Primary mediastinal B cell lymphoma (PMBCL) is an uncommon lymphoma for which trials are few with small patient numbers. The role of radiation therapy (RT) after standard immunochemotherapy for ...early-stage disease has never been studied prospectively. We used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate PMBCL and the impact of RT on outcomes.
We queried the SEER database for patients with stage I-II PMBCL diagnosed from 2001 to 2011. Retrievable data included age, gender, race (white/nonwhite), stage, extranodal disease, year of diagnosis, and use of RT as a component of definitive therapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA) log-rank and multivariate (MVA) Cox proportional hazards regression analyses were performed.
Two hundred fifty patients with stage I-II disease were identified, with a median follow-up time of 39 months (range, 3-125 months). The median age was 36 years (range, 18-89 years); 61% were female; 76% were white; 45% had stage I disease, 60% had extranodal disease, and 55% were given RT. The 5-year OS for the entire cohort was 86%. On UVA, OS was improved with RT (hazard ratio HR 0.446, P=.029) and decreased in association with nonwhite race (HR 2.70, P=.006). The 5-year OS was 79% (no RT) and 90% (RT). On MVA, white race and RT remained significantly associated with improved OS (P=.007 and .018, respectively). The use of RT decreased over time: 61% for the 67 patients whose disease was diagnosed from 2001 to 2005 and 53% in the 138 patients treated from 2006 to 2010.
This retrospective population-based analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT. Nearly half of patients treated in the United States do not receive RT, and its use appears to be declining. In the absence of phase 3 data, the use of RT should be strongly considered for its survival benefit in early-stage disease.
Purpose We evaluated survival outcomes between dose-escalated EBRT (external beam radiotherapy) vs EBRT plus brachytherapy for intermediate and high risk prostate cancer using NCDB (National Cancer ...Data Base). Materials and Methods Patients with cN0M0 prostate cancer treated from 2004 to 2006 were divided into radiotherapy comparison groups, including EBRT alone (75.6 to 81 Gy) and EBRT (40 to 50.4 Gy) plus brachytherapy with EBRT delivered at 1.8 to 2.0 Gy per fraction. Brachytherapy data were limited to yes/no with no information on modality, dose or schedule. Eligible patients were known to have received androgen deprivation therapy. Overall survival was evaluated using multivariate Cox regression and propensity score matched analyses. Results Of the 20,279 study patients with prostate cancer, including 12,617 at intermediate risk and 7,662 at high risk, 71.3% received EBRT alone and 28.7% received EBRT plus brachytherapy. Median followup was 82 months (range 3 to 120) and median age was 70 years (range 36 to 90). On multivariate analysis compared to EBRT alone (75.6 to 81 Gy) EBRT plus brachytherapy was associated with improved survival (HR 0.75, p < 0.001). This significance remained consistent for intermediate and high risk when analyzed separately (HR 0.73 and 0.76, respectively, each p < 0.001). However on subset analysis compared to very high dose EBRT alone (79.2 to 81 Gy) in all patients combined EBRT plus brachytherapy was not associated with improved survival (HR 0.91, p = 0.083). Conclusion Compared to EBRT (75.6 to 81 Gy) we observed an association of EBRT plus brachytherapy with a decreased risk of death in men with intermediate and high risk prostate cancer. However this association was no longer significant when EBRT doses of 79.2 to 81 Gy were used.
Acute respiratory distress syndrome (ARDS) is associated with long-term impairments in brain and muscle function that significantly impact the quality of life of those who survive the acute illness. ...The mechanisms underlying these impairments are not yet well understood, and evidence-based interventions to minimize the burden on patients remain unproved. The NHLBI of the NIH assembled a workshop in April 2023 to review the state of the science regarding ARDS-associated brain and muscle dysfunction, to identify gaps in current knowledge, and to determine priorities for future investigation. The workshop included presentations by scientific leaders across the translational science spectrum and was open to the public as well as the scientific community. This report describes the themes discussed at the workshop as well as recommendations to advance the field toward the goal of improving the health and well-being of ARDS survivors.
Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition.
Does a single high-dose (540,000 International Units) enteral ...treatment of vitamin D3 given shortly after hospital admission in critically ill patients who are vitamin D deficient improve long-term global cognition or executive function?
This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment vs placebo in critically ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median of 443 days (interquartile range, 390-482 days) after randomization and were compared using multivariate proportional odds regression. Adjusted ORs of > 1.0 would indicate better outcomes in the vitamin D3 group compared with the placebo group.
Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 treatment and 48 patients randomized to placebo. The adjusted median RBANS score at follow-up was 79.6 (95% CI, 73.0-84.0) in the vitamin D3 group and 82.1 (95% CI, 74.7-84.6) in the placebo group (adjusted OR, 0.83; 95% CI, 0.50-1.38). The adjusted median executive function composite scores were 8.1 (95% CI, 6.8-9.0) and 8.7 (95% CI, 7.4-9.3), respectively (adjusted OR, 0.72; 95% CI, 0.36-1.42).
In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function.
ClinicalTrials.gov; No.: NCT03733418; URL: www.clinicaltrials.gov
Seagrasses are important marine ecosystems situated throughout the world’s coastlines. They are facing declines around the world due to global and local threats such as rising ocean temperatures, ...coastal development and pollution from sewage outfalls and agriculture. Efforts have been made to reduce seagrass loss through reducing local and regional stressors, and through active restoration. Seagrass restoration is rapidly maturing but improved restoration practices are needed to enhance the success of future programs. Major gaps in knowledge remain, especially our understanding of how to restore tropical species in Australia. Prior research efforts have provided valuable insights into factors influencing the outcomes of restoration and there are now several examples of successful large-scale restoration programs. A variety of tools and techniques have recently been developed that will improve the efficiency, cost effectiveness, and scalability of restoration programs. This review describes emerging techniques for restoration, key considerations for future programs, and highlights the benefits of increased collaboration, Traditional Owner (First Nation) and stakeholder engagement. Combined, these lessons and emerging approaches show that seagrass restoration is possible and efforts should be directed at upscaling seagrass restoration into the future. This is critical for the future conservation of this important ecosystem and the ecological and coastal communities they support.
Structural chromosomal changes including copy number aberrations (CNAs) are a major feature of multiple myeloma (MM), however their evolution in context of modern biological therapy is not well ...characterized. To investigate acquisition of CNAs and their prognostic relevance in context of first-line therapy, we profiled tumor diagnosis-relapse pairs from 178 NCRI Myeloma XI (ISRCTN49407852) trial patients using digital multiplex ligation-dependent probe amplification. CNA profiles acquired at relapse differed substantially between MM subtypes: hyperdiploid (HRD) tumors evolved predominantly in branching pattern vs. linear pattern in t(4;14) vs. stable pattern in t(11;14). CNA acquisition also differed between subtypes based on CCND expression, with a marked enrichment of acquired del(17p) in CCND2 over CCND1 tumors. Acquired CNAs were not influenced by high-dose melphalan or lenalidomide maintenance randomization. A branching evolution pattern was significantly associated with inferior overall survival (OS; hazard ratio (HR) 2.61, P = 0.0048). As an individual lesion, acquisition of gain(1q) at relapse was associated with shorter OS, independent of other risk markers or time of relapse (HR = 2.00; P = 0.021). There is an increasing need for rational therapy sequencing in MM. Our data supports the value of repeat molecular profiling to characterize disease evolution and inform management of MM relapse.
Purpose. Super-selective intra-ophthalmic artery chemotherapy (SSIOAC) is an eye-targeted drug-delivery strategy to treat retinoblastoma, the most prevalent primary ocular malignancy in children. ...Unfortunately, recent clinical reports associate adverse vascular toxicities with SSIOAC using melphalan, the most commonly used chemotherapeutic. Methods. To explore reasons for the unexpected vascular toxicities, we examined the effects of melphalan, as well as carboplatin (another chemotherapeutic used with retinoblastoma), in vitro using primary human retinal endothelial cells, and in vivo using a non-human primate model, which allowed us to monitor the retina in real time during SSIOAC. Results. Both melphalan and carboplatin triggered human retinal endothelial cell migration, proliferation, apoptosis, and increased expression of adhesion proteins intracellullar adhesion molecule-1 ICAM-1 and soluble chemotactic factors (IL-8). Melphalan increased monocytic adhesion to human retinal endothelial cells. Consistent with these in vitro findings, histopathology showed vessel wall endothelial cell changes, leukostasis, and vessel occlusion. Conclusions. These results reflect a direct interaction of chemotherapeutic drugs with both the vascular endothelium and monocytes. The vascular toxicity may be related to the pH, the pulsatile delivery, or the chemotherapeutic drugs used. Our long-term goal is to determine if changes in the drug of choice and/or delivery procedures will decrease vascular toxicity and lead to better eye-targeted treatment strategies.
Abstract
High-eccentricity tidal migration is a possible way for giant planets to be placed in short-period orbits. If this happens often, one would expect to catch proto hot Jupiters on highly ...elliptical orbits undergoing high-eccentricity tidal migration. As of yet, few such systems have been discovered. Here, we introduce TOI-3362b (TIC-464300749b), an 18.1 day, 5
M
Jup
planet orbiting a main-sequence F-type star that is likely undergoing high-eccentricity tidal migration. The orbital eccentricity is 0.815
−
0.032
+
0.023
. With a semimajor axis of 0.153
−
0.003
+
0.002
au, the planet’s orbit is expected to shrink to a final orbital radius of 0.051
−
0.006
+
0.008
au after complete tidal circularization. Several mechanisms could explain the extreme value of the planet’s eccentricity, such as planet–planet scattering and secular interactions. Such hypotheses can be tested with follow-up observations of the system, e.g., measuring the stellar obliquity and searching for companions in the system with precise, long-term radial-velocity observations. The variation in the planet’s equilibrium temperature as it orbits the host star and the tidal heating at periapse make this planet an intriguing target for atmospheric modeling and observation. Because the planet’s orbital period of 18.1 days is near the limit of TESS’s period sensitivity, even a few such discoveries suggest that proto hot Jupiters may be quite common.
For critically ill adults, oxygen saturation is continuously monitored using pulse oximetry (Spo
) as a surrogate for arterial oxygen saturation (Sao
). Skin pigmentation may affect accuracy of Spo
...by introducing error from statistical bias, variance, or both. We evaluated relationships between race, Spo
, Sao
, and hypoxemia (Sao
< 88%) or hyperoxemia (Pao
> 150 mm Hg) among adults receiving mechanical ventilation in a medical ICU.
Single-center, observational study.
Medical ICU at an academic medical center.
Critically ill adults receiving mechanical ventilation from July 2018 to February 2021, excluding patients with COVID-19, with race documented as Black or White in the electronic medical record, who had a pair of Spo
and Sao
measurements collected within 10 minutes of each other.
None.
We included 1,024 patients with 5,557 paired measurements within 10 minutes, of which 3,885 (70%) were within 1 minute. Of all pairs, 769 (14%) were from Black patients and 4,788 (86%) were from White patients. In analyses using a mixed-effects model, we found that across the range of Spo
values of 92-98%, the associated Sao
value was approximately 1% point lower for Black patients compared with White patients. Among patients with a Spo
value between 92% and 96%, Black patients were more likely to have both hypoxemia (3.5% vs 1.1%;
= 0.002) and hyperoxemia (4.7% vs 2.4%;
= 0.03), compared with White patients.
Among patients with a measured Spo
of 92-96%, greater variation in Sao
values at a given Spo
resulted in a higher occurence rate of both hypoxemia and hyperoxemia for Black patients compared with White patients.
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