The economic benefits associated with averting these severe consequences can be substantial. ...when disease activity is closely monitored, treatment adjustments can be tailored to the patient's ...immediate needs curtailing the unnecessary use of medications and healthcare resources. Beyond cost considerations, patient-centered outcomes such as improved quality of life, reduced disease burden, and increased productivity should be included in the overarching societal cost–benefit assessment. For this reason, as also hypothesized in ulcerative colitis, the achievement of an increasingly deep remission that simultaneously includes clinical, endoscopic, and transmural disease activity could be associated with improved disease control and patients' quality of life.
Background
Fecal calprotectin (FC) is a non‐invasive marker of gut inflammation which is frequently used to guide therapeutic decisions in patients with inflammatory bowel diseases (IBD). Each step ...of FC measurement can influence the results, leading to misinterpretations and potentially impacting the management of IBD patients. To date, there is high heterogeneity between FC measurements and no current method is universally accepted as a standard.
Aims
Our aim was to provide clear position statementsabout the pre‐analytical and the analytical phases of FC measurement to homogenize FC levels and to minimize variability and risk of misinterpretation through aninternational consensus.
Materials & Methods
Fourteen physicians with expertise in the field of IBD and FC from 11 countries attended a virtual international consensus meeting on July 17th, 2020. A systematic literature was conducted and the literature evidence was shared and discussedamong the participants. Statements were formulated, discussed, and voted. Statements were considered approved if all participants agreed.
Results
Nine statements were formulated and approved. Based on the available evidence, quantitative tests should be preferred for measuring FC. Furthermore, FC measurement, if possible, should always be performed with the same method and factors influencing FC levels should be taken into account when interpreting the results.
Discussion
FC has an increasingly important role in the management of patients with IBD. However, large multicenter studies should be conducted to define the reproducibility and to confirm the diagnostic accuracy of the available FC tests.
Conclusion
FC concentrations guide clinicians' treatment decisions. Our statements have a relevant impact in daily practice and could be applied in clinical trials to standardize FC measurement.
Key Summary
Summarise the established knowledge on this subject.
‐ FC is a surrogate non‐invasive marker of gut inflammation.
‐ FC is closely correlated with endoscopic and histological activity of disease.
‐ High variability exists between FC measurements.
‐ There is no globally accepted cut‐off of FC.
What are the significant findings of this study?
‐ Stool consistency can influence FC extraction.
‐ Quantitative tests are recommended for FC measurement.
‐ Serial FC measurement in an individual patient should be performed with the same FC test.
‐ Interpretation of FC measurement results should include the evaluation of factors that may influence the test.
Background
Ustekinumab and tofacitinib have recently been approved for the management of moderate to severe ulcerative colitis (UC). However, there is no evidence on how they should be positioned in ...the therapeutic algorithm. The aim of this study was to compare tofacitinib and ustekinumab as third‐line therapies in UC patients in whom anti‐TNF and vedolizumab had failed.
Methods
This was a multicenter retrospective observational study. The primary outcome was disease progression, defined as the need for steroids, therapy escalation, UC‐related hospitalization and/or surgery. Secondary outcomes were clinical remission, normalization of C‐reactive protein, endoscopic remission, treatment withdrawal, and adverse events.
Results
One‐hundred seventeen UC patients were included in the study and followed for a median time of 11.6 months (q1–q3, 5.5–18.7). Overall, 65% of patients were treated with tofacitinib and 35% with ustekinumab. In the entire study cohort, 63 patients (54%) had disease progression during the follow‐up period. Treatment with ustekinumab predicted increased risk of disease progression compared to treatment with tofacitinib in Cox regression analysis (HR: 1.93 95% CI: 1.06–3.50 p = 0.030). Twenty‐eight (68%) patients in the ustekinumab group and 35 (46%) in the tofacitinib group had disease progression over the follow‐up period (log‐rank test, p < 0.054). No significant differences were observed for the secondary outcomes. Six and 22 adverse events occurred in the ustekinumab and tofacitinib groups, respectively (15% vs. 31%, p = 0.11).
Conclusions
Tofacitinib was more efficacious in reducing disease progression than ustekinumab in this cohort of refractory UC patients. However, prospective head‐to‐head clinical trials are needed as to confirm these data.
Background
Fecal incontinence is a disabling condition affecting up to 20% of women.
Objective
We investigated fecal incontinence assessment in both inflammatory bowel disease and non-inflammatory ...bowel disease patients to propose a diagnostic approach for inflammatory bowel disease trials.
Methods
We searched on Pubmed, Embase and Cochrane Library for all studies on adult inflammatory bowel disease and non-inflammatory bowel disease patients reporting data on fecal incontinence assessment from January 2009 to December 2019.
Results
In total, 328 studies were included; 306 studies enrolled non-inflammatory bowel disease patients and 22 studies enrolled inflammatory bowel disease patients. In non-inflammatory bowel disease trials the most used tools were the Wexner score, fecal incontinence quality of life questionnaire, Vaizey score and fecal incontinence severity index (in 187, 91, 62 and 33 studies). Anal manometry was adopted in 41.2% and endoanal ultrasonography in 34.0% of the studies. In 142 studies (46.4%) fecal incontinence evaluation was performed with a single instrument, while in 64 (20.9%) and 100 (32.7%) studies two or more instruments were used. In inflammatory bowel disease studies the Wexner score, Vaizey score and inflammatory bowel disease quality of life questionnaire were the most commonly adopted tools (in five (22.7%), five (22.7%) and four (18.2%) studies). Anal manometry and endoanal ultrasonography were performed in 45.4% and 18.2% of the studies.
Conclusion
Based on prior validation and experience, we propose to use the Wexner score as the first step for fecal incontinence assessment in inflammatory bowel disease trials. Anal manometry and/or endoanal ultrasonography should be taken into account in the case of positive questionnaires.
To date motor subtypes of delirium have been evaluated in single-center studies with a limited examination of the relationship between predisposing factors and motor profile of delirium. We sought to ...report the prevalence and clinical profile of subtypes of delirium in a multicenter study.
This is a point prevalence study nested in the "Delirium Day 2015", which included 108 acute and 12 rehabilitation wards in Italy. Delirium was detected using the 4-AT and motor subtypes were measured with the Delirium Motor Subtype Scale (DMSS). A multinomial logistic regression was used to determine the factors associated with delirium subtypes.
Of 429 patients with delirium, the DMSS was completed in 275 (64%), classifying 21.5% of the patients with hyperactive delirium, 38.5% with hypoactive, 27.3% with mixed and 12.7% with the non-motor subtype. The 4-AT score was higher in the hyperactive subtype, similar in the hypoactive, mixed subtypes, while it was lowest in the non-motor subtype. Dementia was associated with all three delirium motor subtypes (hyperactive, OR 3.3, 95% CI: 1.2-8.7; hypoactive, OR 2.8, 95% CI: 1.2-6.5; mixed OR 2.6, 95% CI: 1.1-6.2). Atypical antipsychotics were associated with hypoactive delirium (OR 0.23, 95% CI: 0.1-0.7), while intravenous lines were associated with mixed delirium (OR 2.9, 95% CI: 1.2-6.9).
The study shows that hypoactive delirium is the most common subtype among hospitalized older patients. Specific clinical features were associated with different delirium subtypes. The use of standardized instruments can help to characterize the phenomenology of different motor subtypes of delirium.
Sodium-glucose transporter 2 inhibitors (SGLT2-I) could modulate atherosclerotic plaque progression, via down-regulation of inflammatory burden, and lead to reduction of major adverse cardiovascular ...events (MACEs) in type 2 diabetes mellitus (T2DM) patients with ischemic heart disease (IHD). T2DM patients with multivessel non-obstructive coronary stenosis (Mv-NOCS) have over-inflammation and over-lipids' plaque accumulation. This could reduce fibrous cap thickness (FCT), favoring plaque rupture and MACEs. Despite this, there is not conclusive data about the effects of SGLT2-I on atherosclerotic plaque phenotype and MACEs in Mv-NOCS patients with T2DM. Thus, in the current study, we evaluated SGLT2-I effects on Mv-NOCS patients with T2DM in terms of FCT increase, reduction of systemic and coronary plaque inflammation, and MACEs at 1 year of follow-up.
In a multi-center study, we evaluated 369 T2DM patients with Mv-NOCS divided in 258 (69.9%) patients that did not receive the SGLT2-I therapy (Non-SGLT2-I users), and 111 (30.1%) patients that were treated with SGLT2-I therapy (SGLT2-I users) after percutaneous coronary intervention (PCI) and optical coherence tomography (OCT) evaluation. As the primary study endpoint, we evaluated the effects of SGLT2-I on FCT changes at 1 year of follow-up. As secondary endpoints, we evaluated at baseline and at 12 months follow-up the inflammatory systemic and plaque burden and rate of MACEs, and predictors of MACE through multivariable analysis.
At 6 and 12 months of follow-up, SGLT2-I users vs. Non-SGLT2-I users showed lower body mass index (BMI), glycemia, glycated hemoglobin, B-type natriuretic peptide, and inflammatory cells/molecules values (p < 0.05). SGLT2-I users vs. Non-SGLT2-I users, as evaluated by OCT, evidenced the highest values of minimum FCT, and lowest values of lipid arc degree and macrophage grade (p < 0.05). At the follow-up end, SGLT2-I users vs. Non-SGLT2-I users had a lower rate of MACEs n 12 (10.8%) vs. n 57 (22.1%); p < 0.05. Finally, Hb1Ac values (1.930, CI 95%: 1.149-2.176), macrophage grade (1.188, CI 95%: 1.073-1.315), and SGLT2-I therapy (0.342, CI 95%: 0.180-0.651) were independent predictors of MACEs at 1 year of follow-up.
SGLT2-I therapy may reduce about 65% the risk to have MACEs at 1 year of follow-up, via ameliorative effects on glucose homeostasis, and by the reduction of systemic inflammatory burden, and local effects on the atherosclerotic plaque inflammation, lipids' deposit, and FCT in Mv-NOCS patients with T2DM.
To evaluate atrial fibrillation (AF) recurrence and Sarcoplasmic Endoplasmic Reticulum Calcium ATPase (SERCA) levels in patients treated by epicardial thoracoscopic ablation for persistent AF.
...Reduced levels of SERCA have been reported in the peripheral blood cells of patients with AF. We hypothesize that SERCA levels can predict the response to epicardial ablation.
We designed a prospective, multicenter, observational study to recruit, from October 2014 to June 2016, patients with persistent AF receiving an epicardial thoracoscopic pulmonary vein isolation.
We enrolled 27 patients. Responders (n = 15) did not present AF recurrence after epicardial ablation at one-year follow-up; these patients displayed a marked remodeling of the left atrium, with a significant reduction of inflammatory cytokines, B type natriuretic peptide (BNP), and increased levels of SERCA compared to baseline and to nonresponders (p < 0.05). Furthermore, mean AF duration (Heart rate (HR) 1.235 (1.037-1.471), p < 0.05), Left atrium volume (LAV) (HR 1.755 (1.126-2.738), p < 0.05), BNP (HR 1.945 (1.895-1.999), p < 0.05), and SERCA (HR 1.763 (1.167-2.663), p < 0.05) were predictive of AF recurrence.
Our data indicate for the first time that baseline values of SERCA in patients with persistent AF might be predictive of failure to epicardial ablative approach. Intriguingly, epicardial ablation was associated with increased levels of SERCA in responders. Therefore, SERCA might be an innovative therapeutic target to improve the response to epicardial ablative treatments.
We have reviewed the impact of the ubiquitin proteasome system (UPS) on atherosclerosis progression of diabetic patients. A puzzle of many pieces of evidence suggests that UPS, in addition to its ...role in the removal of damaged proteins, is involved in a number of biological processes including inflammation, proliferation and apoptosis, all of which constitute important characteristics of atherosclerosis. From what can be gathered from the very few studies on the UPS in diabetic cardiovascular diseases published so far, the system seems to be functionally active to a different extent in the initiation, progression, and complication stage of atherosclerosis in the diabetic people. Further evidence for this theory, however, has to be given, for instance by specifically targeted antagonism of the UPS. Nonetheless, this hypothesis may help us understand why diverse therapeutic interventions, which have in common the ability to reduce ubiquitin-proteasome activity, can impede or delay the onset of diabetes and cardiovascular diseases (CVD). People with type 2 diabetes are disproportionately affected by CVD, compared with those without diabetes 1. The prevalence, incidence, and mortality from all forms of CVD (myocardial infarction, cerebro-vascular disease and congestive heart failure) are strikingly increased in persons with diabetes compared with those withoutdiabetes 2. Furthermore, diabetic patients have not benefited by the advances in the management of obesity, dyslipidemia, and hypertension that have resulted in a decrease in mortality for coronary heart disease (CHD) patients without diabetes 3. Nevertheless, these risk factors do not fully explain the excess risk for CHD associated with diabetes 45. Thus, the determinants of progression of atherosclerosis in persons with diabetes must be elucidated. Beyond the major risk factors, several studies have demonstrated that such factors, strictly related to diabetes, as insulin-resistance, post-prandial hyperglycemia and chronic hyperglycemia play a role in the atherosclerotic process and may require intervention 67. Moreover, it is important to recognize that these risk factors frequently "cluster" inindividual patients and possibly interact with each other, favouring the atherosclerosis progression toward plaque instability. Thus, a fundamental question is, "which is the common soil hypothesis that may unifying the burden of all these factors on atherosclerosis of diabetic patients? Because evidences suggest that insulin-resistance, diabetes and CHD share in common a deregulation of ubiquitin-proteasome system (UPS), the major pathway for nonlysosomal intracellular protein degradation in eucaryotic cells 89, in this review ubiquitin-proteasome deregulation is proposed as the common persistent pathogenic factor mediating the initial stage of the atherosclerosis as well as the progression to complicated plaque in diabetic patients.
Abstract Incidence, predictors and impact on prognosis of target lesion revascularization (TLR) for patients treated with second generation drug eluting stents (DESs) on unprotected left main (ULM) ...remain to be defined. The present is a multicenter study including patients treated with a second generation DES on ULM from June 2007 to January 2015. Rate of target lesion revascularization was the primary end point. All cause death, myocardial infarction, target vessel revascularization and stent thrombosis were the secondary end points. 1270 patients were enrolled: after a follow up of 650 days (230-1170) 47 (3.7%) of them underwent a re-PCI TLR on the left main, 22 during a planned angiographic follow up. Extent of CAD was similar among groups (median value of Syntax of 27±10 vs. 26±9, p 0.45), as localization of the lesion in the ULM. Of patients reporting with TLR on ULM; 56% presented with a focal re-stenosis, 33% diffuse and 10% proliferative. At multivariate analysis), insulin dependent diabetes mellitus increased risk of TLR (HR 2.0: 1.1-3.6, p 0.04), while use of IVUS resulted protective (HR 0.5: 0.3-0.9, p 0.02) At follow up, rates of cardiovascular death did not differ among the two groups (4% vs.4%, p 0.95). At multivariate analysis, TLR on LM did not increase risk of all cause death (HR 0.4: 0.1-1.6, p 0.22), while cardiogenic shock and III tertile of Syntax portended a worse prognosis (respectively HR 4.5: 2.1-10.2 p 0.01 and HR 1.4:1.1-1.6 p 0.03).. In conclusion, repeated revascularization after implantation of second generation DES on ULM represents an unfrequent event, being increased in insulin dependent patients and reduced by IVUS. Impact on prognosis remains neutral, being related to clinical presentation and extent of CAD.
PDF
