Precision nicotine metabolism-informed care for smoking cessation in Crohn's disease: A pilot study.

INTRODUCTION: Smoking is a strong risk factor for disease severity in Crohn's disease (CD) and cessation improves outcomes. The nicotine metabolite ratio (NMR) predicts cessation success with pharmacotherapy: varenicline doubles cessation over nicotine replacement therapy (NRT) for "normal", but not "slow" metabolizers. Varenicline side effects are heightened in slow metabolizers. Methods using NMR to optimize cessation pharmacotherapy have not been evaluated in CD. AIMS: We aim to determine the prevalence of smoking in a CD population and then assess these smokers' attitudes toward a personalized metabolism-informed care (MIC) approach to cessation. METHODS: In this observational study, we surveyed 1098 patients visiting an inflammatory bowel disease center about their smoking history. We then evaluated a subgroup of individuals with CD (n = 32) who participated in a randomized controlled trial of smoking cessation using MIC versus usual care. For MIC, medication selection was informed by the NMR (normal ≥0.31 vs. slow <0.31). The primary outcomes were intervention satisfaction and match rates between NMR and medication choice. RESULTS: The baseline prevalence of smoking in our CD population was 13%. Intervention participants reported high rates of satisfaction (85%) and chose a medication that matched their NMR result more often in the MIC group (100% vs. 64%, p = 0.01). Six of 16 (37.5%) patients prescribed varenicline discontinued due to side effects. CONCLUSION: MIC produced high rates of satisfaction and matching between NMR and medication in CD patients, supporting patient acceptance and feasibility of precision smoking cessation in this population. To reduce smoking in CD, therapies such as MIC are needed to maximize efficacy and minimize side effects.

Esophageal Perforations: An Endoscopic Approach to Management.

PURPOSE OF REVIEW: Esophageal perforations are associated with high morbidity and mortality. As opposed to surgical repair, endoscopic closure techniques have emerged over the years as a more minimally invasive approach for management. Our goal is to discuss different modalities for closure. RECENT FINDINGS: Through-the-scope clips (TTSCs), over-the-scope clips (OTSCs), and esophageal stent placement are well known options for closure. We will also discuss the more recent technique of endoscopic suturing for closure of larger defects as well as prevention of esophageal stent migration. For mediastinal collections associated with perforations, a more novel endoluminal vacuum therapy (EVT) for drainage may be an option. Overall, there are several different endoscopic options that can tailored to the specific features of an esophageal perforation. This review will discuss various techniques with which a gastroenterologist or thoracic surgeon should be familiar.

Sarcopenia Is Common in Overweight Patients with Inflammatory Bowel Disease and May Predict Need for Surgery.

BACKGROUND: Inflammatory bowel disease (IBD) is associated with altered body composition, such as low muscle mass, which affects clinical outcomes. Body composition changes in overweight patients with IBD are less understood. The study aim was to determine the prevalence of sarcopenic overweight and obese patients in a cohort of patients with IBD starting new anti-tumor necrosis factor-α therapy and examine differences in response. METHODS: This is a retrospective review of patients with IBD starting a new anti-tumor necrosis factor-α medication that had computed tomography within 3 months of initiation. L3 vertebral slice was used for segmentation of body composition and identification of sarcopenia. CRP, ESR, Harvey Bradshaw Index, albumin, 25-OH vitamin D, and body mass index at anti-tumor necrosis factor-α initiation and at 6 months were collected. Outcomes included hospitalization, need for surgery, or new biological medication. RESULTS: Ninety patients were studied. Forty-one of ninety (45%) were sarcopenic; of these, 17 (41.5%) had a normal body mass index and 8 (19.5%) were overweight/obese. More men were sarcopenic (68% versus 32%, P < 0.001). CRP was higher and albumin lower in sarcopenic subjects. Sarcopenia did not predict outcomes in the cohort but was the only significant predictor of need for surgery in overweight and obese subjects (P = 0.002). CONCLUSIONS: Almost half of our cohort was sarcopenic. Most of these patients are normal or overweight and would not be identified as malnourished by traditional measures. Sarcopenia was a predictor of surgery in patients with a body mass index ≥ 25. Identification of sarcopenia has implications for medical nutrition therapy as typically efforts are focused on underweight patients.

T-cell derived interferon-gamma contributes to arteriolar dysfunction during acute hypercholesterolemia.

OBJECTIVES: T-lymphocytes and interferon-gamma (IFN-gamma) contribute to leukocyte recruitment in postcapillary venules during hypercholesterolemia. Our objectives were to determine whether: (1) T-lymphocytes are the source of this IFN-gamma, and (2) whether T-cell-derived IFN-gamma also mediates the accompanying arteriolar dysfunction and platelet adhesion. METHODS AND RESULTS: Intravital videomicroscopy was used to quantify arteriolar responses to acetylcholine, and leukocyte and platelet adhesion in postcapillary venules of wild-type (WT), immunodeficient (SCID), and IFN-gamma(-/-) mice on a normal (ND) or high-cholesterol (HC) diet. Acetylcholine-induced arteriolar dilation was impaired in WT-HC, compared with WT-ND. This endothelial dysfunction was absent in SCID-HC or IFN-gamma(-/-)-HC mice. Vasodilation was impaired by transfer of WT, but not IFN-gamma(-/-), T-cells to these immunodeficient mice. WT-HC mice exhibited elevated leukocyte and platelet adhesion in venules, versus WT-ND. This blood cell recruitment was attenuated to ND levels in SCID-HC and IFN-gamma(-/-)-HC mice, but restored to WT-HC levels by transfer of WT, but not IFN-gamma(-/-), T-lymphocytes. CONCLUSIONS: These data reveal a novel role of T-lymphocyte-derived IFN-gamma in the development of endothelial dysfunction in arterioles during hypercholesterolemia and extend our previous observations that IFN-gamma mediates both inflammatory and thrombogenic responses to hypercholesterolemia in postcapillary venules.

Role of platelets in hypercholesterolemia-induced leukocyte recruitment and arteriolar dysfunction.

OBJECTIVE: To define the contribution of platelets, specifically platelet-associated P-selectin, to the altered venular and arteriolar responses induced by hypercholesterolemia. METHODS: Leukocyte and platelet recruitment in cremasteric venules, and endothelium-dependent relaxation (EDR) in arterioles were determined using intravital videomicroscopy. Wild-type (WT) mice were placed on a normal or high cholesterol diet. Hypercholesterolemic mice were treated with blocking antibodies against either P-selectin or PSGL-1, or were depleted of neutrophils (ANS) or platelets (APS). Bone marrow chimeras (P-selectin deficiency in platelets, but not in endothelial cells) were produced by transplanting bone marrow from P-selectin-/- into WT mice (P-sel-/---> WT). RESULTS: Hypercholesterolemia (HC) elicited the recruitment of adherent platelets and leukocytes in venules and an impaired EDR in arterioles. The exaggerated cell adhesion responses were absent in hypercholesterolemic mice treated with ANS, anti-P-selectin or anti-PSGL-1 antibodies and in P-sel-/---> WT chimeras. The hypercholesterolemia-induced impairment of arteriolar EDR was significantly blunted in mice rendered either neutropenic or thrombocytopenic, and in P-sel-/---> WT chimeras. CONCLUSIONS: The findings indicate that platelet-associated P-selectin contributes to the recruitment of leukocytes and platelets in venules of hypercholesterolemic mice and that the P-selectin-mediated adhesive interactions also contribute to the impaired arteriolar function induced by hypercholesterolemia.