Comparison of drugs for active eosinophilic oesophagitis: systematic review and network meta-analysis

Background There is currently no recommendation regarding preferred drugs for active eosinophilic oesophagitis (EoE) because their relative efficacy is unclear. We conducted an up-to-date network meta-analysis to compare proton pump inhibitors, off-label and EoE-specific topical steroids, and biologics in EoE. Methods We searched MEDLINE, Embase, Embase Classic and the Cochrane Central Register of Controlled Trials from inception to June 2023. We included randomised controlled trials (RCTs) comparing efficacy of all drugs versus each other, or placebo, in adults and adolescents with active EoE. Results were reported as pooled relative risks with 95% CIs to summarise effect of each comparison tested, with drugs ranked according to P score Results Seventeen RCTs were eligible for systematic review. Of these, 15 studies containing 1813 subjects with EoE reported extractable data for the network meta-analysis. For histological remission defined as ≤6 eosinophils/high-power field (HPF), lirentelimab 1 mg/kg monthly ranked first. For histological remission defined as ≤15 eosinophils/HPF, budesonide orally disintegrating tablet (BOT) 1 mg two times per day ranked first. For failure to achieve symptom improvement, BOT 1 mg two times per day and budesonide oral suspension (BOS) 2 mg two times per day were significantly more efficacious than placebo. For failure to achieve endoscopic improvement based on the EoE Endoscopic Reference Score, BOT 1 mg two times per day and BOS 1 mg two times per day or 2 mg two times per day were significantly more efficacious than placebo. Conclusions Although this network meta-analysis supports the efficacy of most available drugs over placebo for EoE treatment, significant heterogeneity in eligibility criteria and outcome measures among available trials hampers the establishment of a solid therapeutic hierarchy

Antidiabetic Drugs in Alzheimer's Disease: Mechanisms of Action and Future Perspectives

Diabetes mellitus (DM) and Alzheimer’s disease (AD) are two highly prevalent conditions in the elderly population and major public health burden. In the past decades, a pathophysiological link between DM and AD has emerged and central nervous system insulin resistance might play a significant role as a common mechanism; however, other factors such as inflammation and oxidative stress seem to contribute to the shared pathophysiological link. Both preclinical and clinical studies have evaluated the possible neuroprotective mechanisms of different classes of antidiabetic medications in AD, with some promising results. Here, we review the evidence on the mechanisms of action of antidiabetic drugs and their potential use in AD

COPD management as a model for all chronic respiratory conditions : report of the 4th Consensus Conference in Respiratory Medicine

Background: Non-communicable diseases (NCDs) kill 40 million people each year. The management of chronic respiratory NCDs such as chronic obstructive pulmonary disease (COPD) is particularly critical in Italy, where they are widespread and represent a heavy burden on healthcare resources. It is thus important to redefine the role and responsibility of respiratory specialists and their scientific societies, together with that of the whole healthcare system, in order to create a sustainable management of COPD, which could become a model for other chronic respiratory conditions. Methods: These issues were divided into four main topics (Training, Organization, Responsibilities, and Sustainability) and discussed at a Consensus Conference promoted by the Research Center of the Italian Respiratory Society held in Rome, Italy, 3-4 November 2016. Results and conclusions: Regarding training, important inadequacies emerged regarding specialist training - both the duration of practical training courses and teaching about chronic diseases like COPD. A better integration between university and teaching hospitals would improve the quality of specialization. A better organizational integration between hospital and specialists/general practitioners (GPs) in the local community is essential to improve the diagnostic and therapeutic pathways for chronic respiratory patients. Improving the care pathways is the joint responsibility of respiratory specialists, GPs, patients and their caregivers, and the healthcare system. The sustainability of the entire system depends on a better organization of the diagnostic-therapeutic pathways, in which also other stakeholders such as pharmacists and pharmaceutical companies can play an important role

Systematic Review: esophageal motility patterns in patients with eosinophilic esophagitis

Background: Eosinophilic esophagitis (EoE) is a chronic disorder of the esophagus characterized by an eosinophil-predominant inflammation and symptoms of esophageal dysfunction. Eosinophils can influence esophageal motility, leading to dysphagia worsening. The spectrum of esophageal motility in EoE is uncertain. Aim: We performed a systematic review to investigate esophageal motility in EoE. Methods: MEDLINE, EMBASE and EMBASE Classic were searched from inception to 16th November 2021. Studies reporting esophageal motility findings in EoE patients by means of conventional, prolonged, and/or high-resolution esophageal manometry were eligible. Results: Studies on esophageal conventional and high-resolution manometry (HRM) found that all types of manometric motor patterns can be found in patients with EoE and investigations on 24-hour prolonged manometry demonstrated an association between symptoms and intermittent dysmotility events, which can be missed during standard manometric analysis. Panesophageal pressurizations are the most common HRM finding and may help in formulating a clinical suspicion. Some motility abnormalities may reverse after medical treatment, while other major motility disorders like achalasia require invasive management for symptoms control. HRM metrics have demonstrated to correlate with inflammatory and fibrostenotic endoscopic features of EoE. Conclusion: Esophageal motor abnormalities are common in patients with EoE and may contribute to symptoms. The resolution of dysmotility after medical treatment corroborates that eosinophils influence esophageal motility

Systematic review with meta-analysis: artificial intelligence in the diagnosis of oesophageal diseases

Background: Artificial intelligence (AI) has recently been applied to endoscopy and questionnaires for the evaluation of oesophageal diseases (ODs). Aim: We performed a systematic review with meta-analysis to evaluate the performance of AI in the diagnosis of malignant and benign OD. Methods: We searched MEDLINE, EMBASE, EMBASE Classic and the Cochrane Library. A bivariate random-effect model was used to calculate pooled diagnostic efficacy of AI models and endoscopists. The reference tests were histology for neoplasms and the clinical and instrumental diagnosis for gastro-oesophageal reflux disease (GERD). The pooled area under the summary receiver operating characteristic (AUROC), sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR) and diagnostic odds ratio (DOR) were estimated. Results: For the diagnosis of Barrett's neoplasia, AI had AUROC of 0.90, sensitivity 0.89, specificity 0.86, PLR 6.50, NLR 0.13 and DOR 50.53. AI models’ performance was comparable with that of endoscopists (P = 0.35). For the diagnosis of oesophageal squamous cell carcinoma, the AUROC, sensitivity, specificity, PLR, NLR and DOR were 0.97, 0.95, 0.92, 12.65, 0.05 and DOR 258.36, respectively. In this task, AI performed better than endoscopists although without statistically significant differences. In the detection of abnormal intrapapillary capillary loops, the performance of AI was: AUROC 0.98, sensitivity 0.94, specificity 0.94, PLR 14.75, NLR 0.07 and DOR 225.83. For the diagnosis of GERD based on questionnaires, the AUROC, sensitivity, specificity, PLR, NLR and DOR were 0.99, 0.97, 0.97, 38.26, 0.03 and 1159.6, respectively. Conclusions: AI demonstrated high performance in the clinical and endoscopic diagnosis of OD

Modern diagnosis of early esophageal cancer: From blood biomarkers to advanced endoscopy and artificial intelligence

none10noEsophageal cancer (EC) is the seventh most common cancer and the sixth cause of cancer death worldwide. Histologically, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) account for up to 90% and 20% of all ECs, respectively. Clinical symptoms such as dysphagia, odynophagia, and bolus impaction occur late in the natural history of the disease, and the diagnosis is often delayed. The prognosis of ESCC and EAC is poor in advanced stages, being survival rates less than 20% at five years. However, when the diagnosis is achieved early, curative treatment is possible, and survival exceeds 80%. For these reasons, mass screening strategies for EC are highly desirable, and several options are currently under investigation. Blood biomarkers offer an inexpensive, non-invasive screening strategy for cancers, and novel technologies have allowed the identification of candidate markers for EC. The esophagus is easily accessible via endoscopy, and endoscopic imaging represents the gold standard for cancer surveillance. However, lesion recognition during endoscopic procedures is hampered by interobserver variability. To fill this gap, artificial intelligence (AI) has recently been explored and provided encouraging results. In this review, we provide a summary of currently available options to achieve early diagnosis of EC, focusing on blood biomarkers, advanced endoscopy, and AI.noneVisaggi P.; Barberio B.; Ghisa M.; Ribolsi M.; Savarino V.; Fassan M.; Valmasoni M.; Marchi S.; de Bortoli N.; Savarino E.Visaggi, P.; Barberio, B.; Ghisa, M.; Ribolsi, M.; Savarino, V.; Fassan, M.; Valmasoni, M.; Marchi, S.; de Bortoli, N.; Savarino, E

Treatment Trends for Eosinophilic Esophagitis and the Other Eosinophilic Gastrointestinal Diseases: Systematic Review of Clinical Trials

Background Eosinophilic gastrointestinal diseases (EGIDs) are chronic inflammatory disorders of the gut, including eosinophilic esophagitis (EoE), gastritis (EoG), duodenitis (EoD), gastroenteritis (EoGE), and colitis (EoC). Available treatments may be ineffective in some patients, and several clinical trials are investigating alternative treatments. Aim We performed a systematic review of clinical trials to illustrate EGIDs treatment research trends. Methods We searched clinicaltrials.gov to identify studies investigating EGIDs treatment. For each trial we analysed relevant data, including therapeutic intervention, method of administration, study outcomes, and temporal trends. Results For EoE, 66 studies were eligible: 26 testing topical corticosteroids (39.4%), 17 (25.8%) monoclonal antibodies, eight (12.1%) dietary measures, five (7.6%) immunomodulators, one (1.5%) esophageal dilation, and nine (13.6%) other medical treatment strategies. With regard to EoG, EoD, and EoGE, 10 studies were testing monoclonal antibodies (71.5%), one immunomodulators (7.1%), one dietary measures (7.1%), and two other treatments (14.3%). There were no trials for EoC. Ongoing studies on corticosteroids are focused on novel delivery systems, including viscous suspensions, orally disintegrating tablets, or capsules. Increased research on monoclonal antibodies was seen from 2018, with interleukin (IL)-4 receptor-α, IL-5 receptor-α, IL-5, IL-13, IL-15, and Siglec-8 as the targets. Conclusion Clinical trials on EGIDs are predominantly investigating corticosteroids or monoclonal antibodies. EGIDs therapeutic landscape will be trasnformed imminently

Rapid Drink Challenge During High-resolution Manometry for Evaluation of Esophageal Emptying in Treated Achalasia

Background & Aims: Incomplete esophageal emptying is a key variable predicting symptom relapse after achalasia treatment. Although optimally evaluated using the timed barium esophagogram (TBE), incomplete esophageal emptying can also be identified on rapid drink challenge (RDC) performed during high-resolution manometry. Methods: We evaluated if RDC differentiates complete from incomplete esophageal emptying in treated patients with achalasia, against a TBE gold standard. Unselected treated patients with achalasia with both TBE (200 mL of low-density barium suspension) and RDC (200 mL of water in sitting position) were enrolled in 5 tertiary referral centers. TBE barium column height at 1, 2, and 5 minutes were compared with RDC variables: pressurizations >20 mmHg, maximal RDC pressurization, proportion of RDC time occupied by pressurizations, trans-esophagogastric junction gradient, and integrated relaxation pressure. Results: Of 175 patients recruited (mean age, 59 years; 47% female), 138 (79%) were in clinical remission. Complete TBE emptying occurred in 45.1% at 1 minute, 64.0% at 2 minutes, and 73.1% at 5 minutes. RDC integrated relaxation pressure correlated strongly with TBE column height, and a 10-mmHg threshold discriminated complete from incomplete emptying at all 3 TBE time points with area under receiver operating characteristic curves of 0.85, 0.87, and 0.85, respectively. This threshold had high negative predictive values for complete emptying (88% at 2 minutes, 94% at 5 minutes), and modest positive predictive values for incomplete emptying (77% at 2 minutes, 62% at 5 minutes). Conclusions: RDC during high-resolution manometry is an effective surrogate for TBE in assessing esophageal emptying in treated patients with achalasia

Treatment Trends for Eosinophilic Esophagitis and the Other Eosinophilic Gastrointestinal Diseases: Systematic Review of Clinical Trials: Future Treatments for EGIDS: Systematic Review

Background: Eosinophilic gastrointestinal diseases (EGIDs) are chronic inflammatory disorders of the gut, including eosinophilic esophagitis (EoE), gastritis (EoG), duodenitis (EoD), gastroenteritis (EoGE), and colitis (EoC). Available treatments may be ineffective in some patients, and several clinical trials are investigating alternative treatments. Aim: We performed a systematic review of clinical trials to illustrate EGIDs treatment research trends. Methods: We searched clinicaltrials.gov to identify studies investigating EGIDs treatment. For each trial we analysed relevant data, including therapeutic intervention, method of administration, study outcomes, and temporal trends. Results: For EoE, 66 studies were eligible: 26 testing topical corticosteroids (39.4%), 17 (25.8%) monoclonal antibodies, eight (12.1%) dietary measures, five (7.6%) immunomodulators, one (1.5%) esophageal dilation, and nine (13.6%) other medical treatment strategies. With regard to EoG, EoD, and EoGE, 10 studies were testing monoclonal antibodies (71.5%), one immunomodulators (7.1%), one dietary measures (7.1%), and two other treatments (14.3%). There were no trials for EoC. Ongoing studies on corticosteroids are focused on novel delivery systems, including viscous suspensions, orally disintegrating tablets, or capsules. Increased research on monoclonal antibodies was seen from 2018, with interleukin (IL)-4 receptor-α, IL-5 receptor-α, IL-5, IL-13, IL-15, and Siglec-8 as the targets. Conclusion: Clinical trials on EGIDs are predominantly investigating corticosteroids or monoclonal antibodies. EGIDs therapeutic landscape will be trasnformed imminently