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Purpose This study addressed whether age is prognostic for overall survival (OS) or progression-free survival (PFS) in patients with metastatic colorectal cancer (mCRC). Patients and Methods A total of 20,023 patients from 24 first-line clinical trials in the ARCAD (Aide et Recherche en Cancérologie Digestive) database were analyzed. Primary age effects and interactions with age, sex, performance status (PS), and metastatic site were modeled using Cox proportional hazards stratified by treatment arm within study. Results Of total patients, 3,051 (15%) were age ≤ 50 years. Age was prognostic for both OS (P < .001) and PFS (P < .001), with U-shaped risk (ie, highest risk was evident in youngest and oldest patients). Relative to patients of middle age, the youngest patients experienced 19% (95% CI, 7% to 33%) increased risk of death and 22% (95% CI, 10% to 35%) increased risk of progression. The oldest patients experienced 42% (95% CI, 31% to 54%) increased risk of death and 15% (95% CI, 7% to 24%) increased risk of progression or death. This relationship was more pronounced in the first year of follow-up. Age remained marginally significant for OS (P = .08) when adjusted for PS, sex, and presence of liver, lung, or peritoneal metastases, and age was significant in an adjusted model for PFS (P = .005). The age effect did not differ by site of metastatic disease, year of enrollment, type of therapy received, or biomarker mutational status. Conclusion Younger and older age are associated with poorer OS and PFS among treated patients with mCRC. Younger and older patients may represent higher-risk populations, and additional studies are warranted.

Abstract INTRODUCTION High-sensitivity cardiac troponin assays have potent prognostic value in stable cardiovascular disease cohorts. Our objective was to assess the prognostic utility of a novel cardiac troponin I (cTnI) high-sensitivity assay, independently and in combination with amino-terminal pro–B-type natriuretic peptide (NT-proBNP), for the future development of heart failure and mortality in the general community. METHODS A well-characterized community-based cohort of 2042 participants underwent clinical assessment and echocardiographic evaluation. Baseline measurements of cTnI with a high-sensitivity assay and NT-proBNP were obtained in 1843 individuals. Participants were followed for new-onset heart failure and mortality with median (25th, 75th percentile) follow-up of 10.7 (7.9, 11.6) and 12.1 (10.4, 13.0) years, respectively. RESULTS When measured with a high-sensitivity assay, cTnI greater than the sex-specific 80th percentile was independently predictive of heart failure [hazard ratio 2.56 (95% confidence interval 1.88–3.50), P &lt; 0.001] and mortality [1.91(1.49–2.46), P &lt; 0.001] beyond conventional risk factors in this community-based cohort, with significant increases in the net reclassification improvement for heart failure. The prognostic utility of cTnI measured with a high-sensitivity assay goes beyond NT-proBNP, yet our data suggest that these 2 assays are complementary and most beneficial when evaluated together in identifying at-risk individuals in the community. CONCLUSIONS Our findings lay the foundation for prospective studies aimed at identification of individuals at high risk by use of a multimarker approach, followed by aggressive prevention strategies to prevent subsequent heart failure.

Lymphoma may affect the ureter in cases of retroperitoneal involvement. We present a case of an adolescent male found to have non-Hodgkin lymphoma initially presenting as ureteral stricture evident on imaging. He was treated and responded to multiagent chemotherapy with resolution of both the lymphoma and the ureteral stricture. Although rare, non-Hodgkin lymphoma should be included in the differential diagnosis of pediatric patients with noncalculous, idiopathic ureteral strictures.

OBJECTIVES: ImproveCareNow (ICN) is the largest pediatric learning health system in the nation and started as a quality improvement collaborative. To test the feasibility and validity of using ICN data for clinical research, we evaluated the effectiveness of anti-tumor necrosis factor-α (anti-TNFα) agents in the management of pediatric Crohn disease (CD). METHODS: Data were collected in 35 pediatric gastroenterology practices (April 2007 to March 2012) and analyzed as a sequence of nonrandomized trials. Patients who had moderate to severe CD were classified as initiators or non-initiators of anti-TNFα therapy. Among 4130 patients who had pediatric CD, 603 were new users and 1211 were receiving anti-TNFα therapy on entry into ICN. RESULTS: During a 26-week follow-up period, rate ratios obtained from Cox proportional hazards models, adjusting for patient and disease characteristics and concurrent medications, were 1.53 (95% confidence interval [CI], 1.20–1.96) for clinical remission and 1.74 (95% CI, 1.33–2.29) for corticosteroid-free remission. The rate ratio for corticosteroid-free remission was comparable to the estimate produced by the adult SONIC study, which was a randomized controlled trial on the efficacy of anti-TNFα therapy. The number needed to treat was 5.2 (95% CI, 3.4–11.1) for clinical remission and 5.0 (95% CI, 3.4–10.0) for corticosteroid-free remission. CONCLUSIONS: In routine pediatric gastroenterology practice settings, anti-TNFα therapy was effective at achieving clinical and corticosteroid-free remission for patients who had Crohn disease. Using data from the ICN learning health system for the purpose of observational research is feasible and produces valuable new knowledge.

AbstractBackgroundThere is symptom overlap between gastro‐esophageal reflux disease (GERD) and functional dyspepsia (FD). We aimed to test the hypothesis that FD cases are now more likely mislabeled as GERD.MethodsIn subjects from Olmsted County, MN seen at Mayo Clinic: (i) Investigation of GERD and FD diagnosis rates between 1985 and 2009. (ii) Assessment of survey‐based upper gastrointestinal symptoms between 1988 and 2009. (iii) Analysis of patients reporting GERD and/or FD symptoms and subsequently receiving a consistent diagnosis of GERD and/or FD during a medical encounter. (iv) Assess the association between PPI use and GERD and/or FD symptoms and between actual diagnoses received.Key Results(i) Yearly GERD diagnosis rates rose between 1985 and 2009 (325–1866 per 100 000). FD diagnosis rates rose from 45 in 1985, to 964 in 1999 but decreased to 452 per 100 000 in 2009. (ii) Reported GERD symptoms did not significantly change between three survey waves in the years 1988–2009 (p = 0.052), whereas FD symptoms slightly increased (p = 0.01). (iii) 62.9% of subjects reporting GERD symptoms received a GERD diagnosis, however only 12.5% of subjects reporting FD symptoms received a FD diagnosis. (iv) PPI use was associated with documented GERD diagnosis (p < 0.001), however there was no significant association between GERD symptoms and PPI use (p = 0.078).Conclusions & InferencesWe have found evidence supporting a systematic bias away from diagnosing FD, favoring a GERD diagnosis.

AbstractObjectivesPatient throughput is an increasingly important cause of emergency department (ED) crowding. The authors previously reported shorter patient length of stay (LOS) when adding a triage liaison provider, which required additional personnel. Here, the objective was to evaluate the effect of moving a fast‐track provider to the triage liaison role.MethodsThis was a prospective observational before‐and‐after study design with predefined outcomes measures. A “standard staffing” situation (where an advanced practice provider staffed treatment rooms in the fast track) was compared with an advanced practice provider performing the triage liaison staffing role, with no additional staff. Eleven intervention (“triage liaison staffing”) days were compared with 11 matched control (“standard staffing”) days immediately preceding the intervention. Total LOS was measured for all adult Emergency Severity Index (ESI) 3, 4, and 5 patients (excluding behavioral health patients), and results were compared using Wilcoxon rank‐sum and chi‐square tests.ResultsA total of 681 patients registered on control days and 599 on intervention days. There was no significant difference in total patient LOS: median = 273 minutes, interquartile range (IQR) 176 to 384 minutes on intervention days versus median = 253 minutes, IQR = 175 to 365 minutes on control days (p = 0.20). There was no difference in left‐without‐being‐seen (LWBS) rates (n = 48, 7% on control days vs. n = 35, 6% on intervention days; p=0.38). Secondary analysis of only ESI 3 patients showed no difference in total LOS between periods (median = 284 minutes, IQR = 194 to 396 minutes on intervention days vs. median = 290 minutes, IQR = 217 to 397 minutes on control days; p = 0.22). There was, however, significantly greater total LOS for ESI 4 and 5 patients during the intervention period (median = 238 minutes, IQR = 124 to 350 minutes on intervention days vs. median = 192 minutes, IQR = 124 to 256 minutes on control days; p = 0.011).ConclusionsThe previously reported benefits on patient LOS and LWBS rates after adding a triage liaison (resource additive) were lost when that provider was moved from fast track to the triage role (resource neutral). While the triage liaison provider role may be a way to improve ED throughput when additional resources are available, as evidenced by our prior study, the triage liaison model itself does not appear to replace the staffing of treatment rooms, as evidenced by this study.

Renal Vein Stimulation Increases Blood PressureBackgroundNeurocardiogenic syncope (NCS) is a common and sometimes debilitating disorder, with no consistently effective treatment. NCS is due to a combination of bradycardia and vasodilation leading to syncope. Although pacemaker devices have been tried in treating the bradycardic aspect of NCS, no device‐based therapy exists to treat the coexistent vasodilation that occurs. The renal sympathetic innervation has been the target of denervation to treat hypertension. We hypothesized that stimulation of the renal sympathetic nerves can increase blood pressure and counteract vasodilation in NCS.Methods and ResultsHigh‐frequency stimulation (800–900 pps, 10 V, 30–200 seconds) was performed using a quadripolar catheter in the renal vein of 7 dogs and 1 baboon. A significant increase in blood pressure (BP; mean [SD] systolic BP 117 [±28] vs. 128 [±33], diastolic BP 75 [±19] vs. 87 [±29] mmHg) was noted during the stimulation, which returned to baseline after cessation of stimulation. The mean increase in systolic and diastolic BP was 13.0 (±3.3) (P = 0.006) and 10.2 (±4.6) (P = 0.08), respectively.ConclusionWe report the first ever study of feasibility and safety of high‐frequency electrical stimulation of the renal sympathetic innervation to increase BP in animal models. This has potential applications in the treatment of hypotensive states such as NCS.