Importance Long-term outcomes of radiotherapy are important in understanding the risks and benefits of therapies for patients with brain metastases. Objective To determine how the use of postoperative whole-brain radiotherapy (WBRT) or stereotactic radiosurgery (SRS) is associated with quality of life (QOL), cognitive function, and intracranial tumor control in long-term survivors with 1 to 4 brain metastases. Design, Setting, and Participants This secondary analysis of a randomized phase 3 clinical trial included 48 institutions in the US and Canada. Adult patients with 1 resected brain metastases but limited to those with 1 to 4 brain metastasis were eligible. Unresected metastases were treated with SRS. Long-term survivors were defined as evaluable patients who lived longer than 1 year from randomization. Patients were recruited between July 2011 and December 2015, and data were first analyzed in February 2017. For the present study, intracranial tumor control, cognitive deterioration, QOL, and cognitive outcomes were measured in evaluable patients who were alive at 12 months from randomization and reanalyzed in June 2017. Interventions Stereotactic radiosurgery or WBRT. Main Outcomes and Measures Intracranial tumor control, toxic effects, cognitive deterioration, and QOL. Results Fifty-four patients (27 SRS arm, 27 WBRT arm; female to male ratio, 65% vs 35%) were included for analysis with a median follow-up of 23.8 months. Cognitive deterioration was less frequent with SRS (37%-60%) compared with WBRT (75%-91%) at all time points. More patients declined by 2 or more standard deviations (SDs) in 1 or more cognitive tests for WBRT compared with SRS at 3, 6, and 9 months (70% vs 22%, 46% vs 19%, and 50% vs 20%, respectively). A 2 SD decline in at least 2 cognitive tests was associated with worse 12-month QOL in emotional well-being, functional well-being, general, additional concerns, and total scores. Overall QOL and functional independence favored SRS alone for categorical change at all time points. Total intracranial control for SRS alone vs WBRT at 12 months was 40.7% vs 81.5% (difference, −40.7; 95% CI, −68.1% to −13.4%), respectively. Data were first analyzed in February 2017. Conclusions and Relevance The use of SRS alone compared with WBRT resulted in less cognitive deterioration among long-term survivors. The association of late cognitive deterioration with WBRT was clinically meaningful. A significant decline in cognition (2 SD) was associated with overall QOL. However, intracranial tumor control was improved with WBRT. This study provides detailed insight into cognitive function over time in this patient population. Trial Registration ClinicalTrials.gov Identifier: NCT01372774 ; ALLIANCE/CCTG: N107C/CEC.3 (Alliance for Clinical Trials in Oncology/Canadian Cancer Trials Group)
Quantifying misdiagnosis rates from cross‐calibration biases and precision errors in dual‐energy X‐ray absorptiometry of the femoral neck
Abstract Background Dual‐energy X‐ray absorptiometry (DXA) is an exam that measures areal bone mineral density (aBMD) and is regularly used to diagnose and monitor osteoporosis. Except for exam quality issues such as operator error, the quantitative results of an exam are not modified by a radiologist or other physician. DXA cross‐calibration errors can shift diagnoses, conceivably leading to alternate intervention decisions and patient outcomes. Purpose After identifying and correcting a cross‐calibration bias of 3.8% in our two DXA scanners’ aBMD measurements, we investigated misdiagnosis rates for given cross‐calibration errors in a single patient cohort to determine the impact on patient care and the value of cross‐calibration quality control. Methods The studied cohort was 8012 patients of all ages and sexes with femoral neck exams that were scanned on a single DXA unit from October 1, 2018 to March 31, 2021. There were six subcohorts delineated by age and sex, three female groups and three male groups. Data reporting focused on the highest risk subcohort of 2840 females aged 65 or older. The DXA unit had no calibration changes during that time. Only one femoral neck—left or right—was randomly chosen for analysis. Patients with multiple qualifying exams within the time interval had one exam randomly chosen. The proof‐of‐principle simulation shifted the aBMD values within a range of ±10%, ±8%, ±6%, ±4%, ±3.5%, ±3%, ±2.5%, ±2%, ±1.5%, ±1%, ±0.5%, and 0 (no shift); the cross‐calibration shifts were informed by published results and institutional experience. Measurement precision was modeled by randomly sampling a Gaussian distribution characterized by the worst acceptable least significant change (LSC) of 6.9%, with 100 000 samplings for each patient. T‐scores were recalculated from the shifted aBMD values, followed by reassigned diagnoses from the World Health Organization's T‐score‐based scheme. Results The unshifted original subcohort of women aged 65 and older had 599 normal diagnoses (21.1% of the cohort), 1784 osteopenia diagnoses (62.8%), and 455 osteoporosis diagnoses (16.1%). Osteoporosis diagnosis rates were highly sensitive to aBMD shifts. At the extrema, a −10% aBMD shift led to +161% osteoporosis cases, and a +10% aBMD shift led to −64.5% osteoporosis cases. Within the more plausible ±4% aBMD error range, the osteoporosis diagnosis rate changed −10.5% per +1% aBMD shift as indicated by linear regression ( R 2 = 0.98). Except for the men aged 49 years and younger subcohort, the total cohort and five subcohorts had fit line slopes ranging between −9.7% and −12.1% with R 2 ≥ 0.98. Cross‐calibration bias had greater influence for diagnosis count rates compared to measurement precision, that is, LSC. Conclusions These results quantify the degree of misdiagnosis that can occur in a clinically relevant cohort due to cross‐calibration bias. In medical practices where patients may be scanned on more than one DXA unit, ensuring cross‐calibration quality is a critical and high‐value quality control task with direct impact on patient diagnosis and treatment course. The clinical impact and incidence of poor DXA quality control practices, and cross‐calibration in particular, should be studied further.
Purified Exosome Product Enhances Chondrocyte Survival and Regeneration by Modulating Inflammation and Promoting Chondrogenesis
Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature | October 10, 2022 | Volume: No volume available | Issue: No issue available | Pages: No page available
AbstractSonography and specific shoulder positions allow for injections into both the long head of the biceps tendon sheath (LHBTS) and the subacromial space (SS) with one needlestick. We validated this technique using cadavers. An experienced proceduralist injected latex solution into 12 unembalmed cadaveric shoulders, aiming for the LHBTS and SS, using an ultrasound‐guided injection technique that employs a single‐needle entry point. An experienced surgeon dissected each specimen and graded latex location as: (1) completely accurate (in both the SS and LHBTS); (2) partially accurate (in either the SS or LHBTS); (3) accurate with overflow (in both locations, but also elsewhere); (4) partially accurate with overflow (in either location, but also somewhere else); or (5) completely inaccurate (no latex in either location). All 12 ultrasound‐guided injections using the technique accurately placed latex into both LHBTS and SS (100% accuracy). Latex was also found in adjacent regions after two (17%) injections: one within the shoulder joint and one within the deltoid musculature. This newly described technique allows highly accurate access to the LHBTS and SS with single‐needle entry. This technique could become a favored alternative to subjecting patients to two needlesticks and preparing separate injections to address often concomitant pathologies.
T100: Long term Follow-up of a Phase I Study Combinations of Ipilimumab, Nivolumab and Brentuximab Vedotin in Patients with Relapsed/Refractory Hodgkin Lymphoma: A trial of the ECOG-ACRIN Research Group (E4412: Arms A-I)
Abstract Background The association of renin with adverse kidney outcomes is largely unknown, and renin measurement strategies vary. We aimed to measure the clinical correlates of different renin measurements and the association between renin and incident chronic kidney disease (CKD), end-stage kidney disease (ESKD), and mortality. Methods We performed a prospective cohort analysis of 9,420 participants in the Atherosclerosis Risk in Communities study followed from 1996 to 1998 through 2019. We estimated longitudinal associations of renin measured using SomaScan modified nucleotide aptamer assay with incident CKD, ESKD, and death using Cox proportional hazards models. Using samples from a subsequent study visit, we compared SomaScan renin with plasma renin activity (PRA) and renin level from Olink, and estimated associations with covariates using univariate and multivariable regression. Results Higher SomaScan renin levels were associated with a higher risk of incident CKD (hazard ratio per two-fold higher [HR], 1.14; 95% confidence interval [CI], 1.09 to 1.20), ESKD (HR, 1.20; 95% CI, 1.03 to 1.41), and mortality (HR, 1.08; 95% CI, 1.04 to 1.13) in analyses adjusted for demographic, clinical, and socioeconomic covariates. SomaScan renin was moderately correlated with PRA (r = 0.61) and highly correlated with Olink renin (r = 0.94). SomaScan renin and PRA had similar clinical correlates except for divergent associations with age and beta-blocker use, both of which correlated positively with SomaScan renin but negatively with PRA. Conclusions SomaScan aptamer-based renin level was associated with a higher risk of CKD, ESKD, and mortality. It was moderately correlated with PRA, sharing generally similar clinical covariate associations.