Marshfield Clinic Health System is an integrated health system serving Wisconsin founded in 1916. The system contains several hospitals and many clinics throughout Wisconsin, as well as a medical research institute and an education division, and employs more than 1,200 doctors and other clinicians.
Age-related proliferation of indeterminate capacity hematopoietic stem and progenitor cells bearing somatic mutations, mainly in DNMT3A, TET2, and ASXL1, is referred to as clonal hematopoiesis of indeterminate potential (CHIP). In addition to the well-known premalignant effects, CHIP causes systemic effects and predisposes to cardiovascular disease, thromboembolism, and dysfunction of multiple organs. Mutant neutrophils have been increasingly recognized as contributors to this pathology. These cells exhibit aberrant phenotypes and epigenetic alterations associated with pro-inflammatory and pro-thrombotic phenotypes that may favor NET formation. Uncontrolled NETosis may promote endothelial damage, platelet aggregation, and microvascular thrombosis that creates a vicious loop of thromboinflammation. The association of CHIP-related NETosis with venous and arterial thromboses, ischemic stroke, myocardial infarction, and organ-specific damage has been reported, although the main contribution is largely referred from indirect biomarker-based evidence or extrapolation from related conditions. Instead of detecting NET production directly, several studies employ indirect NET markers (such as MPO-DNA, citH3, and cfDNA). Activation of PAD4, generation of reactive oxygen species and inflammatory cytokines are the main modulators implicated in mechanistic studies. Clinically, therapies against NETs using DNase, PAD4, or cytokine blockade have the potential to reduce the risk of thromboinflammation. Although supported by compelling preclinical and observational evidence, there are still challenges because of the use of retrospective studies, murine models, and indirect measure of NET.The current evidence base consists primary of preclinical (murine and in vitro) studies along with observational human data. Future studies are required on prospective trials, mutation-directed biomarkers, and precision medicine modalities to regulate mutant neutrophil functions. Insight into NET-mediated pathogenesis in CHIP does not just clarify the pathways between clonal hematopoiesis and thromboinflammation and dysfunction in the body but also provides opportunities to formulate specific solutions to decrease cardiovascular and systemic illnesses in victims.
299 Background: Esophageal cancer is most often adenocarcinoma or squamous cell carcinoma, while rare histologies such as basaloid squamous carcinoma, sarcomatoid carcinoma, and neuroendocrine carcinoma (NEC) are poorly characterized. We aimed to evaluate incidence, treatment strategies, and survival outcomes of these unusual variants using a national cohort. Methods: We queried the National Cancer Database (2004–2019) for patients with esophageal cancer identified by ICD-O-3 morphology codes: basaloid squamous carcinoma (8083/3), sarcomatoid carcinoma (8033/3), and NEC (8013/3, 8246/3). Outcomes were compared with conventional squamous cell carcinoma (SCC) and adenocarcinoma (AC). Kaplan–Meier and multivariable Cox regression were used to estimate overall survival (OS). Results: Among 195,612 esophageal cancer cases, 682 (0.35%) were rare histologies: 231 basaloid SCC, 147 sarcomatoid carcinoma, and 304 NEC. Median age was 63 years, and 71% were male. Compared with SCC and AC, patients with rare histologies were more frequently diagnosed with advanced disease (56% vs 44%, p<0.01). Median OS for basaloid SCC was 15.8 months, similar to conventional SCC at 16.4 months (p=0.41). Sarcomatoid carcinoma had a median OS of 18.2 months, and outcomes improved significantly following surgical resection, with 3-year OS of 42% compared to 25% for non-surgical patients (p<0.01). NEC carried the poorest prognosis, with median OS of 10.6 months; however, patients receiving platinum-based chemotherapy demonstrated modestly improved outcomes (12.4 vs 7.8 months, p<0.01). On adjusted analysis, sarcomatoid carcinoma survival was comparable to SCC (HR 0.94, 95% CI 0.81–1.08), while NEC was independently associated with worse survival (HR 1.42, 95% CI 1.25–1.62). Conclusions: Rare histologic variants of esophageal cancer represent less than 0.5% of cases and are often diagnosed at advanced stage. Basaloid and sarcomatoid carcinomas demonstrate outcomes similar to conventional SCC when treated aggressively, while NEC carries a poor prognosis despite systemic therapy. Recognition of these subtypes is critical to guide management and inform clinical trial design for rare esophageal cancers.
BACKGROUND:Reverse shoulder arthroplasty (rTSA) and anatomic total shoulder arthroplasty (aTSA) treat glenohumeral osteoarthritis (GHOA) with comparable early outcomes. Given increasing utilization of rTSA for GHOA, we sought to evaluate outcomes of rTSA and aTSA for GHOA at early and midterm follow-up. METHODS:A retrospective propensity-matched cohort study of patients undergoing aTSA and rTSA for GHOA with early and midterm follow-up was performed. Matching included age, sex, body mass index, preoperative American Shoulder and Elbow Surgeons (ASES) score, preoperative forward elevation, and Walch glenoid morphology. Baseline patient characteristics, range of motion, ASES, Single Assessment Numeric Evaluation (SANE), visual analog scale (VAS) for pain scores, complications and revision rTSAs/aTSAs were assessed at early and midterm follow-up. RESULTS:One hundred twenty-two patients (61 per group) were included with early and midterm follow-up. Baseline characteristics, comorbidities, preoperative ASES, SANE, VAS pain scores, and range of motion were similar (P > .05). Both groups showed significant improvements in ASES, SANE, and VAS scores at both time points (P < .001); >96% achieved minimal clinically important difference for ASES. While more aTSA patients met substantial clinical benefit early (95.1% vs. 80.3%, P = .027); there was no statistically significant difference at midterm follow-up (P = .074). aTSA patients had better early internal (5.0 vs. 3.3, P < .001) and external rotation (63.0° vs. 57.0°, P = .036), with no difference at midterm follow-up. Complication rates were similar; however, aTSA had more revisions and radiolucencies. CONCLUSION:aTSA and rTSA yield similar clinical outcomes for GHOA at early and midterm follow-up. Early differences in substantial clinical benefit, internal, and external rotation with aTSA diminished by midterm follow-up. Complication rates were similar between the cohorts. One patient in the aTSA group was revised to rTSA and no patients with primary rTSA required revision. While rTSA and aTSA result in excellent clinical outcomes, longer follow-up is needed to determine durability.
Background/Objectives: Malnutrition is prevalent among patients in the pediatric intensive care unit (PICU) and has been shown to worsen in some patients during the PICU stay. In critically ill children, malnutrition is associated with longer PICU length of stay and increased mortality. Several tools have been developed and validated to screen for nutritional status in children, but none were specifically designed for critically ill children. Our study aims to fill this gap. The goal of this study was to refine and validate a novel PICU nutrition screening tool in a diverse population of critically ill children from six PICUs across the United States. Methods: Subjects underwent the nutrition screen and a Subjective Global Nutritional Assessment (SGNA). We used chi-square tests and Mann-Whitney tests to compare elements of the nutrition screen to the SGNA to identify those elements most associated with malnutrition. We used stepwise logistic regression to determine the best fitting model for a malnutrition screening tool. We proposed a scoring system using the factors identified in the best fitting model to define a positive screen. Results: We enrolled 732 subjects at six PICUs. Of these, 131 subjects (17.9%) were malnourished per the SGNA. Children with and without malnutrition did not differ with respect to age, sex, or race. The likelihood of malnutrition increased as weight-for-age percentile decreased (p < 0.001). We found that the best fitting model of a malnutrition screening tool for critically ill children included weight-for-age percentile, cancer, feeding less, parent perception of growth as poor, and being significantly underweight. We defined a positive screen that should prompt referral to a dietitian. Conclusions: We have developed a nutrition screening tool for critically ill children.
