Activity

Immunohistochemical staining for synaptophysin and chromogranin was diffusely positive in 9 cases and focal in 1 case, and the Ki-67 proliferation index was 5% or less in all tumors. Follow-up ranged from 37 to 137 months (mean = 82; median = 77), and there was no evidence of residual disease or recurrence in any of the 10 patients during the follow-up period.Using data (2655 observations from 928 participants) from the Chronic Kidney Disease in Children Study, we developed and internally validated new glomerular filtration rate estimating equations for clinical use in children and young adults two forms of K × [heigh(ht) / serum creatinine(sCr)] and two forms of K × [1 / cystatin C(cysC)]. For each marker, one equation used a sex-dependent K; in the other, K is sex-and age-dependent. Glomerular filtration rate (GFR) was measured directly by plasma iohexol disappearance. The equations using ht⁄sCr had sex-specific constants of 41.8 for males and 37.6 for females. In the age- dependent models, K increased monotonically for children 1-18 years old and was constant for young adults 18-25 years. For males, K ranged from 35.7 for one-year-olds to 50.8 for those 18 and older. For females, the values of K ranged from 33.1 to 41.4. Constant K values for cystatin-C equations were 81.9 for males and 74.9 for females. With age-dependency, K varied non-monotonically with the highest values at age 15 for males (K of 87.2) and 12 years for females (K of 79.9). Use of an age-dependent K with ht/sCr models reduced average bias, notably in young children and young adults; age-dependent cystatin-C models produced similar agreement to using a constant K in children under 18 years, but reduced bias in young adults. These age-dependent proposed equations were evaluated alongside estimated GFRs from 11 other published equations for pediatrics and young adults. Only our proposed equations yielded non- significant bias and within 30% accuracy values greater than 85% in both the pediatric and young adult subpopulations.NMR relaxation dispersion measurements report on conformational changes occurring on the μs-ms timescale. Chemical shift information derived from relaxation dispersion can be used to generate structural models of weakly populated alternative conformational states. Current methods to obtain such models rely on determining the signs of chemical shift changes between the conformational states, which are difficult to obtain in many situations. Here, we use a “sample and select” method to generate relevant structural models of alternative conformations of the C-terminal-associated region of Escherichia coli dihydrofolate reductase (DHFR), using only unsigned chemical shift changes for backbone amides and carbonyls (1H, 15N, and 13C’). We find that CS-Rosetta sampling with unsigned chemical shift changes generates a diversity of structures that are sufficient to characterize a minor conformational state of the C-terminal region of DHFR. The excited state differs from the ground state by a change in secondary structure, consistent with previous predictions from chemical shift hypersurfaces and validated by the x-ray structure of a partially humanized mutant of E. coli DHFR (N23PP/G51PEKN). The results demonstrate that the combination of fragment modeling with sparse chemical shift data can determine the structure of an alternative conformation of DHFR sampled on the μs-ms timescale. Such methods will be useful for characterizing alternative states, which can potentially be used for in silico drug screening, as well as contributing to understanding the role of minor states in biology and molecular evolution.

Relapse is the most common cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT). No standard of care exists, and a wide range of treatments are used for post-alloHCT relapse. In the recent era, several novel therapies including targeted agents are available for acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), and myelodysplastic syndrome (MDS).

We reviewed outcomes after alloHCT relapse, with or without use of these newer agents for ALL, AML, and MDS. Z-VAD-FMK In total, 115 adults with relapsed or refractory ALL (n=17), AML (n=67), and MDS (n=31) at median 5 (range, 1-64) months after their first alloHCT in 2010-2018 were included.

Median follow-up was 19 (range, 6-80) months after relapse from alloHCT. Targeted agents were given to 29 (25%) patients. In multivariable analysis, use of targeted agent at any time point after relapse was not associated with survival. Matched unrelated (vs. matched sibling; hazard ratio [HR] 1.70; p=.027) or haploidentical donor grafts (vs. matched sibling; HR 2.69; p=.003), presence of grade II-IV acute graft-versus-host disease before relapse (HR 2.46; p<.001), and less than 12months from HCT to relapse (<6 vs.>12months; HR 6.34; p<.001; 6-12 vs.>12months; HR 3.16; p=.005) were adverse prognostic factors for post-relapse survival.

Outcomes after alloHCT relapse remain poor regardless of the novel agent use. Innovative treatment strategies are needed to improve outcomes after relapse post-alloHCT.

Outcomes after alloHCT relapse remain poor regardless of the novel agent use. Innovative treatment strategies are needed to improve outcomes after relapse post-alloHCT.

The primary curative treatment for thymic malignancies is surgery. For lung and esophageal cancer, substantive disparities in outcomes by race exist. Many of these disparities are attributed to the decreased use of surgery in non-White patients. Although thymic malignancies are treated by the same specialists as lung and esophageal cancer, it is unknown if there are racial disparities in the treatment of thymic malignancies.

Do racial disparities exist in the surgical treatment of thymic malignancies?

A retrospective cohort analysis was performed using the National Cancer Data Base of patients diagnosed with thymoma and thymic carcinoma between 2004 and 2016. Univariate comparisons of demographics were compared using χ

and rank-sum tests. Multivariable analysis was performed to determine if race was an independent variable associated with receiving surgical resection. Preoperative and postoperative care was compared between races.

Seven thousand four hundred eighty-nine patients met inclusion criteria.