Citations

Purpose Patients with 1p/19q codeleted anaplastic oligodendroglial tumors who participated in RTOG (Radiation Therapy Oncology Group) 9402 lived much longer after chemoradiotherapy (CRT) than radiation therapy (RT) alone. However, some patients with noncodeleted tumors also benefited from CRT; survival curves separated after the median had been reached, and significantly more patients lived ≥ 10 years after CRT than RT. Thus, 1p/19q status may not identify all responders to CRT. Patients and Methods Using trial data, we inquired whether an IDH mutation or germ-line polymorphism associated with IDH-mutant gliomas identified the patients in RTOG 9402 who benefited from CRT. Results IDH status was evaluable in 210 of 291 patients; 156 (74%) had mutations. rs55705857 was evaluable in 245 patients; 76 (31%) carried the G risk allele. Both were associated with longer progression-free survival after CRT, and mutant IDH was associated with longer overall survival (9.4 v 5.7 years; hazard ratio [HR], 0.59; 95% CI, 0.40 to 0.86; P = .006). For those with wild-type tumors, CRT did not prolong median survival (1.3 v 1.8 years; HR, 1.14; 95% CI, 0.63 to 2.04; P = .67) or 10-year survival rate (CRT, 6% v RT, 4%). Patients with codeleted mutated tumors (14.7 v 6.8 years; HR, 0.49; 95% CI, 0.28 to 0.85; P = .01) and noncodeleted mutated tumors (5.5 v 3.3 years; HR, 0.56; 95% CI, 0.32 to 0.99; P < .05) lived longer after CRT than RT. Conclusion IDH mutational status identified patients with oligodendroglial tumors who did (and did not) benefit from alkylating-agent chemotherapy with RT. Although patients with codeleted tumors lived longest, patients with noncodeleted IDH-mutated tumors also lived longer after CRT.

Epstein-Barr virus (EBV) is a ubiquitous virus that commonly affects children and adolescents. In addition to causing a viral illness, it is also associated with various malignancies in particular B cell lymphomas and lymphoproliferative disorders. Differentiating between the two processes can be a diagnostic challenge. Here, we present a case of an atypical EBV infection in an elderly patient with severe systemic symptoms, multiorgan involvement, lymphadenopathy, and negative EBV serology. Excisional lymph node biopsy demonstrated features of a lymphoproliferative process involving EBV. Despite supportive care, she experienced continued clinical deterioration and was successfully treated with rituximab. This case illustrates the diagnostic challenges of these cases particularly in the elderly who may have age related immunosenescence, the utility of EBV PCR testing, and the clinical efficacy of rituximab in clearing the infected cells.

Background: The current systems of healthcare delivery in the United States suffer from problems that often leave patients with inadequate quality of care. In their report entitled “Crossing the Quality Chasm,” the Institute of Medicine (IOM) identified reasons for poor and/or inconsistent quality of healthcare delivery and provided recommendations to improve it. The purpose of this review is to describe features of an innovative web-based program called the Thyroid Cancer Care Collaborative (TCCC) and see how it addresses IOM recommendations to improve the quality of healthcare delivery. Summary: The TCCC addresses the three actionable IOM recommendations directed at healthcare organizations and clinicians to redesign the care process. It does so by exploiting information technology (IT) in ways suggested by the IOM, and it fits within a set of 10 rules provided by the IOM. Some features of the TCCC include: (i) automated disease staging based on three validated scoring systems; (ii) highly illustrated educational videos on all aspects of thyroid cancer care; (iii) personalized clinical decision-making modules for clinicians and physicians; (iv) portability of data to share among treating physicians; (v) virtual tumor boards, “ask the expert,” and frequently asked questions modules; (vi) physician workflow integration; and (vii) data for comprehensive analysis to answer difficult questions in thyroid cancer management. Conclusion: The TCCC has the potential to improve thyroid cancer care delivery and offers several benefits to patients, clinicians, and researchers. The TCCC is a valuable example of how IOM initiatives can improve the healthcare system.

The ionic liquid N‐ethyl‐N′‐methyl imidazolium chloride (EMIMCl) has been described as being very efficient in promoting refolding of the recombinant plasminogen activator rPA. Our study reveals that molar concentrations of EMIMCl increase the solubility of native and unfolded proteins due to favorable interactions with amino acid side chains rather than favorably interacting with the peptide backbone. This delicate balance of favorable interactions with side chains and unfavorable interactions with the peptide backbone provides a molecular explanation of how EMIMCl suppresses protein aggregation and simultaneously promotes refolding. By contrast, high concentrations of EMIMCl denature proteins because of a reduced water content and strong favorable interactions with amino acid side chains. This denatured species is not soluble and aggregates because, in contrast to the classical denaturants, guanidine hydrochloride and urea, EMIMCl does not solubilize the peptide backbone.Structured digital abstract PNP and PNP bind by molecular sieving (1, 2, 3, 4)

Obesity associated with metabolic derangements (ObM) worsens the prognosis of patients with coronary artery stenosis (CAS), but the underlying cardiac pathophysiologic mechanisms remain elusive. We tested the hypothesis that ObM exacerbates cardiomyocyte loss distal to moderate CAS. Obesity-prone pigs were randomized to four groups ( n = 6 each): lean-sham, ObM-sham, lean-CAS, and ObM-CAS. Lean and ObM pigs were maintained on a 12-wk standard or atherogenic diet, respectively, and left circumflex CAS was then induced by placing local-irritant coils. Cardiac structure, function, and myocardial oxygenation were assessed 4 wk later by computed-tomography and blood oxygenation level dependent (BOLD) MRI, the microcirculation with micro-computed-tomography, and injury mechanisms by immunoblotting and histology. ObM pigs showed obesity, dyslipidemia, and insulin resistance. The degree of CAS (range, 50–70%) was similar in lean and ObM pigs, and resting myocardial perfusion and global cardiac function remained unchanged. Increased angiogenesis distal to the moderate CAS observed in lean was attenuated in ObM pigs, which also showed microvascular dysfunction and increased inflammation (M1-macrophages, TNF-α expression), oxidative stress (gp91), hypoxia (BOLD-MRI), and fibrosis (Sirius-red and trichrome). Furthermore, lean-CAS showed increased myocardial autophagy, which was blunted in ObM pigs (downregulated expression of unc-51-like kinase-1 and autophagy-related gene-12; P < 0.05 vs. lean CAS) and associated with marked apoptosis. The interaction diet xstenosis synergistically inhibited angiogenic, autophagic, and fibrogenic activities. ObM exacerbates structural and functional myocardial injury distal to moderate CAS with preserved myocardial perfusion, possibly due to impaired cardiomyocyte turnover.