Postexercise Ankle-Brachial Index Testing Mehta, Anurag; Sperling, Laurence S; Wells, Bryan J
JAMA : the journal of the American Medical Association,
2020-Aug-25, Letnik:
324, Številka:
8
Journal Article
•SBRT was much more common (93%) than percutaneous local tumor ablation (LTA)(7%).•Higher OS was associated with SBRT versus percutaneous LTA in early-stage NSCLC.•The OS benefit to SBRT was ...consistent across multiple patient subsets.•Patients with tumor sizes ≤2.0 cm had similar OS between treatments.
To compare patterns of care and overall survival (OS) between stereotactic body radiotherapy (SBRT) and percutaneous local tumor ablation (LTA) for non-surgically managed early-stage non-small-cell lung cancer (NSCLC).
The National Cancer Database (NCDB) was queried from 2004 to 2014 for adults with non-metastatic, node-negative invasive adenocarcinoma or squamous cell carcinoma of the lung with primary tumor size ≤5.0 cm who did not undergo surgery or chemotherapy and received SBRT or LTA. Patterns of care were assessed with multivariate logistic regression. After propensity-score weighting with generalized boosted regression, OS was assessed with univariate and doubly-robust multivariate Cox regression.
Of 15,792 patients, 14,651 (93%) received SBRT and 1141 (7%) received LTA. Increasing age (OR 1.01, p = .035), treatment at an academic institution (OR 2.94, p < .001), increasing tumor size (OR 1.05, p < .001), and more recent year of diagnosis (OR 1.43, p < .001) were predictive of treatment with SBRT, whereas comorbidities (OR 0.74, p = .003) and treatment at a high-volume facility (OR 0.05, p < .001) were predictive for LTA. At a median follow-up of 26.2 months, SBRT was associated with improved OS relative to LTA within a propensity-score weighted doubly-robust multivariate analysis (HR 0.71, p < .001). On weighted subgroup analyses, improved OS was observed with SBRT for tumor sizes >2.0 cm (HR 0.72, p < .001) and for those treated at high-volume facilities (HR 0.71, p < .001). No OS difference was found with SBRT or LTA in tumor sizes ≤2.0 cm (HR 0.90, p = .227).
Within the NCDB, SBRT was more commonly utilized and was associated with improved OS when compared to percutaneous LTA for patients with non-surgically managed early-stage NSCLC. Patients with small tumor volumes likely represent an appropriate population for future prospective randomized comparisons between SBRT and LTA.
We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients.
Sacituzumab govitecan was studied in patients with pretreated (median, 2; range, ...1-7) mSCLC who received either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles. The primary endpoints were safety and objective response rate (ORR); duration of response, progression-free survival (PFS), and overall survival (OS) were secondary endpoints.
Sixty percent of patients showed tumor shrinkage from baseline CTs. On an intention-to-treat basis (
= 50), the ORR was 14% (17% for the 10-mg/kg group); the median response duration, 5.7 months; the clinical benefit rate (CBR ≥4 months), 34%; median PFS, 3.7 months; and median OS, 7.5 months. There was a suggested improvement in PR, CBR, and PFS with sacituzumab govitecan in second-line patients who were sensitive to first-line therapy, but no difference between first-line chemosensitive versus chemoresistant patients in the overall population. There was a statistically significant higher OS in those patients who received prior topotecan versus no topotecan therapy in a small subgroup. Grade ≥3 adverse events included neutropenia (34%), fatigue (13%), diarrhea (9%), and anemia (6%). Trop-2 tumor staining was not required for patient selection. No antibodies to the drug conjugate or its components were detected on serial blood collections.
Sacituzumab govitecan appears to have a safe and effective therapeutic profile in heavily pretreated mSCLC patients, including those who are chemosensitive or chemoresistant to first-line chemotherapy. Additional studies as a monotherapy or combination therapy are warranted.
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Myocardial infarction secondary to spontaneous coronary artery dissection (SCAD) can be traumatic and potentially trigger posttraumatic stress disorder (PTSD). In a large, multicenter, registry-based ...cohort, we documented prevalence of lifetime and past-month SCAD-induced PTSD, as well as related treatment seeking, and examined a range of health-relevant correlates of SCAD-induced PTSD.
Patients with SCAD were enrolled in the iSCAD (International SCAD) Registry. At baseline, site investigators completed medical report forms, and patients reported demographics, medical/SCAD history, psychosocial factors (including SCAD-induced PTSD symptoms), health behaviors, and health status via online questionnaires. Of 1156 registry patients, 859 patients (93.9% women; mean age, 52.3 years) completed questionnaires querying SCAD-induced PTSD. Nearly 35% (n=298) of patients met diagnostic criteria for probable SCAD-induced PTSD in their lifetime, and 6.4% (n=55) met criteria for probable past-month PTSD. Of 811 patients ever reporting any SCAD-induced PTSD symptoms, 34.8% indicated seeking treatment for this distress. However, 46.0% of the 298 patients with lifetime probable SCAD-induced PTSD diagnoses reported never receiving trauma-related treatment. Younger age at first SCAD, fewer years since SCAD, being single, unemployed status, more lifetime trauma, and history of anxiety were associated with greater past-month PTSD symptom severity in multivariable regression models. Greater past-month SCAD-induced PTSD symptoms were associated with greater past-week sleep disturbance and worse past-month disease-specific health status when adjusting for various risk factors.
Given the high prevalence of SCAD-induced PTSD symptoms, efforts to support screening for these symptoms and connecting patients experiencing distress with empirically supported treatments are critical next steps.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT04496687.
Lymphopenia is common in severe coronavirus disease (COVID-19), yet the immune mechanisms are poorly understood. As inflammatory cytokines are increased in severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2) infection, we hypothesized a role in contributing to reduced T-cell numbers.
We sought to characterize the functional SARS-CoV-2 T-cell responses in patients with severe versus recovered, mild COVID-19 to determine whether differences were detectable.
Using flow cytometry and single-cell RNA sequence analyses, we assessed SARS-CoV-2-specific responses in our cohort.
In 148 patients with severe COVID-19, we found lymphopenia was associated with worse survival. CD4
lymphopenia predominated, with lower CD4
/CD8
ratios in severe COVID-19 compared with patients with mild disease (
< 0.0001). In severe disease, immunodominant CD4
T-cell responses to Spike-1 (S1) produced increased
TNF-α (tumor necrosis factor-α) but demonstrated impaired S1-specific proliferation and increased susceptibility to activation-induced cell death after antigen exposure. CD4
TNF-α
T-cell responses inversely correlated with absolute CD4
counts from patients with severe COVID-19 (
= 76;
= -0.797;
< 0.0001).
TNF-α blockade, including infliximab or anti-TNF receptor 1 antibodies, strikingly rescued S1-specific CD4
T-cell proliferation and abrogated S1-specific activation-induced cell death in peripheral blood mononuclear cells from patients with severe COVID-19 (
< 0.001). Single-cell RNA sequencing demonstrated marked downregulation of type-1 cytokines and NFκB signaling in S1-stimulated CD4
cells with infliximab treatment. We also evaluated BAL and lung explant CD4
T cells recovered from patients with severe COVID-19 and observed that lung T cells produced higher TNF-α compared with peripheral blood mononuclear cells.
Together, our findings show CD4
dysfunction in severe COVID-19 is TNF-α/TNF receptor 1-dependent through immune mechanisms that may contribute to lymphopenia. TNF-α blockade may be beneficial in severe COVID-19.
Background Fibromuscular dysplasia (FMD) is a disease of unknown etiology that causes stenosis, aneurysmal dilatation, and dissection of vascular beds. Known to affect medium-sized arteries, FMD is ...not typically considered to affect the aorta. We tested the hypothesis that aortic size in FMD is abnormal compared with age- and sex-matched controls. Methods and Results Medical records and computed tomography angiography images were reviewed in female patients with a diagnosis of FMD who were seen in the vascular medicine clinic at Emory Healthcare. Aortic dimensions were measured at 6 different landmarks. Using 2 sample
tests, the aortic measurements and height-indexed measurements were compared with published normal values in healthy women of a similar age. A total of 94 female patients were included in the study. The median age was 57 (interquartile range, 50-65). FMD involvement was present most commonly in the extracranial carotid (77.7%) and renal (43.6%) arteries. All 6 aortic segments were found to be larger in both absolute measures and height-indexed measures in the FMD population (
<0.001). The largest differences were observed within the absolute measures of the sinotubular junction with mean±SD (mm) (29.9±4.1) versus (27±2.5), ascending aorta (32.7±4.4) versus (30.0±3.5), and descending aorta (24.7±3.0) versus (22.0±2.0) (
<0.001). Conclusions Aortic diameters in female patients with FMD are larger when compared with published age- and sex-matched normal values. These findings suggest that FMD may also affect the large-sized arteries.
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