Tertiary lymphoid tissues (TLTs) have been observed in the meninges of multiple sclerosis (MS) patients, but the stromal cells and molecular signals that support TLTs remain unclear. Here, we show that T helper 17 (Th17) cells induced robust TLTs within the brain meninges that were associated with local demyelination during experimental autoimmune encephalitis (EAE). Th17-cell-induced TLTs were underpinned by a network of stromal cells producing extracellular matrix proteins and chemokines, enabling leukocytes to reside within, rather than simply transit through, the meninges. Within the CNS, interactions between lymphotoxin αβ (LTαβ) on Th17 cells and LTβR on meningeal radio-resistant cells were necessary for the propagation of de novo interleukin-17 responses, and activated T cells from MS patients expressed elevated levels of LTβR ligands. Therefore, input from both Th17 cells and the lymphotoxin pathway induce the formation of an immune-competent stromal cell niche in the meninges.
IMPORTANCEThe association between delayed surgical treatment and oncologic outcomes in patients with non-small cell lung cancer (NSCLC) is poorly understood given that prior studies have used imprecise definitions for the date of cancer diagnosis. OBJECTIVE To use a uniform method to quantify surgical treatment delay and to examine its association with several oncologic outcomes.
DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study was conducted using a novel data set from the Veterans Health Administration (VHA) system. Included patients had clinical stage I NSCLC and were undergoing resection from 2006 to 2016 within the VHA system. Time to surgical treatment (TTS) was defined as the time between preoperative diagnostic computed tomography imaging and surgical treatment. We evaluated the association between TTS and several delay-associated outcomes using restricted cubic spline functions. Data analyses were performed in November 2021.
EXPOSURE Wait time between cancer diagnosis and surgical treatment (ie, TTS).
MAIN OUTCOMES AND MEASURESSeveral delay-associated oncologic outcomes, including pathologic upstaging, resection with positive margins, and recurrence, were assessed. We also assessed overall survival. RESULTS Among 9904 patients who underwent surgical treatment for clinical stage I NSCLC, 9539 (96.3%) were men, 4972 individuals (50.5%) were currently smoking, and the mean (SD) age was 67.7 (7.9) years. The mean (SD) TTS was 70.1 (38.6) days. TTS was not associated with increased risk of pathologic upstaging or positive margins. Recurrence was detected in 4158 patients (42.0%) with median (interquartile range) follow-up of 6.15 (2.51-11.51) years. Factors associated with increased risk of recurrence included younger age (hazard ratio [HR] for every 1-year increase in age, 0.992; 95% CI, 0.987-0.997; P = .003), higher Charlson Comorbidity Index score (HR for every 1-unit increase in
Background: Cancer cells evade death caused by extracellular matrix (ECM)-detachment to facilitate metastasis. Results: ErbB2-expressing cancer cells form aggregates during ECM-detachment that promote survival signaling through EGFR. Conclusion: Multicellular aggregation in ErbB2 positive cancer cells promotes survival by preventing EGFR degradation. Significance: Disrupting aggregation or inhibiting EGFR may be effective strategies to eliminate ErbB2-expressing cancer cells during ECM-detachment.
Objective:
The aim of this study was to compare quality of care and outcomes between Veteran and non-Veteran patients undergoing surgery for clinical stage I non-small cell lung cancer (NSCLC).
Background:
Prior studies and the lay media have questioned the quality of care that Veterans with lung cancer receive through the VHA. We hypothesized Veterans undergoing surgery for early-stage NSCLC receive high quality care and have similar outcomes compared to the general population.
Methods:
We performed a retrospective cohort study of patients with clinical stage I NSCLC undergoing resection from 2006 to 2016 using a VHA dataset. Propensity score matching for baseline patient- and tumor-related variables was used to compare operative characteristics and outcomes between the VHA and the National Cancer Database (NCDB).
Results:
The unmatched cohorts included 9981 VHA and 176,304 NCDB patients. The VHA had more male, non-White patients with lower education levels, higher incomes, and higher Charlson/Deyo scores. VHA patients had inferior unadjusted 30-day mortality (VHA 2.1% vs NCDB 1.7%, P = 0.011) and median overall survival (69.0 vs 88.7 months, P < 0.001). In the propensity matched cohort of 6792 pairs, VHA patients were more likely to have minimally invasive operations (60.0% vs 39.6%, P < 0.001) and only slightly less likely to receive lobectomies (70.1% vs 70.7%, P = 0.023). VHA patients had longer lengths of stay (8.1 vs 7.1 days, P < 0.001) but similar readmission rates (7.7% vs 7.0%, P = 0.132). VHA patients had significantly better 30-day mortality (1.9% vs 2.8%, P < 0.001) and median overall survival (71.4 vs 65.2 months, P < 0.001).
Conclusions:
Despite having more comorbidities, Veterans receive exceptional care through the VHA with favorable outcomes, including significantly longer overall survival, compared to the general population.
Patients with anastomotic leaks had increased variance in their preoperative oral and gastric flora. Microbiome analysis could help identify patients at higher risk for leak after esophagectomy.
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