Citations

Objective The link and interplay between different airway exposures and rheumatoid arthritis (RA) risk are unclear. This study was undertaken to determine whether respiratory disease is associated with development of RA, and specifically to examine this relationship by RA serostatus and smoking exposure. Methods Using data from the Epidemiological Investigation of Rheumatoid Arthritis study, this analysis included 1,631 incident RA cases and 3,283 matched controls recruited from 2006 to 2016. Linking these individuals to the National Patient Register provided information on past acute or chronic, upper or lower respiratory disease diagnoses. For each disease group, we estimated adjusted odds ratios (OR adj ) with 95% confidence intervals (95% CI) for RA, using logistic regression models adjusted for age, sex, residential area, body mass index, and education both overall and stratified by anti–citrullinated protein antibody (ACPA)/rheumatoid factor (RF) status and by smoking status. Results Respiratory disease diagnoses were associated with risk of RA, with an OR adj of 1.2 for acute upper respiratory disease (95% CI 0.8–1.7), 1.4 for chronic upper respiratory disease (95% CI 1.1–1.9), 2.4 for acute lower respiratory disease (95% CI 1.5–3.6), and 1.6 for chronic lower respiratory disease (95% CI 1.5–3.6). These associations were present irrespective of RF or ACPA status, though the association was somewhat stronger for ACPA/RF–positive than ACPA/RF–negative RA. The association between any respiratory disease and RA was stronger for nonsmokers (OR adj 2.1 [95% CI 1.5–2.9]) than for smokers (OR adj 1.2 [95% CI 0.9–1.5]). Conclusion Respiratory diseases increase the risk for both seropositive and seronegative RA, but only among nonsmokers. These findings raise the hypothesis that smoking and airway disease are associated with RA development through partly different mechanisms.

In 2018, the American Board of Anesthesiology (ABA) became the first US medical specialty certifying board to incorporate an Objective Structured Clinical Examination (OSCE) into its initial certification examination system. Previously, the ABA’s staged examination system consisted of 2 written examinations (the BASIC and ADVANCED examinations) and the Standardized Oral Examination (SOE). The OSCE and the existing SOE are now 2 separate components of the APPLIED Examination. This report presents the results of the first-year OSCE administration. A total of 1410 candidates took both the OSCE and the SOE in 2018. Candidate performance approximated a normal distribution for both the OSCE and the SOE, and was not associated with the timing of the examination, including day of the week, morning versus afternoon session, and order of the OSCE and the SOE. Practice-based Learning and Improvement was the most difficult station, while Application of Ultrasonography was the least difficult. The correlation coefficient between SOE and OSCE scores was 0.35 ([95% confidence interval {CI}, 0.30–0.39]; P < .001). Scores for the written ADVANCED Examination were modestly correlated with scores for the SOE ( r = 0.29 [95% CI, 0.25–0.34]; P < .001) and the OSCE ( r = 0.15 [95% CI, 0.10–0.20]; P < .001). Most of the candidates who failed the SOE passed the OSCE, and most of the candidates who failed the OSCE passed the SOE. Of the 1410 candidates, 77 (5.5%) failed the OSCE, 155 (11.0%) failed the SOE, and 25 (1.8%) failed both. Thus, 207 (14.7%) failed at least 1 component of the APPLIED Examination. Adding an OSCE to a board certification examination system is feasible. Preliminary evidence indicates that the OSCE measures aspects of candidate abilities distinct from those measured by other examinations used for initial board certification.

There is no evidence-based definition for diagnosing crescentic glomerulonephritis. The prognostic implications of crescentic lesions on kidney biopsy have not been quantified. Our objective was to determine risk factors for end-stage kidney disease (ESKD) in patients with glomerulonephritis and crescents on kidney biopsy. A query of the Pediatric Nephrology Research Consortium’s Pediatric Glomerulonephritis with Crescents registry identified 305 patients from 15 centers. A retrospective cohort study was performed with ESKD as the primary outcome. Median age at biopsy was 11 years (range 1–21). The percentage of crescents was 3–100% (median 20%). Etiologies included IgA nephropathy (23%), lupus (21%), IgA vasculitis (19%) and ANCA-associated GN (13%), post-infectious GN (5%), and anti-glomerular basement membrane disease (3%). The prevalence of ESKD was 12% at one year and 16% at last follow-up (median = 3 years, range 1–11). Median time to ESKD was 100 days. Risk factors for ESKD included %crescents, presence of fibrous crescents, estimated GFR, and hypertension at biopsy. For each 1% increase in %crescents, there was a 3% decrease in log odds of 1-year renal survival (p = 0.003) and a 2% decrease in log odds of renal survival at last follow-up (p < 0.001). These findings provide an evidence base for enrollment criteria for crescentic glomerulonephritis in future clinical trials.

PURPOSENRG Oncology/RTOG 9802 (ClinicalTrials.gov Identifier: NCT00003375 ) is a practice-changing study for patients with WHO low-grade glioma (LGG, grade II), as it was the first to demonstrate a survival benefit of adjuvant chemoradiotherapy over radiotherapy. This post hoc study sought to determine the prognostic and predictive impact of the WHO-defined molecular subgroups and corresponding molecular alterations within NRG Oncology/RTOG 9802.METHODSIDH1/2 mutations were determined by immunohistochemistry and/or deep sequencing. A custom Ion AmpliSeq panel was used for mutation analysis. 1p/19q codeletion and MGMT promoter methylation were determined by copy-number arrays and/or Illumina 450K array, respectively. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using the Cox proportional hazard model and tested using the log-rank test. Multivariable analyses (MVAs) were performed incorporating treatment and common prognostic factors as covariates.RESULTSOf the eligible patients successfully profiled for the WHO-defined molecular groups (n = 106/251), 26 (24%) were IDH-wild type, 43 (41%) were IDH-mutant/non-codeleted, and 37(35%) were IDH-mutant/codeleted. MVAs demonstrated that WHO subgroup was a significant predictor of PFS after adjustment for clinical variables and treatment. Notably, treatment with postradiation chemotherapy (PCV; procarbazine, lomustine (CCNU), and vincristine) was associated with longer PFS (HR, 0.32; P = .003; HR, 0.13; P < .001) and OS (HR, 0.38; P = .013; HR, 0.21; P = .029) in the IDH-mutant/non-codeleted and IDH-mutant/codeleted subgroups, respectively. In contrast, no significant difference in either PFS or OS was observed with the addition of PCV in the IDH-wild-type subgroup.CONCLUSIONThis study is the first to report the predictive value of the WHO-defined diagnostic classification in a set of uniformly treated patients with LGG in a clinical trial. Importantly, this post hoc analysis supports the notion that patients with IDH-mutant high-risk LGG regardless of codeletion status receive benefit from the addition of PCV.

Abstract Techniques that enable longitudinal tracking of cell fate after myocardial delivery are imperative for optimizing the efficacy of cell-based cardiac therapies. However, these approaches have been underutilized in preclinical models and clinical trials, and there is considerable demand for site-specific strategies achieving long-term expression of reporter genes compatible with safe noninvasive imaging. In this study, the rhesus sodium/iodide symporter (NIS) gene was incorporated into rhesus macaque induced pluripotent stem cells (RhiPSCs) via CRISPR/Cas9. Cardiomyocytes derived from NIS-RhiPSCs (NIS-RhiPSC-CMs) exhibited overall similar morphological and electrophysiological characteristics compared to parental control RhiPSC-CMs at baseline and with exposure to physiological levels of sodium iodide. Mice were injected intramyocardially with 2 million NIS-RhiPSC-CMs immediately following myocardial infarction, and serial positron emission tomography/computed tomography was performed with 18F-tetrafluoroborate to monitor transplanted cells in vivo. NIS-RhiPSC-CMs could be detected until study conclusion at 8 to 10 weeks postinjection. This NIS-based molecular imaging platform, with optimal safety and sensitivity characteristics, is primed for translation into large-animal preclinical models and clinical trials.

ObjectiveGiant cell arteritis (GCA) is a large‐vessel vasculitis that primarily affects the aorta and its branches. Extracranial branches of the carotid artery are frequently affected; however, intracranial involvement in GCA is rare.MethodsA retrospective medical record review was performed to identify all patients with intracranial GCA (IC‐GCA) from January 1996 through May 2018.ResultsNine patients with IC‐GCA were included (78% male; mean age, 72.1 years [SD: 7.9]). All patients met ACR criteria for GCA. The median time from onset of GCA to intracranial involvement was 0.6 months (interquartile range: 0.1‐5.1). All patients had neurologic symptoms, 89% had an ischemic cerebrovascular event. Transient or permanent vision loss was frequent (56% of patients). IC‐GCA was diagnosed by cranial imaging in all nine patients. Intracranial vasculitis most commonly affected the internal carotid artery (100%), followed by the vertebral artery (67%), posterior cerebral artery (67%), middle cerebral artery (44%), anterior cerebral artery (33%), and posterior inferior cerebral artery (11%). Intracranial vessel stenosis was present in 89%, occlusion in 33%, wall thickening in 33%, and dilation in 11%.All patients received glucocorticoids. Additional therapeutic agents included cyclophosphamide (67%) and tocilizumab (22%). Despite treatment, five patients had rapid deterioration and mortality. Comparing IC‐GCA patient survival to the expected rates from the US population, the standardized mortality ratio (95% CI) for IC‐GCA was 58.1 (18.9‐135.6).ConclusionAlthough rare, IC‐GCA is associated with significant morbidity and mortality. It occurs predominantly in men and presents with ischemic cerebrovascular events. Current treatment strategies appear to be of limited efficacy for IC‐GCA.

ObjectiveTo examine the impact of treatment on disease‐specific health‐related quality of life (HRQOL) among patients with sporadic vestibular schwannoma (VS).Study DesignNational cross‐sectional study.SettingTertiary referral center and the Acoustic Neuroma Association.Subjects and MethodsAdult patients with VS who completed the Penn Acoustic Neuroma Quality of Life (PANQOL) survey. Patients were classified by treatment at the most recent survey as microsurgery, radiosurgery, observation, or recently diagnosed (RD). PANQOL scores were compared among VS treatment groups and with nontumor controls using analysis of covariance.ResultsA total of 1362 respondents with VS were analyzed. Total PANQOL scores differed significantly by treatment (P =. 024) with adjusted means of 60, 63, 65, and 62 for the microsurgery, radiosurgery, observation, and RD groups, respectively. Subdomain scores for facial function, balance, hearing loss, and pain differed significantly (P <. 05) by treatment. Comparisons that surpassed thresholds for clinical significance included microsurgery compared to radiosurgery and observation for facial function, microsurgery compared to observation and RD for hearing loss, and microsurgery compared to radiosurgery and observation for pain. Subdomain scores for anxiety, facial function, balance, hearing loss, energy, and pain and total PANQOL scores for nontumor controls were significantly higher (ie, more favorable) compared to the VS groups (P <. 05). General health scores did not differ significantly between the nontumor controls and the VS groups (P =. 19).ConclusionDifferences in HRQOL among treatment modalities are small and variably exceed the minimal clinically important difference. The impact of a VS diagnosis on HRQOL supersedes that of the treatment type.

PURPOSE To update the ASCO guideline on the recommended prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors. METHODS An Expert Panel conducted targeted systematic literature reviews to identify new studies. RESULTS The search strategy identified 257 new references, which led to a full-text review of 87 manuscripts. A total of 3 systematic reviews, 2 with meta-analyses, and 28 primary trials for prevention of CIPN in addition to 14 primary trials related to treatment of established CIPN, are included in this update. RECOMMENDATIONS The identified data reconfirmed that no agents are recommended for the prevention of CIPN. The use of acetyl-l-carnitine for the prevention of CIPN in patients with cancer should be discouraged. Furthermore, clinicians should assess the appropriateness of dose delaying, dose reduction, substitutions, or stopping chemotherapy in patients who develop intolerable neuropathy and/or functional impairment. Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited. Additional information is available at www.asco.org/survivorship-guidelines .