Citations

AbstractA new generation of disease‐specific molecular imaging agents is poised to revolutionize fluorescence‐guided surgery. Pafolacianine has been approved for adult lung and ovarian cancers. We demonstrate a proof of concept for pediatric surgeons treating young adults with pulmonary metastatic sarcomas. Five successful fluorescence‐guided pulmonary metastasectomy operations were performed in young adult patients with metastatic osteosarcoma or Ewing sarcoma following administration of pafolacianine. All osteosarcoma lesions identified using standard techniques were also markedly fluorescent in patients. Novel fluorescent molecular agents targeted to tumor‐specific receptors have promise of increased sensitivity and specificity for detecting metastatic nodules and enhancing surgical clearance of disease.

Background Adults with congenital heart disease (CHD) are at increased risk of stroke but high‐quality population level data on stroke incidence in these patients are scant. Methods and Results A retrospective whole‐population Western Australian cohort of adult patients with CHD aged 18 to 64 years was created and followed from January 2000 to December 2017 using linked hospital data. Stroke incidence rates within the adult cohort with CHD were calculated and compared with the general population via direct standardization. A nested case–control design assessed predictors of ischemic and hemorrhagic stroke within the cohort. Among 7916 adults with CHD, 249 (3.1%) incident strokes occurred at a median age of 47 years; 186 (2.3%) ischemic, 33 (0.4%) hemorrhagic and 30 (0.4%) unspecified strokes. Ischemic and hemorrhagic stroke incidence was, respectively, 9 and 3 times higher in adults with CHD than the general population. Absolute risk was low with annual rates of 0.26% (ischemic) and 0.05% (hemorrhagic). Highest rates were observed in adults with shunt and left‐sided lesions. Predictors of ischemic stroke in adults with CHD included recent cardiac surgery, left‐sided valve repair/replacements, shunt lesions, and traditional risk factors (hypertension, infective endocarditis, peripheral vascular disease, and tobacco use). Mental health disorders and increasing Charlson's comorbidity scores were strongly associated with higher risk of ischemic and hemorrhagic stroke. The CHA 2 DS 2 VASc score was associated with ischemic stroke incidence. Conclusions This study provides the first population‐based stroke incidence estimates for adults with CHD in Australia, showing elevated stroke risk across different CHD lesions. It highlights the potential clinical importance of managing comorbidities, especially mental health.

INTRODUCTION: Prophylactic pancreatic stent placement (PSP) is effective for preventing pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) in high-risk cases, but the optimal technical approach to this intervention remains uncertain. METHODS: In this secondary analysis of 787 clinical trial patients who underwent successful stent placement, we studied the impact of (i) whether pancreatic wire access was achieved for the sole purpose of PSP or naturally during the conduct of the case, (ii) the amount of effort expended on PSP, (iii) stent length, (iv) stent diameter, and (v) guidewire caliber. We used logistic regression models to examine the adjusted association between each technical factor and post-ERCP pancreatitis (PEP). RESULTS: Ninety-one of the 787 patients experienced PEP. There was no clear association between PEP and whether pancreatic wire access was achieved for the sole purpose of PSP (vs occurring naturally; odds ratio [OR] 0.82, 95% confidence interval [CI] 0.37–1.84), whether substantial effort expended on stent placement (vs nonsubstantial effort; OR 1.58, 95% CI 0.73–3.45), stent length (>5 vs ≤5 cm; OR 1.01, 95% CI 0.63–1.61), stent diameter (≥5 vs <5 Fr; OR 1.13, 95% CI 0.65–1.96), or guidewire caliber (0.035 vs 0.025 in; 0.83, 95% CI 0.49–1.41). DISCUSSION: The 5 modifiable technical factors studied in this secondary analysis of large-scale randomized trial data did not appear to have a strong impact on the benefit of prophylactic PSP in preventing PEP after high-risk ERCP. Within the limitations of post hoc subgroup analysis, these findings may have important implications in procedural decision making and suggest that the benefit of PSP is robust to variations in technical approach.

Abstract Aims : Direct oral anticoagulants (DOACs) are widely used for stroke prevention in people with non-valvular atrial fibrillation/flutter (NVAF). Anticoagulants have different bleeding profiles. Apixaban is associated with the lowest bleeding risk. This study evaluates the interaction between DOAC used and right ventricular systolic pressure (RVSP) on echocardiogram and bleeding rates. It was hypothesized that pulmonary hypertension may be associated with excess bleeding based on anticoagulant-specific pharmacologic profiles. Methods & Results : A retrospective analysis of a database was conducted. Multivariable regression models for bleeding rates were developed using a causative analysis approach among participants who had undergone an echocardiogram, and interaction terms for DOAC choice were incorporated. Stratum specific estimates were calculated using linear computation. Patients taking Apixaban had lower bleeding rates than those taking Rivaroxaban and Dabigatran. Among those without pulmonary hypertension, there was no difference in bleeding rates. Where RVSP was ≥45mmHg, there was a 90% increase in bleeding rates with use of Dabigatran (HR 1.99, p=0.024) and Rivaroxaban (HR 1.86, p=0.042) compared to Apixaban (Figure 1). Conclusions : Elevated RVSP is associated with excess bleeding in patients taking Rivaroxaban and Dabigatran, but not Apixaban, after controlling for confounding variables.

INTRODUCTION: Reflux bile acids are believed to promote esophageal adenocarcinoma (EAC), but the role of systemic bile acids is unknown. This study aimed to assess associations between systemic bile acids and stages of Barrett's esophagus (BE) progression. METHODS: Subjects with and without BE were enrolled in this multicenter cross-sectional study. Targeted serum bile acid profiling was performed, and a subset of subjects completed a validated food frequency questionnaire. RNA sequencing was performed on BE or gastric cardia tissue to assess bile acid associations with gene expression. RESULTS: A total of 141 subjects were enrolled with serum bile acids profiled (49 non-BE; 92 BE: 44 no dysplasia, 25 indefinite/low grade dysplasia, 23 high-grade dysplasia/EAC). Lower Healthy Eating Index score, older age, higher body mass index, and no proton pump inhibitor use were associated with increased levels of multiple bile acids. Global bile acid pools were distinct between non-BE and stages of BE neoplasia ( P = 0.004). Increasing cholic acid was associated with high-grade dysplasia/EAC compared with non-BE, even after adjusting for EAC risk factors (adjusted odds ratio 2.03, 95% confidence interval 1.11–3.71) as was the combination of unconjugated primary bile acids (adjusted odds ratio 1.81, 95% confidence interval 1.04–3.13). High cholic acid levels were associated with tissue gene expression changes including increased DNA replication and reduced lymphocyte differentiation genes. DISCUSSION: Alterations in serum bile acids are independently associated with advanced neoplasia in BE and may contribute to neoplastic progression. Future studies should explore associated gut microbiome changes, proneoplastic effects of bile acids, and whether these bile acids, particularly cholic acid, represent potential biomarkers or viable therapeutic targets for advanced neoplasia in BE.

OBJECTIVE Posterior lumbar interbody fusion (PLIF) and/or transforaminal lumbar interbody fusion (TLIF), referred to as "PLIF/TLIF," is a commonly performed operation for lumbar spondylolisthesis. Its long-term cost-effectiveness has not been well described. The aim of this study was to determine the 5-year cost-effectiveness of PLIF/TLIF for grade 1 degenerative lumbar spondylolisthesis using prospective data collected from the multicenter Quality Outcomes Database (QOD). METHODS Patients enrolled in the prospective, multicenter QOD grade 1 lumbar spondylolisthesis module were included if they underwent single-stage PLIF/TLIF. EQ-5D scores at baseline, 3 months, 12 months, 24 months, 36 months, and 60 months were used to calculate gains in quality-adjusted life years (QALYs) associated with surgery relative to preoperative baseline. Healthcare-related costs associated with the index surgery and related reoperations were calculated using Medicare reimbursement–based cost estimates and validated using price transparency diagnosis-related group (DRG) charges and Medicare charge-to-cost ratios (CCRs). Cost per QALY gained over 60 months postoperatively was assessed. RESULTS Across 12 surgical centers, 385 patients were identified. The mean patient age was 60.2 (95% CI 59.1–61.3) years, and 38% of patients were male. The reoperation rate was 5.7%. DRG 460 cost estimates were stable between our Medicare reimbursement–based models and the CCR-based model, validating the focus on Medicare reimbursement. Across the entire cohort, the mean QALY gain at 60 months postoperatively was 1.07 (95% CI 0.97–1.18), and the mean cost of PLIF/TLIF was $31,634. PLIF/TLIF was associated with a mean 60-month cost per QALY gained of $29,511. Among patients who did not undergo reoperation (n = 363), the mean 60-month QALY gain was 1.10 (95% CI 0.99–1.20), and cost per QALY gained was $27,591. Among those who underwent reoperation (n = 22), the mean 60-month QALY gain was 0.68 (95% CI 0.21–1.15), and the cost per QALY gained was $80,580. CONCLUSIONS PLIF/TLIF for degenerative grade 1 lumbar spondylolisthesis was associated with a mean 60-month cost per QALY gained of $29,511 with Medicare fees. This is far below the well-established societal willingness-to-pay threshold of $100,000, suggesting long-term cost-effectiveness. PLIF/TLIF remains cost-effective for patients who undergo reoperation.