Aziz, Muhammad

Abstract Background Smoldering multiple myeloma (SMM), an asymptomatic precursor of multiple myeloma (MM), carries a variable risk of progression to MM. There is little consensus on the efficacy or optimal timing of treatment in SMM. We systematically reviewed the landscape of all clinical trials in SMM. We compared the efficacy of treatment regimens studied in SMM to results from these regimens when used in newly diagnosed multiple myeloma (NDMM), to determine whether the data suggest deeper responses in SMM versus NDMM. Methods All prospective interventional clinical trials for SMM, including published studies, meeting abstracts, and unpublished trials listed on ClinicalTrials.gov up to April 1, 2023, were identified. Trial-related variables were captured, including treatment strategy and efficacy results. Relevant clinical endpoints were defined as overall survival (OS) and quality of life. Results Among 45 SMM trials identified, 38 (84.4%) assessed active myeloma drugs, while 7 (15.6%) studied bone-modifying agents alone. Of 18 randomized trials in SMM, only one (5.6%) had a primary endpoint of OS; the most common primary endpoint was progression-free survival (n = 7, 38.9%). Among 32 SMM trials with available results, 9 (28.1%) met their prespecified primary endpoint, of which 5 were single-arm studies. Six treatment regimens were tested in both SMM and NDMM; 5 regimens yielded a lower rate of very good partial response rate or better (≥VGPR) in SMM compared to the corresponding NDMM trial (32% vs 63%, 43% vs 53%, 40% vs 63%, 86% vs 89%, 92% vs 95%, and 94% vs 87%, respectively). Conclusion In this systematic review of all prospective interventional clinical trials in SMM, we found significant variability in trial design, including randomization status, primary endpoints, and types of intervention used. Despite the statistical limitations, comparison of treatment regimens revealed no compelling evidence that the treatment is more effective when introduced early in SMM compared to NDMM.

Abstract Background and study aims Barrett’s esophagus (BE) is a precursor condition to esophageal adenocarcinoma (EAC), resulting in transformation of the squamous epithelium of distal esophagus to columnar-lined epithelium with intestinal metaplasia (IM). Liquid nitrogen spray cryotherapy (LNSC) is a non-contact method of BE eradication and has been used both as primary and salvage therapy. We conducted a systematic review and meta-analysis to assess the safety and efficacy of LNSC. Methods We searched multiple databases from inception through December 2021 to identify studies on use of LNSC for Barrett’s neoplasia. Pooled estimates were calculated using random-effects model and results were expressed in terms of pooled proportions with relevant 95 % confidence intervals (CIs) of complete eradication (CE) of dysplasia(D), high grade dysplasia (HGD) and IM. Results Fourteen studies with 707 patients were included in our final analysis. Overall pooled rates of CE-D, CE-HGD and CE-IM were 80.8 % (CI 77.4–83.8; I2 62), 90.3 % (CI 85.2–93.7; I2 33) and 55.8 % (CI 51.7–59.8; I2 73) with follow up ranging from 4.25 months to 69.7 months. In patients with follow up beyond 24 months, the rates of CE-D and CE-IM were 83.6 % (CI 77.6–88.2; I2 60) and 54.7 % (CI 47.6–61.6; I2 81). Among LNSC naïve patients with prior history of endoscopic resection, the rates were 79.9 % (CI 73.3–85.2; I2 50) and 67.1 % (CI 59.5–73.8; I2 0). Pooled rate of therapeutic failures, defined as lack of response to LNSC therapy, was 23.6 % (CI 19.4–28.3; I2 73). Post LNSC strictures and perforation pooled rates were 4 % and 0.8 %, respectively, which are similar to those previously reported for RFA. Conclusions Our analysis suggests that liquid nitrogen spray cryotherapy is an acceptable treatment for BE in both ablation naïve and experienced patients.

Abstract Background and study aims Proton pump inhibitors (PPI) are effective medical therapy options for gastro-esophageal reflux disease (GERD). However, 20 % to 40 % of patients report symptoms despite taking daily PPI. Transoral incisionless fundoplication (TIF2) and magnetic sphincter augmentation (MSA) are less invasive options for the treatment of refractory GERD and are increasingly gaining popularity. Methods We conducted a comprehensive search of several databases to identify relevant studies. Our primary aim was to compare the efficacy of both interventions reported as improvement in Gastroesophageal Reflux Disease-Health Related Quality of Life (GERD-HRQL) score, overall patient satisfaction, improvement in post-procedure regurgitation, and fraction of patients completely off PPI therapy at follow up. Results Twenty-four studies with 1942 patients were included in the final analysis. Both MSA and TIF2 had comparable technical success and clinical success based on improvement in GERD-HRQL scores i. e. 98.8 % (CI 95.6,99.7) vs 98.5 % (CI 95.7,99.5) and 80.4 % (CI 66,89.6) vs 77.7 % (CI 64.1,87.2), respectively. A significantly greater proportion of patients reported improvement in regurgitation, i. e. 91.1 % (CI 83.8,95.3) vs 73.1 % (CI 62.5,81.7) and were able to completely discontinue PPI therapy with MSA compared to TIF2 i. e. 91.3 % (CI 81.5,96.2) vs 63.8 % (CI 51.6,74.4). Patients’ BMI and presence of a hiatal hernia did not have any effect on procedural outcomes. Conclusion Both procedures performed at par when comparing clinical success in terms of improvement in GERD-HRQL scores. In terms of overall patient satisfaction, post procedure regurgitation and cumulative number of patients off PPI therapy, MSA outperforms TIF2.

Abstract Objectives While anti-tumor necrosis factor alpha (anti-TNFa) therapies for Crohn disease (CD) were initially introduced in 1998 for biologic therapies are often introduced after a minimum of 6 years after diagnosis. The benefit of anti-TNFa early in the course of CD is still controversial, with some studies showing better outcomes but others not. To determine whether earlier introduction of anti-TNFa therapy improves efficacy in clinical trials or clinical series, we aimed to perform a meta-analysis comparing early vs late anti-TNFa use in the management of CD. Methods A comprehensive search of MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus was conducted from each database’s inception to November 3, 2019. We included comparative studies of early vs late use of anti-TNFa therapy in adult patients with CD. Results Eleven studies were included in the analysis, with a total of 2501 patients. Meta-analysis demonstrated that the early use of anti-TNFa was associated with a statistically significant decrease in the need for surgery (relative risk [RR] = 0.43; 95% confidence interval [CI], 0.26–0.69; I2 = 68%) and disease progression (RR = 0.51; 95% CI, 0.35–0.75; I2 = 61%). Early use also showed an increase in early remission (RR = 1.94; 95% CI, 1.54–2.46; I2 = 0%) and clinical response. There was no statistically significant difference in achieving late remission (RR = 1.39; 95% CI, 0.94–2.05; I2 = 65%) or mucosal healing (RR = 1.10; 95% CI, 0.63–1.91; I2 = 0%). Conclusion This systematic review suggests that using anti-TNFa earlier in the treatment of CD (within 3 years) may improve clinical outcomes compared to late administration in terms of achieving early clinical remission, clinical response, disease progression, and the need for surgery.