Complete Endoscopic Healing Is Associated With Lower Relapse Risk After Anti-TNF Withdrawal in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Discontinuation of anti-tumor necrosis factor-α treatment (anti-TNF) (infliximab and adalimumab) in patients with inflammatory bowel disease (IBD) is associated with a high relapse risk that may be influenced by endoscopic activity at the time of stopping. We assessed the relapse rate after anti-TNF withdrawal in patients with endoscopic healing and studied predictors of relapse including the depth of endoscopic healing. METHODS: This was a multicenter, prospective study in adult patients with Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU), with ≥6 months of corticosteroid-free clinical remission (confirmed at baseline) and endoscopic healing (Mayo <2/SES-CD <5 without large ulcers), who discontinued anti-TNF between 2018 and 2020 in the Netherlands. We performed Kaplan-Meier and Cox regression analyses to assess the relapse rate and evaluate potential predictors: partial (Mayo 1/SES-CD 3-4) versus complete (Mayo 0/SES-CD 0-2) endoscopic healing, anti-TNF trough levels, and immunomodulator and/or mesalamine use. RESULTS: Among 81 patients (CD: n = 41, 51%) with a median follow-up of 2.0 years (interquartile range, 1.6-2.1), 40 patients (49%) relapsed. Relapse rates in CD and UC/IBDU patients were comparable. At 12 months, 70% versus 35% of patients with partial versus complete endoscopic healing relapsed, respectively (adjusted hazard rate [aHR], 3.28; 95% confidence interval [CI], 1.43-7.50). Mesalamine use was associated with fewer relapses in UC/IBDU patients (aHR, 0.08; 95% CI, 0.01-0.67). Thirty patients restarted anti-TNF, and clinical remission was regained in 73% at 3 months. CONCLUSIONS: The relapse risk was high after anti-TNF withdrawal in IBD patients with endoscopic healing, but remission was regained in most cases after anti-TNF reintroduction. Complete endoscopic healing and mesalamine treatment in UC/IBDU patients decreased the risk of relapse.

Comparison of primary percutaneous coronary intervention and streptokinase for acute isolated inferior ST elevation myocardial infarction with a predicted low risk profile.

BACKGROUND: Primary percutaneous coronary intervention (PCI) is the treatment of choice for acute myocardial infarction, especially for high-risk patients, but the data for low-risk patients are conflicting. A very low-risk subgroup of acute inferior myocardial infarction can be identified by electrocardiographic and clinical criteria during admission. We aimed to compare the outcomes of primary PCI and streptokinase treatment in this subgroup, which has not been evaluated separately before. MATERIAL/METHODS: We retrospectively analyzed in-hospital and 10-month follow-up outcomes of 97 patients with inferior acute myocardial infarction and clinical and electrocardiographic criteria predicting low risk who have been treated with primary PCI or streptokinase. RESULTS: Forty-eight patients received streptokinase, and 49 had undergone primary PCI. Both during the in-hospital period and follow-up, the groups did not differ in the end points of death, reinfarction, or stroke (in-hospital: 2.1% versus 4.1%, P=.57; follow-up: 8.9% versus 8.9%, P=1.000). Length of hospital stay was longer in the streptokinase group (6.5+/-2.5 versus 9.1+/-3.7 days, P=.001). Rate of repeat revascularization was reduced in the PCI group at 10 months (28.9% versus 55.6%, P=.002). CONCLUSIONS: When streptokinase and primary PCI are compared in isolated inferior acute myocardial infarction patients with a low-risk profile, there are no differences for in-hospital and long-term rates of death, reinfarction, or stroke. Primary angioplasty reduces the length of initial hospital stay, and reduces repeat admissions by decreasing the need for subsequent revascularization procedures. Large-scale studies are needed to reach a final conclusion.

[Coronary artery ectasia: clinical and angiographical evaluation]. / Koroner arter ektazisi: klinik ve anjiyografik degerlendirme.

OBJECTIVES: We investigated the prevalence, distribution, risk factors, and prognosis of coronary artery ectasia (CAE) in patients undergoing coronary angiography for suspected coronary artery disease (CAD). STUDY DESIGN: Of 4,119 patients undergoing elective coronary angiography between 2003 and 2005, 173 patients (139 males, 34 females; mean age 61+/-11 years) had CAE, with a prevalence of 4.2%. Distribution of CAE was made according to the classification of Markis et al. The results were compared with those of 145 control patients (115 males, 30 males; mean age 61+/-10 years) who had CAD but not CAE. Following coronary angiography, treatment was designed as aortocoronary bypass (n=3), percutaneous coronary intervention (n=36), and medical therapy (n=98). The mean follow-up was 34.2+/-2.5 months. RESULTS: Among CAE patients, there was a marked male preponderance with 80.3%. Coronary ectasia was isolated in 46 patients (26.6%) and was associated with significant coronary artery stenoses in 127 patients (73.4%). The only significant difference with the control group with respect to baseline features was the higher frequency of hypertension in the CAE group (p=0.002). Coronary ectasia involved a single vessel in 67.1%, two vessels in 24.9%, and three vessels in 8.1%, with the right coronary artery being the most common localization (50.9%). The diameters of ectatic coronary arteries ranged from 3.2 mm to 9.7 mm (mean 5.6 mm). According to the classification of Markis et al., the majority of patients (64.2%) had type IV ectasia. In multiple regression analysis, hypertension was independently associated with CAE (OR: 0.378; 95% CI: 0.211-0.678; p=0.001). Mortality occurred in nine patients (5.2%). The annual mortality rates were 1.5%, 2.1%, and 2.9% with medical therapy, percutaneous coronary intervention, and aortocoronary bypass, respectively. CONCLUSION: Our findings suggest that further prospective studies focus on the dependent relationship between hypertension and CAE, and on marked coexistence of CAD and CAE.

Level of Selvester QRS score is predictive of ST-segment resolution and 30-day outcomes in patients with acute myocardial infarction undergoing primary coronary intervention.

BACKGROUND: The presence of Q waves at presentation with a first acute ST-segment elevation myocardial infarction (STEMI) reflects a more advanced stage of the infarction. Resolution of ST-segment elevation indicating successful myocyte reperfusion may differ according to how far the infarction process has progressed. The Selvester QRS score measures infarct size. The purpose of this study was to evaluate the predictive value of QRS score on ST-segment resolution and 30-day clinical outcomes in patients with acute STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS: We conducted a prospective cohort study in 112 consecutive patients (mean age 57 +/- 11 years, 94 men, 18 women) with first acute STEMI of <12-hour onset who underwent successful (TIMI-3 flow) primary PCI. The Selvester QRS score was estimated on the first electrocardiogram (ECG) after hospital admission. Sum of ST-segment elevation amount in millimeters was obtained immediately before angioplasty and 60 minutes after the restoration of TIMI-3 flow. The difference between 2 measurements was accepted as the amount of ST-segment resolution and expressed as summation sigmaSTR. summation sigmaSTR <50% was accepted as ECG sign of no-reflow phenomenon. Follow-up to 30-day was performed. RESULTS: The no-reflow phenomenon was more often observed in patients with high QRS score (> or = 4) than in those with low QRS score (34.4% and 6.3%, P < .001). Thirty-day composite major adverse cardiac event (MACE) rate was 14% in patients with high QRS score versus 0% in low QRS score group (P = .007). After adjusting for baseline characteristics, high QRS score remained a strong independent predictor of no-reflow (OR 4.1, 95% CI 1.5-10.7, P = .005) and MACE (OR 1.8, 95% CI 1.1-2.9, P = .011). CONCLUSIONS: The presence of high QRS score is an independent predictor of incomplete ST recovery and 30-day MACE in STEMI treated with primary PCI.

Plasma soluble adhesion molecule levels in coronary artery ectasia.

BACKGROUND: Coronary artery ectasia (CAE) is defined as localized or diffuse dilatation of the coronary arteries. There are scarce data about the role of inflammation in CAE. In the present study, the plasma soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) levels in CAE were investigated. METHODS: The study population (n = 67) consisted of four groups. Group 1: patients with normal coronary artery (NCA); group 2: patients with isolated ectasia without stenotic lesion; group 3: patients with obstructive coronary artery disease (OCAD) without CAE; group 4: patients with both OCAD and CAE. RESULTS: Plasma concentrations of ICAM-1 and VCAM-1 were higher in patients with isolated ectasia than in cases with NCA (p < 0.001 and p < 0.001, respectively). Compared with OCAD patients, patients with CAE had significantly elevated concentrations of ICAM-1 and VCAM-1 (p < 0.001 and p < 0.05, respectively). The levels of ICAM-1 and VCAM-1 of the CAE and OCAD group were higher than in patients in the OCAD group (p < 0.05 and p < 0.05, respectively). We detected a positive correlation between the presence of CAE and the levels of ICAM-1 and VCAM-1. Multivariate logistic regression analyses revealed a significant independent relation between the presence of CAE and ICAM-1 and VCAM-1. CONCLUSION: We found elevated plasma levels of ICAM-1 and VCAM-1 in patients with CAE and OCAD + CAE compared with subjects with NCA and OCAD. These data strongly suggest that more severe vascular wall inflammation may play a role in the pathogenesis of CAE.

Effect of tirofiban therapy on ST segment resolution and clinical outcomes in patients with ST segment elevated acute myocardial infarction undergoing primary angioplasty.

BACKGROUND: In our study, we assessed the effect of glycoprotein (GP) IIb/IIIa receptor inhibition on microvascular flow after acute coronary occlusion using the early sum of ST segment resolution in electrocardiography. Platelets may play a major role in the dissociation of epicardial artery recanalization and tissue level reperfusion, referred to as the 'no-reflow phenomenon'. Therefore, GP IIb/IIIa receptor inhibition might improve myocardial reperfusion, distinct from its effects on epicardial patency. METHODS AND RESULTS: One hundred and fifteen patients (mean age 57.7 +/- 12.2 years, 96 males, 19 females) with < or = 12-hour acute ST segment elevation myocardial infarction who underwent successful primary percutaneous coronary intervention were retrospectively enrolled into the study. Patients were grouped according to whether they received tirofiban therapy or not. Clinical and electrocardiographic parameters were evaluated. The first sum of ST segment elevation amounts in millimeters was obtained immediately before angioplasty and the second 60 min after restoration of thrombolysis in myocardial infarction III flow. The difference between the two measurements was accepted as resolution of the sum of ST segment elevation and expressed as SigmaSTR. There were no significant differences between the groups regarding age, gender, cardiovascular risk factors, and laboratory parameters, duration from angina onset to the emergency unit, and from door to angioplasty. SigmaSTR was higher in patients who received tirofiban than in those who did not (7.2 +/- 2.8 and 4.2 +/- 2.6 mm, respectively; p < 0.001). There was a significant and positive correlation between GP IIb/IIIa inhibition and SigmaSTR (r = 0.336, p < 0.001), as well as between ejection fraction and SigmaSTR (r = 0.310, p < 0.001). GP IIb/IIIa inhibition was the only independent determinant of SigmaSTR in a multivariate linear regression model which contains 10 variables (p < 0.001). The incidence of in-hospital post-myocardial infarction refractory angina, reinfarction, and heart failure was significantly lower in the tirofiban group (p < 0.05, p < 0.05, and p < 0.05, respectively). Additionally, after 30 days, reinfarction and heart failure were lower in the tirofiban group (p < 0.05 and p < 0.05, respectively). CONCLUSIONS: It is well known that SigmaSTR determines microvascular perfusion. This study shows that GP IIb/IIIa inhibition with tirofiban is of value in preserving microvascular perfusion after restoring coronary thrombolysis in myocardial infarction III flow.

Macrophage colony stimulating factor promotes phagocytosis by murine microglia.

Macrophage colony stimulating factor (M-CSF) and its receptor are upregulated in the brain in Alzheimer's disease. M-CSF induces activation and proliferation of microglial cells and expression of proinflammatory cytokines. Amyloid beta (Abeta) immunization experiments suggest that microglia have the capacity to aggressively clear Abeta from the brain under certain circumstances. We examined the role of M-CSF in phagocytosis of fluorescent microspheres and Abeta by cultured microglia. M-CSF treatment increased microglial cell phagocytosis of both microspheres and of Abeta. Antibody neutralization of M-CSF inhibited Abeta uptake induced by overexpression of the M-CSF receptor on microglia. These results suggest that M-CSF could be important in promoting microglial clearance of abnormal protein aggregates such as Abeta.

Macrophage colony stimulating factor prevents NMDA-induced neuronal death in hippocampal organotypic cultures.

Macrophage colony stimulating factor (M-CSF) and its receptor are up-regulated in the brain in Alzheimer's disease (AD), in transgenic mouse models for AD, and experimental models for traumatic and ischemic brain injury. M-CSF induces activation and proliferation of microglial cells and expression of proinflammatory cytokines. We examined the role of M-CSF in excitotoxic neuronal cell death in organotypic hippocampal cultures. NMDA treatment induced neuronal apoptosis and caspase-3 activation in organotypic hippocampal cultures, whereas treatment with M-CSF protected hippocampal neurons from NMDA-induced apoptosis. Caspase-3 activation was inhibited by M-CSF treatment to the same degree as with the caspase inhibitor Z-VAD-FMK. These results suggest that M-CSF has neuroprotective properties through inhibition of caspase-3 that could promote neuronal survival after excitotoxic insult. The role of M-CSF in neurological disease should be reevaluated as a microglial activator with potentially neuroprotective effects.