=0.69) did not significantly differ between groups. Males and females did not differ in these characteristics. Currently, 109 patients (86%) have reached NAH. Conclusions: The majority of patients (65%) preferred to discontinue rhGH treatment after sufficient GH retesting in mid-puberty. An anticipated difference in baseline data between the groups (adolescents who choose to discontinue treatment may be taller and older) could not be confirmed. Data are being collected until all patients reach near adult height. Presentation: 6/3/2024

12315 Unveiling A Paraganglioma: Catecholamine-Induced Hyperglycemia Masquerading As Type 2 Diabetes Mellitus

Abstract Disclosure: S. Salman: None. M. Hussine: None. J. Tibaldi: None. Background: Excessive catecholamines have been demonstrated to exert adverse effects on insulin homeostasis and carbohydrate metabolism, potentially resulting in the onset of secondary DM. We present a case of a patient who had been previously misdiagnosed with T2DM for an extended period. Clinical Case: A 34-year-old woman with history of T2DM, HTN, and chronic tachycardia on beta blockers, presented with complaints of palpitations, headaches, and abdominal pain for two weeks. Upon admission, she was found to be in DKA, necessitating transient administration of insulin drip. Furthermore, she exhibited persistent tachycardia and intermittent episodes of hypertensive urgency. Notably, thyroid levels revealed euthyroidism. Although DKA resolved, her fasting blood sugar levels remained elevated and refractory to escalating insulin therapy. CT abdomen with contrast revealed a large enhancing mass in the RUQ. MRI abdomen confirmed an 8.1 cm heterogeneously enhancing T2 hyperintense mass located in the RUQ, abutting the right hepatic lobe, right adrenal gland, extrahepatic biliary ducts, and adjacent vessels. Given suspicions of a neuroendocrine tumor, she was transferred to the surgical service for tumor excision. Hormonal analysis revealed elevations in plasma metanephrines (620 pg/mL, n 0-88 pg/mL), plasma normetanephrines (9954 pg/mL, n 0-210.1 pg/mL), 24-hr urine normetanephrines (10,952 μg/24hr, n 110-720 μg/24hr) and 24-hr urine metanephrines (1406 μg/24hr, n 35-278 μg/24hr). Additionally, she exhibited elevated 24-hr urine epinephrine fraction (218 μg/g Cr, 0-20 μg/g Cr) and 24-hr urine norepinephrine fraction (2775 μg/g Cr, 0-45 μg/g Cr). Preoperatively, appropriate alpha and beta blockade were administered, followed by successful retroperitoneal tumor resection. Postoperatively, her glucose levels normalized without the need for further insulin therapy, and no episodes of hypoglycemia were reported. Histopathological examination of the excised mass revealed an 11 cm sympathetic paraganglioma with retention of SDHB staining. Genetic testing for SDHB, SDHD, VHL, and RET mutations is pending. Conclusion: This case underscores the potential oversight of pheochromocytomas and paragangliomas due to their nonspecific symptomatology, often mimicking more prevalent conditions, thereby presenting diagnostic challenges. The catecholamines secreted by these tumors can lead to both impaired insulin secretion and increased insulin resistance, resulting in clinically significant manifestations. The exact mechanism underlying the glycemic dysregulation remains controversial, necessitating further investigation through large-scale multicenter prospective studies to enhance understanding and inform diagnostic and therapeutic strategies for these tumors, which can manifest with severe and potentially fatal glycemic disturbances. Presentation: 6/1/2024

Pulmonary fibrosis followed by severe pneumonia in patients with COVID-19 infection requiring mechanical ventilation: a prospective multicentre study

BackgroundsThe management of lung complications, especially fibrosis, after COVID-19 pneumonia, is an important issue in the COVID-19 post-pandemic era. We aimed to investigate risk factors for pulmonary fibrosis development in...

Long-Term Outcome of a Multicenter Prospective Study on Efficacy and Safety of High-Dose Stereotactic Body Radiation Therapy ≥48-h Interfraction Interval for ≤5 cm Hepatocellular Carcinoma

Introduction: The goal of this study was to evaluate the efficacy and safety of high-dose stereotactic body radiation therapy (SBRT) with an extended (48 h or more) interfraction interval for hepatocellular carcinoma (HCC) ≤5 cm in size after incomplete response to transarterial chemoembolization (TACE). Methods: This multicenter prospective study included 54 patients with inoperable HCC of ≤5 cm size between July 2012 and June 2015. A total SBRT dose of 60 Gy in 3 fractions was administered within 14 days with ≥48-h interfraction interval to patients who showed an incomplete response after 1–5 sessions of TACE. Treatment responses were defined according to the modified Response Evaluation Criteria for Solid Tumors. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Results: Forty-eight patients were evaluated with a median follow-up period of 66 months (range, 2–126 months). The median tumor size was 2.0 cm (range, 1.0–4.5 cm), and most patients (87.5%) had a single lesion. The 1-, 2-, and 5-year local control (LC) rates were 100%, 94.8%, and 90.7%, respectively. The 1-, 2-, and 5-year progression-free survival (PFS) rates were 63.4%, 56.9%, and 24.9%, respectively. The 1-, 2-, and 5-year overall survival (OS) rates were 95.6%, 90.9%, and 76.5%, respectively. None of the patients experienced grade 3+ gastrointestinal toxicity, while 1 patient developed non-classic radiation-induced liver disease 2 months after SBRT. Conclusion: High-dose SBRT with a ≥48-h interfraction interval after incomplete response to TACE is effective for HCC ≤5 cm in size as evidenced by the high rates of LC and OS and acceptable treatment-related toxicity.

Prospective Multicenter Screening With High-Sensitivity Cardiac Troponin T for Wild-Type Transthyretin Cardiac Amyloidosis in Outpatient and Community-Based Settings.

High-sensitivity cardiac troponin T (hs-cTnT) was proposed as a simple and useful diagnostic tool for cardiac amyloidosis (CA). We performed exploratory systemic screening using hs-cTnT to detect wild-type transthyretin CA (ATTRwt-CA) in outpatient and community-based settings. This study was a prospective multicenter study including 8 internal medicine clinics in Kochi Prefecture, Japan. Consecutive individuals aged ≥70 years who visited those clinics as outpatients were enrolled. Patients with a prior diagnosis of CA or a history of heart failure hospitalization were excluded. We measured hs-cTnT levels in the enrolled individuals at each clinic, and those with elevated hs-cTnT levels (≥0.03ng/mL) received further detailed examination, including remeasurement of hs-cTnT. The diagnosis of ATTRwt-CA was confirmed by biopsy-proven transthyretin. Of 1,141 individuals enrolled in the study, 55 (4.8%) had elevated hs-cTnT levels. Of the 33 patients who underwent further examination, 22 had elevated hs-cTnT levels at remeasurement. Finally, 2 men were diagnosed with ATTRwt-CA. The prevalence of ATTRwt-CA was 9.1% (2/22) among patients with elevated hs-cTnT levels at two examinations, and at least 0.18% (2/1,141) in the whole study population. Measurement of hs-cTnT will help to screen for patients with undiagnosed ATTRwt-CA in primary care practice.

The association between serum S100β levels and prognosis in acute stroke patients after intravenous thrombolysis: a multicenter prospective cohort study

BackgroundS100β is a biomarker of astroglial damage, the level of which is significantly increased following brain injury. However, the characteristics of S100β and its association with prognosis in patients with acute ischemic stroke following intravenous thrombolysis (IVT) remain unclear.MethodsPatients in this multicenter prospective cohort study were prospectively and consecutively recruited from 16 centers. Serum S100β levels were measured 24 h after IVT. National Institutes of Health Stroke Scale (NIHSS) and hemorrhagic transformation (HT) were measured simultaneously. NIHSS at 7 days after stroke, final infarct volume, and modified Rankin Scale (mRS) scores at 90 days were also collected. An mRS score ≥ 2 at 90 days was defined as an unfavorable outcome.ResultsA total of 1072 patients were included in the analysis. The highest S100β levels (> 0.20 ng/mL) correlated independently with HT and higher NIHSS at 24 h, higher NIHSS at 7 days, larger final infarct volume, and unfavorable outcome at 3 months. The patients were divided into two groups based on dominant and non-dominant stroke hemispheres. The highest S100β level was similarly associated with the infarct volume in patients with stroke in either hemisphere (dominant: β 36.853, 95% confidence interval (CI) 22.659–51.048, P < 0.001; non-dominant: β 23.645, 95% CI 10.774–36.516, P = 0.007). However, serum S100β levels at 24 h were more strongly associated with NIHSS scores at 24 h and 3-month unfavorable outcome in patients with dominant hemisphere stroke (NIHSS: β 3.470, 95% CI 2.392–4.548, P < 0.001; 3-month outcome: odds ratio (OR) 5.436, 95% CI 2.936–10.064, P < 0.001) than in those with non-dominant hemisphere stroke (NIHSS: β 0.326, 95% CI − 0.735–1.387, P = 0.547; 3-month outcome: OR 0.882, 95% CI 0.538–1.445, P = 0.619). The association of S100β levels and HT was not significant in either stroke lateralization group.ConclusionsSerum S100β levels 24 h after IVT were independently associated with HT, infarct volume, and prognosis in patients with IVT, which suggests the application value of serum S100β in judging the degree of disease and predicting prognosis.

First clinical evaluation of a flexible digital ureteroscope with direct in scope suctioning system (Pusen DISS 7.5Ch): prospective multicentric feasibility study.

A new digital single-use flexible ureteroscope, Pusen direct in scope suction (DISS) 7.5Fr (PU3033AH), was evaluated with respect to manoeuvrability, suction quality, visibility and clinical efficiency. A prospective cohort study was conducted in six tertiary reference centers in Europe and Asia between February-April 2024. Adult patients who underwent flexible ureteroscopy and laser lithotripsy (fURSL) for urolithiasis were included. Demographic, intraoperative and follow-up characteristics were recorded. Quality parameters were rated by each surgeon using a Likert scale. a total of 57 fURSL were performed. Preoperative characteristics revealed a mean stone volume of 480.00mm3 (mean Hounsfield Unit- 998). 57.9%(n = 33) of the patients were pre-stented, and a ureteric access sheath was used in 64.9%(n = 37). Integrated-suction was deemed helpful in 94.7%(n = 54) fURSL as reported by the operators. An initial stone free rate (SFR) confirmed by postoperative imaging was achieved in 84.21%(n = 48). Quality parameters of the scope reached a mean Likert score of 4.5, with a "very good" mean evaluation for "scope placement", "visual quality", "irrigation", "deflection", "manoeuvrability", and "weight". "Suction quality" and "overall performance satisfaction" were rated "good". Comparing the Pusen DISS scope with other previously used scopes, overall satisfaction was rated 4.1. When asked if the surgeons would be willing to use the Pusen DISS 7.5Fr scope in the future, all the six surgeons answered positively. The DISS 7.5 Pusen ureteroscope displayed good visibility, manoeuvrability and suction quality, with excellent operative results. Further evaluation with larger comparative cohorts will help understand the potential of in-vivo use of integrated suctioning systems for fURSL.