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Abstract Background Cardiac metastasis from neuroendocrine tumors (NET) is rare and has been thought to potentially result in life threatening sequalae. Peptide receptor radionucleotide therapy (PRRT), such as Lutetium-177 (Lu-177) DOTATATE, has been validated as effective treatment for patients with NET who have progressed on somatostatin analogue (SSA) therapy and more recently suggested for use in SAA-naïve higher risk grade 2 and grade 3 NETs. However, Lu-177 DOTATATE therapy has been found to have potentially serious adverse effects both locally and systemically. Overall, the clinical significance of cardiac metastasis of NET, as well as the safety and efficacy of Lu-177 DOTATATE in this cohort, has not been thoroughly evaluated. Purpose This study assessed the outcomes and clinical consequences of cardiac metastatic involvement in patients with NET. Furthermore, this study investigated the safety of Lu-177 DOTATATE therapy in patients with cardiac metastases from NET. Methods All patients who underwent 68Ga-DOTATATE positron emission tomography for evaluation of NET across three tertiary centers between 2016 and 2022 were retrospectively evaluated. Patients with evidence of cardiac metastasis were further evaluated. Baseline characteristics, treatment modality, and clinical outcomes including mortality, arrhythmia or conduction disease, carcinoid heart disease, and heart failure admissions were recorded. Patients with cardiac metastases were grouped and compared based on therapeutic modality (conservative therapy with surveillance or SSA, Lu-177 DOTATATE therapy, or surgical resection of metastases). Results From 3253 patients with NET, 51 patients were identified to have cardiac metastases (mean age 66.7 ± 12.2 years, 54% male). Three patients underwent surgical resection of cardiac metastases, and in two of whom this was concomitant while undergoing valve surgery for carcinoid heart disease. Patients with cardiac metastasis had significantly higher mortality than patients without cardiac metastasis (HR 2.12, 95%CI 1.00 – 4.52, p = 0.049, Figure 1A). Median follow-up from diagnosis of cardiac metastasis was 3.64 years [IQR 1.59 – 5.64]. There was no significant difference in clinical outcomes between patients that received Lu-177 DOTATATE therapy (n = 27) and conservative therapy (n = 21). Specifically, there was no significant difference in mortality risk at five years post the diagnosis of cardiac metastasis between these groups (p = 0.47, Figure 1B). Conclusion Patients with cardiac metastasis from NETs have worse clinical outcomes than NET patients without cardiac metastatic involvement. Lu-177 DOTATATE therapy appears to be safe in patients with cardiac metastasis from NET.Figure 1AFigure 1B

Abstract Introduction Non-cardiovascular end-organ dysfunction is an important determinant of outcomes in cardiac intensive care unit (CICU) patients. We examined the association between in-hospital mortality with the severity and extent of admission liver function test (LFT) abnormalities in a heterogeneous CICU population. Purpose We hypothesized that a greater severity or extent of LFT abnormalities would be associated with higher in-hospital mortality. Methods We included consecutive unique adult CICU patients with available data for one or more of the admission LFT values of interest. Admission laboratory values were defined as those closest to CICU admission. We used the NIH Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 to categorize the severity of each LFT abnormality from Grade 0 (normal) to Grade 4 (life-threatening). We defined the extent of LFT abnormality as the number of individual LFTs meeting criteria for CTCAE Grade 1 or greater. The primary outcome of interest was all-cause in-hospital mortality. Odds ratio (OR) and 95% confidence interval (CI) values for in-hospital mortality were estimated using logistic regression, before and after multivariable adjustment. Results Of 12,428 unique CICU patients, 5,144 were excluded due to a lack of available data for any admission LFT values. The remaining 7,284 patients comprised the final study population. Among patients with available data for each individual LFT, abnormal values were present in: AST, 2,743/5,733 (47.8%); ALT 1,576/5,512 (28.6%); ALK 611/3,684 (16.6%); and TB 898/5,155 (17.4%). A total of 864 (11.9%) patients died during hospitalization. In-hospital mortality was higher for patients with one or more LFTs meeting criteria for CTCAE Grade 1 or greater (17.9% vs. 6.4%, adjusted OR 1.54 [1.27-1.86], p <0.001). A stepwise increase in in-hospital mortality was observed with increasing CTCAE grade, both overall (adjusted OR 1.25 per each higher CTCAE grade [1.16-1.34], p <0.001); (Figure 1A), and for each individual LFT (Figure 1B). Conclusion Cardiohepatic syndrome is an important predictor of prognosis in CICU patients, as the extent and severity of LFT abnormalities are strongly associated with in-hospital mortality. This is the first large-scale study to examine the association between the magnitude of hepatic biomarker derangement with in-hospital mortality in unselected CICU patients. Patients with markedly elevated LFT values exhibited the highest risk of in-hospital mortality. This analysis advocates for the inclusion of commonly obtained LFTs in future risk-prediction tools for enhanced prognostication.

Objectives To identify Reddit users’ viewpoints and inquiries about spinal cord stimulation (SCS) for chronic back pain using Reddit databases. Methods We performed a qualitative analysis of public, anonymous threads and comments from targeted subreddits within the Reddit community. We used the Python Reddit API Wrapper to extract relevant data. A qualitative descriptive approach was employed, using natural language processing to identify and categorize common questions, concerns, and opinions shared by patients regarding SCS. Results Our analysis included 112 posts and 448 comments. The tone of comments was neutral (n=231), followed by negative (n=121) and positive (n=96). 13 users actively encouraged other users to try the procedure, while 25 advised against it. The main topics of discussions revolved around pain relief expectations and adverse events. Almost half of users commenting about pain relief expectations reported experiencing considerably lower improvement than anticipated. Pocket pain, lead fracture/migration, infection risk, and scars were common topics of discussion among users. Furthermore, users shared strategies to mitigate postoperative discomfort and offered insights into device selection based on MRI conditionality, reprogramming need, and charging prerequisites. Conclusion Our Reddit analysis identified potential targets for enhanced dialog between physicians and patients around anticipated pain relief, complications, and postoperative care. Reddit and other social media platforms may offer valuable opportunities for healthcare professionals to improve engagement with patients.

Background. Chronic kidney disease (CKD) is a well-recognized complication in patients undergoing liver transplantation (LT), particularly those with metabolic dysfunction-associated steatohepatitis (MASH), a leading cause of cirrhosis in the modern era. This study sought to refine risk stratification for CKD events post-LT in cirrhosis patients with MASH by leveraging baseline renal function at transplant. Methods. A total of 717 MASH cirrhosis patients who had LT (1997–2017) at 7 US centers (NailMASH Consortium) were analyzed. Patients were categorized by estimated glomerular filtration rate (eGFR) at transplant: low (LGFR, eGFR ≤30 mL/min/1.73 m²), medium (MGFR, eGFR >30–≤60 mL/min/1.73 m²), and high (HGFR, eGFR >60 mL/min/1.73 m²). Time-related eGFR intercepts, slopes, and assessments of advanced-stage CKD (aCKD) events, defined as 2 eGFR levels <30 mL/min/1.73 m² separated by ≥90 d, were examined. Results. Post-LT, LGFR group showed increased eGFR, whereas the HGFR group experienced a decline. The 3-mo mark was identified as a “reset point,” signifying a new reference level, beyond which a different rate of decline was observed. After 3 mo, mean eGFRs of the LGFR group approached MGFRs, whereas the mean eGFR of the HGFR group continued to decrease but remained higher than other groups during a 60-mo follow-up. LGFR patients had significantly higher aCKD probability than MGFR and HGFR groups. Subanalysis at 3 mo post-LT revealed more aCKD events in the LGFR group compared with MGFR and HGFR groups ( P < 0.0001). Conclusions. The study underscores renal impact of LT in MASH cirrhosis, indicating unique eGFR trajectories post-LT tied to baseline eGFR, with a reset point at 3 mo. Monitoring post-LT renal function, especially in those at aCKD risk, is crucial. Renal-sparing immunosuppression may help, regardless of baseline eGFR. Further studies are needed for interventions addressing renal dysfunction of patients with MASH post-LT.

PURPOSE The outcomes of anti–PD-1 agents plus fluoropyrimidine/platinum in frontline advanced gastroesophageal adenocarcinomas (aGEAs) remain poor. We investigated the safety, tolerability, and activity of fluoropyrimidine/oxaliplatin and tislelizumab with the DKK1-neutralizing antibody DKN-01 in aGEAs in a phase IIa open-label study. PATIENTS AND METHODS Patients had untreated human epidermal growth factor receptor 2–negative aGEAs, RECIST v1.1 measurable disease, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and adequate organ function. Patients received intravenous DKN-01 300 mg once every 2 weeks, tislelizumab 200 mg once every 3 weeks, oxaliplatin 130 mg/m 2 once every 3 weeks, and capecitabine 1,000 mg/m 2 twice daily on days 1-15 of each 21-day cycle. The primary end point was safety and tolerability. Key secondary end points included objective response rate (ORR) by RECISTv1.1, progression-free survival (PFS), and overall survival (OS). RESULTS Between September 18, 2020, and April 8, 2021, 25 patients were enrolled. All patients who received at least one dose of DKN-01 were included in the safety analysis. Most patients had gastroesophageal junction tumors, median age was 61 years, 76% were male, and 55% were ECOG of 0. All patients reported at least one treatment-emergent adverse event. The ORR was 73% (95% CI, 49.8 to 89.3), with a disease control rate of 95%. The ORR was 90% (95% CI, 55.5 to 99.7) in the DKK1-high tumor patients and 67% (95% CI, 29.9 to 92.5) in the DKK1-low tumor patients. The median PFS was 11.3 months (95% CI, 5.8 to 12.0) and the 12-month PFS rate was 33%. The median OS was 19.5 months (95% CI, 15.2 to 24.4) with a 12-month OS rate of 76% and an 18-month OS rate of 55%. CONCLUSION DKN-01 can be safely combined with frontline fluoropyrimidine/oxaliplatin and tislelizumab and demonstrates encouraging activity independent of PD-L1 expression levels. A randomized phase II trial is ongoing (ClinicalTrials.gov identifier: NCT04363801 ).