Inflammatory bowel disease (IBD) is associated with alterations of the innate and adaptive immune systems. Monocytes respond to inflammation and infection, yet the relationship between monocytosis ...and IBD severity is not fully understood. We aimed to characterize the prevalence of monocytosis in IBD and the association between monocytosis and disease severity and IBD-related health care utilization.
We used a multiyear, prospectively collected natural history registry to compare patients with IBD with monocytosis to those without monocytosis, among all patients and by disease type.
A total of 1290 patients with IBD (64.1% with Crohn disease; 35.9% with ulcerative colitis) were included (mean age 46.4 years; 52.6% female). Monocytosis was found in 399 (30.9%) of patients with IBD (29.3% with Crohn disease; 33.9% with ulcerative colitis). Monocytosis was significantly associated with abnormal C-reactive protein level and erythrocyte sedimentation rate, anemia, worse quality of life, active disease, and increased exposure to biologics (all P < 0.001). Compared with patients without monocytosis, patients with monocytosis had a 3-fold increase in annual financial health care charges (median: $127,013 vs. $32,925, P < 0.001) and an increased likelihood of hospitalization (adjusted odds ratio AOR, 4.5; P < 0.001), IBD-related surgery (AOR, 1.9; P = 0.002), and emergency department (ED) use (AOR, 2.8; P < 0.001). Patients with monocytosis had a shorter time to surgery, hospitalization, and ED visit after stratifying by disease activity (all P < 0.05).
Patients with IBD with monocytosis, regardless of disease type, are at increased risk for worse clinical outcomes, hospitalization, surgery, and ED use. Peripheral monocytosis may represent a routinely available biomarker of a distinct subgroup with severe disease.
Mutations in RAS occur in 30–50% of metastatic colorectal carcinomas (mCRCs) and correlate with resistance to anti-EGFR therapy. Consequently, mCRC biomarker guidelines state RAS mutational testing ...should be performed when considering EGFR inhibitor treatment. However, a small subset of mCRCs are reported to harbor RAS amplification. In order to elucidate the clinicopathologic features and anti-EGFR treatment response associated with RAS amplification, we retrospectively reviewed a large cohort of mCRC patients that underwent targeted next-generation sequencing and copy number analysis for KRAS, NRAS, HRAS, BRAF, and PIK3CA. Molecular testing was performed on 1286 consecutive mCRC from 1271 patients as part of routine clinical care, and results were correlated with clinicopathologic findings, mismatch repair (MMR) status and follow-up. RAS amplification was detected in 22 (2%) mCRCs and included: KRAS, NRAS, and HRAS for 15, 5, and 2 cases, respectively (6–21 gene copies). Patients with a KRAS-amplified mCRC were more likely to report a history of inflammatory bowel disease (p < 0.001). In contrast, mutations in KRAS were associated with older patient age, right-sided colonic origin, low-grade differentiation, mucinous histology, and MMR proficiency (p ≤ 0.017). Four patients with a KRAS-amplified mCRC and no concomitant RAS/BRAF/PIK3CA mutations received EGFR inhibitor-based therapy, and none demonstrated a clinicoradiographic response. The therapeutic impact of RAS amplification was further evaluated using a separate, multi-institutional cohort of 23 patients. Eight of 23 patients with KRAS-amplified mCRC received anti-EGFR therapy and all 8 patients exhibited disease progression on treatment. Although the number of KRAS-amplified mCRCs is limited, our data suggest the clinicopathologic features associated with mCRC harboring a KRAS amplification are distinct from those associated with a KRAS mutation. However, both alterations seem to confer EGFR inhibitor resistance and, therefore, RAS testing to include copy number analyses may be of consideration in the treatment of mCRC.
IntroductionPrimary care providers play a critical role in reducing patients' risk for cardiovascular disease, including providing dietary counseling. However, few physicians feel adequately trained ...to provide this counseling, and most internal medicine (IM) residencies do not offer nutrition education. MethodsWe created an interactive, case-based activity for IM residents to improve the delivery of nutrition counseling to patients with hypertension, hyperlipidemia, overweight, and obesity. The curriculum was given over two in-person small-group sessions facilitated by physician preceptors. It reviewed evidence for relevant dietary patterns, provided resources for dietary referrals, and allowed residents to practice counseling based on a patient's stage of behavioral change. ResultsResidents completed electronic surveys prior to curriculum implementation, immediately after, and 2 months after completion of the curriculum. Aggregate percent correct scores of knowledge questions improved significantly in the immediate postsurvey (n = 24 paired responses, p = .004). We also reviewed electronic health records of patients with body mass index ≥ 25, hypertension, or hyperlipidemia who were seen in our resident clinics 2 months prior (n = 503) and 2 months after (n = 473) curriculum delivery. Residents' documented nutrition counseling increased from 35% to 41% (odds ratio, 1.27; 95% CI, 0.97-1.67; p = .085). DiscussionWe demonstrated improved knowledge of nutrition interventions to reduce cardiovascular risk and reported improvement of resident-provided nutrition counseling for appropriate patients. This activity offers IM residents effective initial nutrition training for patients at risk for cardiovascular disease and is practical to implement as part of an ambulatory curriculum.
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