Early M-Protein Dynamics Predicts Progression-Free Survival in Patients With Relapsed/Refractory Multiple Myeloma

This study aimed to predict long-term progression-free survival (PFS) using early M-protein dynamic measurements in patients with relapsed/refractory multiple myeloma (MM). The PFS was modeled based on dynamic M-protein data from two phase III studies, POLLUX and CASTOR, which included 569 and 498 patients with relapsed/refractory MM, respectively. Both studies compared active controls (lenalidomide and dexamethasone, and bortezomib and dexamethasone, respectively) alone vs. in combination with daratumumab. Three M-protein dynamic features from the longitudinal M-protein data were evaluated up to different time cutoffs (1, 2, 3, and 6 months). The abilities of early M-protein dynamic measurements to predict the PFS were evaluated using Cox proportional hazards survival models. Both univariate and multivariable analyses suggest that maximum reduction of M-protein (i.e., depth of response) was the most predictive of PFS. Despite the statistical significance, the baseline covariates provided very limited predictive value regarding the treatment effect of daratumumab. However, M-protein dynamic features obtained within the first 2 months reasonably predicted PFS and the associated treatment effect of daratumumab. Specifically, the areas under the time-varying receiver operating characteristic curves for the model with the first 2 months of M-protein dynamic data were ~ 0.8 and 0.85 for POLLUX and CASTOR, respectively. Early M-protein data within the first 2 months can provide a prospective and reasonable prediction of future long-term clinical benefit for patients with MM

Prevalence of abnormal radiographic findings in 2-year-old Thoroughbreds at in-training sales and associations with racing performance

Objective: To estimate the prevalence of radiographic abnormalities (lesions) in Thoroughbred racehorses at 2-year-old in-training sales and determine whether these lesions and 1-furlong presale workout times were associated with subsequent racing performance. Design: Retrospective cohort study. Animals: 953 Thoroughbreds. Procedures: Repository radiographs of carpal, metacarpophalangeal and metatarsophalangeal (fetlock), stifle, and tarsal (hock) joints were examined. Horses with lesions were classified by lesion type and location. Race performance variables were compared between horses with and without lesions and between horses categorized by 1-furlong presale workout times (< or ≥ 11 seconds). Results: 299 horses had ≥ 1 lesion, and 654 had no lesion detected. Odds of starting a race and of earning money racing were lower for horses with any lesion and lower for horses with proximal phalangeal dorsoproximal articular margin chip fracture, proximal sesamoid bone fracture or sesamoiditis, or wedge-shaped central or third tarsal bones, compared with horses that had no lesion. For horses that raced, proximal phalangeal dorsoproximal articular margin chip fractures were associated with lower lifetime earnings, and flattening of the medial femoral condyle was associated with fewer 3-year-old racing starts, compared with values for horses that had no lesion. Horses with workout times < 11 seconds had greater odds of having lifetime starts, lifetime earnings, and maximum purse above threshold (median) values than did horses with slower workout times. Conclusions and Clinical Relevance: No radiographic lesions prevented all affected horses from racing. Among horses that raced, few differences were found in performance for horses with and without lesions

Comparison of the use of scapular ultrasonography, physical examination, and measurement of serum biomarkers of bone turnover versus scintigraphy for detection of bone fragility syndrome in horses.

Objective: To define scintigraphic, physical examination, and scapular ultrasonographic findings consistent with bone fragility syndrome (BFS) in horses; develop indices of BFS severity; and assess accuracy of physical examination, scapular ultrasonography, and serum biomarkers for BFS diagnosis. Design: Prospective case-control study. Animals: 48 horses (20 horses with BFS and 28 control horses). Procedures: Horses underwent forelimb scintigraphic evaluation, physical examination, scapular ultrasonography, and serum collection. Scintigraphy was used as a reference standard to which physical examination, scapular ultrasonography, and concentrations of serum biomarkers (carboxy-terminal telopeptide of collagen crosslinks and bone-specific alkaline phosphatase activity) were compared for assessing accuracy in BFS diagnosis. Results: A diagnosis of BFS was strongly supported on scintigraphy by ≥ 2 regions of increased radiopharmaceutical uptake, including 1 region in the scapular spine and 1 region in the scapular body or ribs; on physical examination by lateral bowing of the scapulae; and on ultrasonography by widening of the scapular spine. None of the tests evaluated were accurate enough to replace scintigraphy for mild disease; however, physical examination and scapular ultrasonography were accurate in horses with moderate to severe BFS. Serum biomarkers were not accurate for BFS diagnosis. Conclusions and Clinical Relevance: Scintigraphy remained the most informative diagnostic modality for BFS, providing insight into disease severity and distribution; however, physical examination and scapular ultrasonographic abnormalities were diagnostic in horses with moderate to severe disease. Proposed severity indices classified the spectrum of disease manifestations. Clearly defined criteria for interpretation of diagnostic tests aid in the detection of BFS. Severity indices may be useful for assessing disease progression and response to treatment

Successful treatment of invasive pulmonary aspergillosis in a neonatal foal

No abstract available

Toward the improvement of total nitrogen deposition budgets in the United States

Frameworks for limiting ecosystem exposure to excess nutrients and acidity require accurate and complete deposition budgets of reactive nitrogen (Nr). While much progress has been made in developing total Nr deposition budgets for the U.S., current budgets remain limited by key data and knowledge gaps. Analysis of National Atmospheric Deposition Program Total Deposition (NADP/TDep) data illustrates several aspects of current Nr deposition that motivate additional research. Averaged across the continental U.S., dry deposition contributes slightly more (55%) to total deposition than wet deposition and is the dominant process (>90%) over broad areas of the Southwest and other arid regions of the West. Lack of dry deposition measurements imposes a reliance on models, resulting in a much higher degree of uncertainty relative to wet deposition which is routinely measured. As nitrogen oxide (NOx) emissions continue to decline, reduced forms of inorganic nitrogen (NHx = NH3 + NH4 +) now contribute >50% of total Nr deposition over large areas of the U.S. Expanded monitoring and additional process-level research are needed to better understand NHx deposition, its contribution to total Nr deposition budgets, and the processes by which reduced N deposits to ecosystems. Urban and suburban areas are hotspots where routine monitoring of oxidized and reduced Nr deposition is needed. Finally, deposition budgets have incomplete information about the speciation of atmospheric nitrogen; monitoring networks do not capture important forms of Nr such as organic nitrogen. Building on these themes, we detail the state of the science of Nr deposition budgets in the U.S. and highlight research priorities to improve deposition budgets in terms of monitoring and flux measurements, leaf- to regional-scale modeling, source apportionment, and characterization of deposition trends and patterns.</p