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Abstract BACKGROUND Most meningiomas are considered benign tumors, however, a subset of meningiomas are characterized by a more aggressive clinical course and require multimodal treatment. Beyond surgery and radiation, there are no effective medical treatments available. Somatostatin receptor 2 (SSTR2) is expressed by the majority of meningiomas. [177Lu]Lu-DOTA-TATE (177Lu-Dotatate) is a SSTR2-targeting radioligand therapeutic agent that has been successful in other oncological entities, including neuroendocrine tumors. Here we report the results of a phase 2 clinical trial (NCT03971461) evaluating 177Lu-Dotatate in patients with advanced and treatment-refractory intracranial meningiomas. METHODS In this multicenter, open-label, phase 2 study, adults with advanced intracranial meningiomas received 177Lu-Dotatate at 7.4 GBq (200 mCi) every eight weeks for four doses. [68Ga]Ga-DOTA-TATE (68Ga-Dotatate) PET was performed before and at the end of treatment. The primary endpoint was progression-free survival at 6 months (PFS-6). Correlative studies evaluated the association of PFS-6, objective response rate, progression-free survival, overall survival with radiographic tumor measurements, and 68Ga-Dotatate uptake on PET. RESULTS Thirty-two patients (F=21, M=11) with progressive meningiomas (WHO 1=7, WHO 2=24, WHO 3=1) were enrolled. Median age was 65.5 (range 41-78) years. All patients previously underwent tumor resection and at least one course of radiation. Three patients (9%) had received medical therapy. Treatment with 177Lu-Dotatate was well tolerated, no treatment-limiting toxicities were observed. Of 29 evaluable patients at the data cutoff, 19 patients (66%) had achieved PFS-6 (WHO 1=4, WHO 2=15). Radiographically, the best response was partial response (PR) in 2 patients (6%) and stable disease (SD) in 20 patients (63%). CONCLUSIONS Treatment with SSTR2-targeting 177Lu-Dotatate is well tolerated and 66% of patients achieved PFS-6, comparing favorably to historical benchmarks, 177Lu-Dotatate therefore may be a useful new therapeutic modality for patients with advanced meningiomas and will be further explored in MOMENTUM-1 (NCT#06955169), an open-label, randomized, phase 2 trial.

Background and aims To validate the applicability of the new histological criteria for autoimmune hepatitis (AIH) proposed by the International AIH Pathology Group (IAIH‐PG) among Chinese patients with AIH and drug‐induced liver injury (DILI). Methods The gold standard for diagnosis relied on clinical response: discontinuing treatment without relapse supported DILI, while relapse or ongoing immunosuppressive treatment confirmed AIH. This two‐centre retrospective cohort study included inpatients with DILI or AIH from January 2002 to March 2023. Cases that underwent liver biopsy were selected according to inclusion and exclusion criteria. The diagnostic performance of the criteria was assessed by an area under the receiver operating characteristic curve (AUROC). Results Out of 69 patients: AIH (41, 59%) and DILI (28, 41%). The accuracy, sensitivity and specificity of the new histological criteria for likely and possible AIH were 70%, 98% and 29%, respectively, with an AUROC of 0.8236 [95% confidence interval (CI): 0.7533–0.8938]. For likely AIH, the accuracy, sensitivity and specificity were 73%, 61% and 89%, respectively, with an AUROC of 0.9177 [95% CI: 0.8757–0.9596]. Moreover, for possible AIH, significant differences were found in serum alanine aminotransferase levels [178.4 (87.0, 435.0) versus 536.5 (206.9, 930.4) U/L] and antinuclear antibody (ANA) ≥1:160 [10 (67%) versus 1 (6%)], as well as in lobular lymphoplasmacytic infiltrate [15 (100%) versus 12 (71%)] and more than mild inflammation [13 (87%)versus 6 (35%)] between AIH and DILI (all P values were <0.05). Conclusion The new histological criteria exhibit good diagnostic efficacy in distinguishing AIH from DILI in China, with high AUROC. Key discriminators include low aminotransferase, ANA ≥1:160, lobular lymphoplasmacytic infiltrate and more than mild inflammation, which may further improve diagnostic accuracy for AIH.

Background: Spontaneous Coronary Artery Dissection (SCAD) is a cause of acute coronary syndrome, particularly among women, and is associated with psychological distress, including depression, anxiety, and post-traumatic stress (PTSD) symptoms. Fibromuscular dysplasia (FMD), a vascular condition that alters the arteries, is often found in patients with SCAD, adding complexity and uncertainty with a second serious diagnosis. This study examined the differences in mental health symptoms between SCAD survivors with and without FMD to better understand their unique psychosocial needs and inform interventions to enhance patient outcomes. Methods: Patients diagnosed with SCAD within the past 3 years were recruited from 6 Canadian cardiac hospitals. Participants completed questionnaires assessing socio-demographics, comorbidities, and validated psychological measures, including Patient Health Questionnaire-9 (PHQ-9) for depression, Generalized Anxiety Disorder-7 (GAD-7) for generalized anxiety, Cardiac Anxiety Questionnaire (CAQ) for cardiac-related anxiety, and PTSD Checklist (PCL-5) for PTSD symptoms. Differences in mental health outcomes between SCAD survivors with and without FMD were analyzed using t-tests for continuous variables and chi-square tests for categorical variables. Results: The study included 326 participants (92.9% female; mean age 53.3 years), with 67 participants (20.6%) having a confirmed diagnosis of FMD at the time of questionnaire completion (39.3% FMD at study completion). Post-SCAD, patients with FMD reported significantly higher scores than patients without FMD on the GAD-7 (6.4±5.9 vs. 4.7±4.9, p = .028), CAQ (29.9±13.1 vs. 26.0±12.3, p = .023), and PCL-5 (17.2±15.4 vs. 13.3± 14.0, p = .048). The proportion of SCAD survivors with FMD scoring in the clinically diagnostic range was significantly higher than those in patients without FMD: 32.8% vs. 20.8% for depression, 31.3% vs. 17.4% for anxiety, 64.2% vs. 49.2% for cardiac anxiety, and 25.4% vs. 11.6% for PTSD (all p < .05). Conclusions: Our findings suggest that SCAD survivors with comorbid FMD experience significantly higher distress —depression, generalized anxiety, cardiac-related anxiety, and PTSD symptoms—compared to those without FMD. Longitudinal research is needed to explore the role of these mental health concerns in long-term mental health and cardiac outcomes. Enhanced psychological interventions for those with FMD may be required.

Abstract Disclosure: A. Nasir: None. F. Dehghani: None. F. Saeidifard: None. M. Ghannam: None. A. Almakadma: None. I. Idries: None. A. Esteghamat: None. R. Nieto- Martinez: None. J.I. Mechanick: None. Background: The Dysglycemia-Based Chronic Disease (DBCD) multi-morbidity care model was developed by American Association of Clinical Endocrinology to address the requirement for preventive care measures to reduce the impact of type two diabetes (T2D ) and its complications. The DBCD model consists of four distinct stages including: insulin resistance, prediabetes, T2D and vascular complication spectrum. This study assesses the prevalence and associated risk factors for each of the four DBCD stages in Iranian adults. Methods: From February 2002 to March 2020, 10,087 participants who attended clinic of Vali-Asr Hospital, Tehran, Iran, were evaluated. In total, 3,465 (34.3%) men with median age of 54.47 years and 6,629 (65.67%) women with median age of 50.2 years were included. A 10 ml blood sample was collected after an overnight fast, centrifuged, and stored at -70°C for lab evaluation to measure fasting blood sugar (FBS). Hemoglobin A1c was measured using high-performance liquid chromatography, while fasting and post-prandial glucose were assessed using enzymatic colorimetric methods. Results: Stage 1 was found in 19.7% of the population (23.2% in women and 13.1% in men), stage 2 in 17.8% of the population (19.3% in women and 14.8% in men), stage 3 in 31.4% of the population (28.2% in women and 37.5% in men), and stage 4 in 21.3% of the population (16.2% in women and 30.9% in men). DBCD stages increased significantly with age (stage 1=43.12, stage 2=51.24, stage 3=54.89, stage 4=61.51, P-value &lt;0.01). All DBCD stages were associated with hypertension (stage 1: OR=3.07, stage 2: OR=5.08 ,stage 3: OR=7.87 and stage 4: OR=17.17) dyslipidemia (stage 1: OR=2.85, stage 2: OR=2.68, stage 3: OR=8.32, and stage 4: OR=7.66)and metabolic syndrome (stage 1: OR=14.04, stage 2: OR=21.95, stage 3: OR=32.50, and stage 4: OR=42.54). Conclusion: The findings of the current study further support the importance of the DBCD model in early detection and prevention of dysglycemia and their associated complications. Presentation: Sunday, July 13, 2025

Abstract Objective To determine the effect of management before and during transplantation on the quality of donated organs. Improvement of preservation methods in cases involving brain death will lead to more effective organ procurement. Methods Data were collected from the 226 brain death cases enrolled in the 12-month study period. All cases, patients with a Glasgow Coma Scale (GCS) score of 3 points, appropriate age, and having medical indications for organ donation, were considered to confirm the criteria of brain death. Transplant outcome data were obtained from the transplant centers. Results The age of the deceased ranged between 1 year and 68 years, with a mean ± SD of 39.54 ± 17.28 years. There was no significant difference between the quality of organs regarding blood group and cause of brain death ( P > 0.05). However, there was a significant difference in the quality of organs regarding age, body mass index (BMI), and gender. There was a significant difference between the level of urea at admission time and procurement time ( P < 0.001), as well as between creatinine level at admission time and procurement time ( P < 0.001). There was also a significant difference between aspartate aminotransferase (AST) at admission time and procurement time ( P < 0.001), and between alanine aminotransferase (ALT) at admission time and procurement time ( P < 0.001). Conclusions Transplant outcomes using older donor livers and kidneys were comparable to those using younger or male donors. These findings provide further evidence that decision-making about organ quality is influenced by age and gender and emphasize the importance of transparency in organ acceptance practices.

Abstract Importance Mesenchymal stromal cells (MSCs) possess therapeutic properties that mediate repair. Obesity impairs MSC functionality and therapeutic efficacy, possibly by eliciting dynamic modifications of epigenetic markers, like 5-hydroxymethylcytosine (5hmC). Objective We hypothesized that human obesity alters the 5hmC landscape and anti-inflammatory capacity of adipose tissue-derived MSCs to activate the prominent inflammatory signaling mediator Interleukin (IL)-1β. Design, Setting, Participants, Intervention Adipose tissue samples were collected from obese and lean individuals (body mass index ≥30 or &lt;30 kg/m2, respectively, n = 11 each) during weight-loss or kidney donation surgery. Main Outcomes and Measures MSCs were harvested and analyzed for 5hmC profiles (MeDIP-seq) and mRNA expression (RNA-seq) (n = 5 each). Subsequently, MSCs or a vehicle were injected into mice, (n = 6 each) and two-weeks later, kidneys were evaluated using in-vivo magnetic resonance imaging and ex vivo studies. The role of IL-1β was then studied in-vitro in MSC-induced immunomodulation using siRNA in macrophages. Results Compared to MSC from lean patients, obese-MSC genes showed 2087 differential 5hmC modifications and 175 differential mRNA expression. Among them, 14 genes with overlapping alterations were involved in regulation of cytokine production, prominently IL-1β. Injecting obese MSCs elevated renal expression of IL-1β and M1 macrophage count but lowered kidney perfusion. Silencing IL-1β in obese-MSCs in vitro reduced M1 phenotype switching in co-incubated macrophages. Conclusions and Relevance Obesity induces epigenetic and gene expression changes in MSCs, particularly in IL-1β, associated with impaired anti-inflammatory functionality of MSCs. Targeting IL-1β could be a useful therapeutic approach to modulate the decline in MSC functionality resulting from obesity.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disorder. It is primarily caused by pathogenic variants in the PKD1 or PKD2 genes. This leads to the development of numerous kidney cysts, which can result in kidney enlargement and progression to kidney failure. Pain is a common symptom in ADPKD and can negatively affect quality of life (QOL). This pain is often due to the continuous growth of kidney and liver cysts or associated cystic complications. We present a case of a 29-year-old woman with ADPKD who experienced chronic, refractory right-sided flank pain that significantly affected her QOL. Her pain persisted despite taking daily multimodal analgesics and undergoing multiple invasive interventions. She had an unusual asymmetric disease with the right kidney accounting for only 24% of her kidney function. After exhausting all other pain control strategies, she underwent right nephrectomy and partial hepatectomy, which led to substantial improvement in pain and QOL. This review describes the causes, manifestations, and management strategies for abdominal and/or flank pain in ADPKD, including a practical stepwise algorithm to guide clinicians in managing pain and improve QOL of patients with ADPKD. Pain in ADPKD can either be acute or chronic and can lead to significant physical and psychologic distress. Effective pain management in ADPKD requires a multidisciplinary approach, incorporating both nonpharmacologic and pharmacologic interventions such as gabapentin or tolvaptan in select cases. Interventions considered in ADPKD pain control include cyst aspiration with sclerotherapy, celiac plexus blockade, spinal cord stimulation, renal denervation, or nephrectomy.