Prognostic impact of patients' management based on anatomic/functional phenotype: a study in patients with chronic coronary syndromes.

BACKGROUND: In stable coronary artery disease (CAD), the prognostic interaction between clinical variables and treatment appropriateness based on anatomic/functional phenotype needs to be evaluated. METHODS: 1585 consecutive patients underwent myocardial perfusion scintigraphy and coronary angiography within 90 days. Obstructive CAD (> 70% stenosis) with downstream moderate-to-severe ischemia (> 10%) was considered significant. Coronary revascularization was considered appropriate if all hemodynamically significant lesions were revascularized, while medical therapy only was deemed appropriate in the absence of hemodynamically significant CAD. RESULTS: Obstructive CAD and moderate-to-severe ischemia were documented in 1184 (75%) and 466 (29%) patients, respectively. Over mean follow-up of 4.7 ± 2.5 years, the primary endpoint (cardiac death and non-fatal myocardial infarction) occurred in 132 (8.2%) patients. Of patients with obstructive CAD, 797 (67%) were managed appropriately. Patients' management was inappropriate in 389 patients, because either non-hemodynamically significant lesions were revascularized (50%, including 2 patients with non-obstructive lesions being inappropriately revascularized) or ischemia-causing CAD was left untreated (50%). At multivariate analysis, an inappropriate management (P < .001) was correlated with the primary endpoint, together with previous myocardial infarction (P = .009), lower ejection fraction (P < .001) and higher glucose levels (P < .001). CONCLUSIONS: In stable CAD patients, management based on anatomic/functional phenotyping was correlated with a prognostic advantage at long-term follow-up. Correlation between treatment categories and patients' prognosis. A significantly higher event-rate was observed in patients where hemodynamically significant coronary lesions were left untreated-either because MT was not-adherently chosen or in the case of incomplete revascularization-than in those that were revascularized completely (17.6% vs 5.1%; P < .001). Conversely, the revascularization of non-hemodynamically significant CAD correlated with a higher event-rate than that of similar patients managed medically (13.8% vs 8.3%, P = .04). The event-rate of patients in whom coronary revascularization was performed in the presence of hemodynamically significant CAD ('appropriate revascularization') was similar to those with "No CAD/non-obstructive CAD" (5.1% vs 3.5%; P = NS).

Impact of appropriateness in clinical practice: data from a single-centre nuclear cardiology laboratory.

Aims: To verify the level of appropriateness of referral to our nuclear cardiology laboratory for stress myocardial perfusion imaging (MPI) and explore the correlation between test appropriateness patterns and ischaemia. Methods and results: In 1870 consecutive patients (mean age 73 ± 12 years; 33% female) undergoing MPI, the level of imaging test appropriateness was evaluated according to the 2023 Appropriate Use Criteria (AUC) and the current European Society of Cardiology (ESC) guidelines for the management of chronic coronary syndromes. The evidence of moderate-to-severe ischaemia (i.e. summed difference score >7) was recorded. According to the AUC criteria, the MPI of 1638 (88%), 130 (7%), and 102 (5%) patients could be classified as 'appropriate', 'inappropriate', and 'uncertain', respectively. Similarly, in 1685 (90%) patients, the referral to MPI was adherent to ESC guidelines, while in 185 (10%), it was not. The majority of appropriate MPI tests showed the presence of moderate-to-severe ischaemia (55%), while only a limited number (10%; P < 0.05) of MPI tests with uncertain clinical appropriateness or clearly inappropriate indications did not. In patients managed adherently to ESC guidelines, invasive coronary angiography more frequently showed obstructive coronary artery disease (CAD) (93 vs. 47%, P < 0.001) and led to coronary revascularization (65 vs. 23%, P < 0.001) compared with patients managed non-adherently. Conclusion: In a single-centre, single-national, single-modality population, the current rate of appropriate MPI tests is high. Appropriate referrals are associated with a higher probability of moderate-to-severe ischaemia and better downstream resource utilization than inappropriate ones.

The impact of COVID-19 on elective and urgent digestive endoscopic procedures: a report on a year of pandemic in a gastroenterology centre in Italy.

Introduction: The COVID-19 pandemic (COVID-19) affected digestive endoscopic activity worldwide. Resumption and maintenance of elective endoscopic activity are crucial to containing the impact of COVID-19 on mortality and prognosis of gastrointestinal disorders, primarily cancers. Aim: To assess the impact of COVID-19 during and after the lockdown period on endoscopic activity. Material and methods: The endoscopic activity undertaken during the COVID-19-related lockdown (March 2020-May 2020) and in the post-lockdown period (June 2020-March 2021) was compared with that in the corresponding periods of the year before COVID-19 in a gastroenterology centre in Italy. Results: During the lockdown period, there was a reduction in esophagogastroduodenoscopy (EGD), colonoscopy (CSPY), endoscopic ultrasound (EUS), and endoscopic-retrograde cholangiopancreatography (ERCP) of 75.8%, 74.8%, 60%, and 42%, respectively, compared with the corresponding period of the year before COVID-19. During the post-lockdown period to date, EGD, CSPY, EUS, and ERCP increased as compared to the lockdown period (30.6%, 50.6%, 33.6%, and 65.4%, respectively), but only ERCP showed a full recovery when compared with the corresponding period of the year before COVID-19. Conclusions: Endoscopic activity decreased significantly during the COVID-19 lockdown, and only ERCP had a full recovery in the post-lockdown period. The pandemic-related limitations and the backlog of endoscopic procedures represent important reasons for the increased risk or delayed diagnosis of GI cancers.

Efficacy of hemostatic powders as monotherapy or rescue therapy in gastrointestinal bleeding related to neoplastic or non-neoplastic lesions.

BACKGROUND: Hemostatic powder (HP) in gastrointestinal bleeding (GIB) is mainly used as rescue therapy after failure of conventional hemostatic procedures (CHP). AIM: To define the best field of application and the efficacy of HP as first choice monotherapy or rescue therapy. METHODS: We compared the efficacy of HP monotherapy, HP rescue therapy, and CHP in the management of active GIB due to neoplastic and non-neoplastic lesions. RESULTS: A total of 108 patients, 43 treated with HP as either first choice or rescue therapy and 65 with CHP, were included in the study. The most frequent sources of bleeding were peptic ulcer and malignancy. Immediate hemostasis rates were: HP monotherapy = 100% in peptic ulcer and 100% in malignancy; HP rescue therapy = 93.2% in peptic ulcer and 85.7% in malignancy; CHP = 77.9% in peptic ulcer and 41.7 in malignancy. Definitive hemostasis rates were: HP monotherapy = 50% in peptic ulcer and 45.5% in malignancy; HP rescue therapy = 73.3% in peptic ulcer and 85.7% in malignancy; CHP = 69.1% in peptic ulcer and 33.3% in malignancy. No difference was found in terms of additional intervention between the three groups. CONCLUSIONS: HP is highly effective as monotherapy and rescue therapy in GIB. GIB related to malignancy may be the best field of application of HP, but confirmatory studies are necessary.

Efficacy and tolerability of very low-volume bowel preparation in patients with inflammatory bowel diseases.

OBJECTIVES: An adequate bowel preparation is essential for a quality colonoscopy. Patients with inflammatory bowel disease (IBD) show low compliance with bowel preparation due to the large volume of lavage solution to be ingested, especially if active symptoms are present, and the frequency of having a colonoscopy. We evaluated the efficacy and tolerability of a very low-volume (VLV) polyethylene glycol (PEG)-based solution in patients with IBD. METHODS: A cohort of 103 consecutive patients, 56 with Crohn's disease and 47 with ulcerative colitis, received a 1-L PEG-based bowel preparation divided into two 500-mL doses taken the evening before and the morning of the colonoscopy, each dose followed by at least another 500-mL of clear fluids. Colon cleansing was scored according to the Boston Bowel Preparation Scale (BBPS) and evaluated in relation to influencing variables. RESULTS: Bowel cleansing was adequate (BBPS ≥ 6) in 88 patients (85.4%). The time interval between the end of bowel preparation and the beginning of colonoscopy and the disease activity significantly affected colon cleansing. Most patients declared a complete intake of lavage solution (99%), the willingness to repeat the same bowel preparation in a future colonoscopy (86.4%), and a good taste assessment. CONCLUSION: The VLV PEG-based bowel preparation is effective and well accepted by IBD patients. As minimizing the volume of lavage solution required, the VLV-bowel preparation here tested could be of choice in subjects who perform periodically colonoscopy or in those who do not tolerate a larger amount of liquids.

Clinical care pathway program versus open-access system: a study on appropriateness, quality, and efficiency in the delivery of colonoscopy in the colorectal cancer.

Open-access colonoscopy (OAC), whereby the colonoscopy is performed without a prior office visit with a gastroenterologist, is affected by inappropriateness which leads to overprescription and reduced availability of the procedure in case of alarming symptoms. The clinical care pathway (CCP) is a healthcare management tool promoted by national health systems to organize work-up of various morbidities. Recently, we started a CCP dedicated to colorectal cancer (CRC), including a colonoscopy session for CRC diagnosis and prevention. We aimed to evaluate the appropriateness, the quality, and the efficiency in the delivery of colonoscopy with the open-access system and a CCP program in the CRC. Quality indicators for colonoscopy in subjects in the CCP were compared to referrals by general practitioners (OAC) or by non-gastroenterologist physicians (non-gastroenterologist physician colonoscopy, NGPC). Attendance rate to colonoscopy was greater in the CCP group and NGPC group than in the OAC group (99%, 99%, and 86%, respectively). Waiting time in the CCP group was shorter than in the OAC group (3.88 ± 2.27 vs. 32 ± 22.31 weeks, respectively). Appropriateness of colonoscopy prescription was better in the CCP group than in the OAC group (92 vs. 50%, respectively). OAC is affected by the lack of timeliness and low appropriateness of prescription. A CCP reduces the number of inappropriate colonoscopies, especially for post-polypectomy surveillance, and improves the delivery of colonoscopy in patients requiring a fast-track examination. The high rate of inappropriate OAC suggests that this modality of healthcare should be widely reviewed.

IMPlementing split Regimen OVEr Single dose using a Plan-Do-Study-Act approach (IMPROVES study).

Background and aims A split-dose regimen for colonoscopy is recommended by international guidelines, but its adoption is still suboptimal. Our aim was to assess whether a Plan-Do-Study-Act approach (PDSA), a scientific method promoting quality improvement, would be able to improve adherence to a split-dose regimen, and to identify factors influencing its adoption. Methods This study consisted of three phases: Cycle 1: a cross-sectional assessment of split-dose adherence in consecutive outpatients/inpatients undergoing colonoscopies in 74 Italian centers; Educational intervention: regional meetings with literature review, analysis of Cycle 1 data, and discussion on corrective measures; local diffusion of educational material and tools for improvement; Cycle 2: reassessment of split-dose adherence after spontaneous local interventions. Demographic, clinical, and procedural variables were systematically collected. Multivariate logistic regression was used to identify predictors of split-dose adoption. Results In total, 8213 patients (mean age = 60.29 years (SD = 13.58), men = 54 %, outpatients = 88.4 %) were enrolled between 2013 and 2016 (Cycle 1 = 4189 patients and Cycle 2 = 4024 patients). Split-dose adoption rose from 29.1 % in Cycle 1 to 51.1 % in Cycle 2 ( P  < 0.0001), and being enrolled in Cycle 2 independently predicted split-dose adherence (OR = 2.9; 95 %CI 2.6 - 3.3). The adoption improved in all time slots, including colonoscopies scheduled before 0930. The main corrective measures were: rescheduling of colonoscopies after 0930 (between 0930 and 1130: OR = 2.6; 95 %CI 2.3 - 3.1; after 1130: OR = 7; 95 %CI 5.9 - 8.4); the cleansing regimen communicated by the Endoscopy unit (via form: OR = 1.6; 95 %CI 1.3 - 1.9; via visit: OR = 2.1; 95 %CI 1.7 - 2.5); a decrease in the use of deep sedation (OR = 2; 95 %CI 1.7 - 2.5). Conclusions An educational intervention with observation-driven corrections through a PDSA approach was able to substantially increase the adoption of a split-dose regimen.

Reciprocal Regulation Between Smad7 and Sirt1 in the Gut.

In inflammatory bowel disease (IBD) mucosa, there is over-expression of Smad7, an intracellular inhibitor of the suppressive cytokine transforming growth factor-ß1, due to post-transcriptional mechanisms that enhance Smad7 acetylation status thus preventing ubiquitination-mediated proteosomal degradation of the protein. IBD-related inflammation is also marked by defective expression of Sirt1, a class III NAD+-dependent deacetylase, which promotes ubiquitination-mediated proteosomal degradation of various intracellular proteins and triggers anti-inflammatory signals. The aim of our study was to determine whether, in IBD, there is a reciprocal regulation between Smad7 and Sirt1. Smad7 and Sirt1 were examined in mucosal samples of IBD patients and normal controls by Western blotting and immunohistochemistry, and Sirt1 activity was assessed by a fluorimetric assay. To determine whether Smad7 is regulated by Sirt1, normal or IBD lamina propria mononuclear cells (LPMC) were cultured with either Sirt1 inhibitor (Ex527) or activator (Cay10591), respectively. To determine whether Smad7 controls Sirt1 expression, ex vivo organ cultures of IBD mucosal explants were treated with Smad7 sense or antisense oligonucleotide. Moreover, Sirt1 expression was evaluated in LPMC isolated from Smad7-transgenic mice given dextran sulfate sodium (DSS). Upregulation of Smad7 was seen in both the epithelial and lamina propria compartments of IBD patients and this associated with reduced expression and activity of Sirt1. Activation of Sirt1 in IBD LPMC with Cay10591 reduced acetylation and enhanced ubiquitination-driven proteasomal-mediated degradation of Smad7, while inhibition of Sirt1 activation in normal LPMC with Ex527 increased Smad7 expression. Knockdown of Smad7 in IBD mucosal explants enhanced Sirt1 expression, thus suggesting a negative effect of Smad7 on Sirt1 induction. Consistently, mucosal T cells of Smad7-transgenic mice contained reduced levels of Sirt1, a defect that was amplified by induction of DSS colitis. The data suggest the existence of a reciprocal regulatory mechanism between Smad7 and Sirt1, which could contribute to amplify inflammatory signals in the gut.

Appropriateness of the indication for colonoscopy: is the endoscopist the 'gold standard'?

BACKGROUND: The appropriate selection of patients for colonoscopy is crucial for an efficient use of endoscopy. The role of endoscopist in filtering out inappropriate referrals is largely unknown. METHODS: A multicentre, prospective study was performed in which consecutive patients referred for colonoscopy during a 1-month period were enrolled. Before colonoscopy, the endoscopist assessed appropriateness of the endoscopic referral without directly consulting official guidelines, also collecting clinical and demographic variables. Appropriateness of the indication was eventually assessed by a group of experts based on the American Society for Gastrointestinal Endoscopy guidelines, representing the gold standard. Outcomes of the study were the inappropriateness rate and the main related causes, as well as the concordance rate between the endoscopists and the experts. A multivariate analysis was performed to identify predictors of inappropriateness. RESULTS: One thousand seven hundred ninety-nine patients were enrolled in 20 centres, of which 1489 outpatients were included in the final analysis. According to the American Society for Gastrointestinal Endoscopy guidelines, 432 referrals were inappropriate, corresponding to an inappropriateness rate of 29%. At multivariate analysis, prescription of a repeated colonoscopy (≥2 colonoscopies in the same patient) was strongly associated with the inappropriateness of the indication (odds ratio: 8.8; 95% confidence interval: 6.2, 12.7). Postpolypectomy or post-colorectal cancer surveillance accounted for 77% of the inappropriate control procedures. A 79% concordance rate between endoscopist and expert assessment was found. Among the 317 discordant cases, postpolypectomy or post-colorectal cancer surveillance accounted for 51% of the cases, the endoscopists mistakenly classifying it as appropriate in 55% to 61% of the inappropriate cases. CONCLUSIONS: Inappropriateness in outpatient colonoscopy referrals remains high, surveillance procedures representing the most frequent source of inappropriateness.

Ten and eight-day sequential therapy in comparison to standard triple therapy for eradicating Helicobacter pylori infection: a randomized controlled study on efficacy and tolerability.

BACKGROUND: Sequential therapy (SQT) is effective in the eradication of Helicobacter pylori and could become an alternative to standard triple therapy (STT). AIM: To compare the efficacy and tolerability of SQT, for either 8 or 10 days, with a 7-day STT. METHODS: A total of 270 naive H. pylori-positive patients were randomized to receive: SQT for 8 days (SQT-8, n=90) or 10 days (SQT-10, n=90) including esomeprazole 20 mg twice daily (bid) associated with amoxicillin 1000 mg bid (early 4 and 5 d, respectively), followed by esomeprazole 20 mg bid associated with clarithromycin 500 mg bid plus tinidazole 500 mg bid (last 4 and 5 d, respectively); STT (n=90) including esomeprazole 20 mg bid plus amoxicillin 1000 mg bid and clarithromycin 500 mg bid for 7 days. Tolerability was assessed by scoring the severity of symptoms. RESULTS: Eradication rates after SQT-8 and SQT-10 were higher than that of after STT at both intention-to-treat (83% and 86% vs. 66%, P<0.02) and per-protocol analysis (90% and 88% vs. 75%, P<0.05), whereas no difference was found between the 2 SQTs. CONCLUSIONS: This study shows that SQT, for 8 or 10 days, is well tolerated and highly effective in H. pylori eradication and could represent a valid alternative to STT. Further studies, with more power, on larger populations and from other countries are necessary to validate the present findings.