Citations

Despite advances in percutaneous coronary procedures, in-stent restenosis remains a significant challenge. Although sirolimus- and paclitaxel-coated balloons are promising alternatives, their comparative safety and efficacy remain uncertain. PubMed, Embase, and Cochrane databases were searched using relevant keywords from inception until August 2025. A total of 11 studies (7 randomized controlled trials and 4 observational cohort studies) were included, comprising 3633 participants overall. The primary outcomes assessed were target lesion revascularization and target lesion failure. Meanwhile, the Secondary outcomes included stent thrombosis, all-cause mortality, myocardial infarction, major adverse cardiovascular events, survival, binary restenosis, and angiographic endpoints (acute gain, diameter stenosis, in-segment late lumen loss, in-lesion late lumen loss, and in-segment minimal lumen diameter). Interstudy heterogeneity was assessed using I ² and X ² statistics ( I ²>50% = significant heterogeneity). Interstudy heterogeneity was low for most outcomes, including all primary clinical endpoints, with moderate heterogeneity observed only for select angiographic measures (notably in-segment late lumen loss and diameter stenosis). Statistical analysis was conducted using R software and RStudio (version 4.4.2), with a P value of < 0.05 indicating statistical significance. This meta-analysis examined studies that compared paclitaxel-coated balloon (PCB) versus standard balloon [sirolimus-coated balloon (SCB)] angioplasty. Regarding primary outcomes, there were no notable variations in target lesion failure [risk ratio (RR), 1.08, 95% CI, 0.90–1.29, P = 0.36] or target lesion revascularization (RR, 1.16, 95% CI, 0.98–1.37, P = 0.08). With all aggregated estimates being nonsignificant, secondary outcomes such as stent thrombosis, all-cause mortality, myocardial infarction, major adverse cardiovascular events, and survival were similar between groups. Angiographic endpoints revealed no discernible variations in late lumen loss (in-lesion and in-segment), acute gain, or diameter stenosis. Nonetheless, the SCB group’s minimal lumen diameter was significantly smaller than that of the PCB group (MD, −0.08 mm, 95% CI, −0.14 to −0.01, P = 0.02). In treating coronary in-stent restenosis, SCB and PCBs show similar overall safety and effectiveness; lesion-specific angiographic variations indicate that customized selection may improve patient outcomes.

Objective Inflammatory bowel disease (IBD) is increasingly recognised in the Middle East, but limited regional data hinder a clear understanding of its burden. We aimed to examine trends in IBD diagnoses, disease phenotypes and predictors of poor outcomes at a major tertiary referral centre in the United Arab Emirates (UAE). Methods In this retrospective observational study, we evaluated diagnostic trends in a cohort of 600 Arab patients between 2002 and June 2025 and analysed detailed phenotypes in a subcohort of 414 patients diagnosed since 2012. Results We observed a nearly 13-fold increase in new IBD diagnoses among Arab patients at our centre between 2002 and 2024. This cohort (median age at diagnosis 25 years; 65% Crohn’s disease (CD; n=269), 35% ulcerative colitis (UC; n=145)) demonstrated a sharper rise in CD compared with UC, with CD being diagnosed at a significantly younger age (median 25 years vs 30 years, p=0.001). A substantial proportion of patients with CD presented with complicated disease defined as stricturing (B2; 22%, n=59), penetrating (B3; 17%, n=46) and perianal (34%, n=92) disease. Ileocolonic (L3) disease was a significant predictor for presenting with a complicated phenotype (OR 3.89). Penetrating (OR 13.9), stricturing (OR 3.38) and perianal (OR 2.22) disease were significant predictors for requiring surgery. 84% of patients with CD and 62% of patients with UC were exposed to advanced therapy. A diagnosis of CD and younger age at diagnosis were associated with a higher likelihood of needing advanced therapy. Conclusions This study provides the most comprehensive data set on IBD diagnoses and phenotypes in the UAE to date, highlighting a pronounced rise in IBD overall and of aggressive disease presentations in CD in particular.

e17089 Background: Prostate cancer (PC) is often treated with androgen-deprivation therapy (ADT), but progression remains a challenge. Darolutamide, a next-generation androgen receptor inhibitor, may improve outcomes when combined with ADT. This systematic review and meta-analysis evaluates the efficacy and safety of darolutamide plus ADT in hormone-sensitive (HSPC) and castration-resistant prostate cancer (CRPC). Methods: A comprehensive search of PubMed, Cochrane, Clinicaltrials.gov, Embase, and Scopus was conducted through January 11, 2025. Randomized controlled trials (RCTs) comparing darolutamide plus ADT vs. placebo or control in prostate cancer were included. Data on overall survival, metastatic progression, antineoplastic therapy initiation, pain progression, bone fractures, hypertension, adverse events and serious adverse events were analyzed. Outcomes were pooled as risk ratios (RR) with 95% confidence intervals (CI) using a random-effects model. Heterogeneity was assessed via Higgins I², with subgroup analyses for HSPC and CRPC. Results: Four RCTs with 4,992 patients (darolutamide + ADT=3007; control=1985) were further included for quantitative analysis. Our pooled analysis showed a statistically significant decrease in the development of metastatic CRPC across both HSPC and CRPC (RR: 0.38 [0.19, 0.77], p=0.007). Similarly, progression to pain (RR: 0.81 [0.71, 0.92], p=0.001) and the use of antineoplastic therapy (RR: 0.46 [0.38, 0.57], p<0.0001) was significantly delayed across all PC, indicating slower disease progression. While a slightly higher overall survival was noted in the CRPC subgroup (RR: 1.08 [1.01, 1.14], p=0.007), no significant differences were reported on the use of combination therapy across HSPC and overall PC (RR: 0.71 [0.39, 1.31], p=0.28). While a significantly higher risk of developing adverse events (RR: 1.08 [1.03, 1.14], p=0.002) and serious adverse events (RR:1.2 [0.99, 1.45], p=0.07) was noted in the CRPC subgroup, a slight increase was reported in the overall cohort and HSPC, although with statistical insignificance. Bone fractures (RR: 1.52 [1.12, 2.07], p=0.008) and hypertension risk (RR: 1.28 [1.03, 1.59], p=0.03) were elevated, while rates of rash, fatigue, falls, and mental impairment were similar. Conclusions: Combination therapy of darolutamide and ADT reduced metastatic progression and slowed tumor growth but did not significantly improve overall survival. Adverse events were more common, particularly in CRPC cohort. Longer follow-up studies are needed to assess long-term efficacy and weigh tumor control against adverse event risks.

Abstract Background The Middle East is experiencing a rapid increase in inflammatory bowel disease (IBD) likely due to urbanization, dietary changes and environmental factors. The region lacks sufficient data, making it challenging to comprehend the full extent of IBD's impact on healthcare systems. This research aims to investigate IBD trends, disease behaviour, evolution and persistence of advanced therapy (AT) within a predominantly Arab patient population in UAE. Methods This observational study at a tertiary IBD centre in the UAE utilized the local IBD registry (prospective data collection from 2022). Data included disease characteristics, and AT usage. Descriptive statistics, regression models and Kaplan-Meier analysis were employed. Results Of the 859 IBD patients treated from 2012 to 2024, comprehensive data were available for 321 patients under active follow-up of which 64.2% comprised of Crohn’s disease (CD) and 35.8% with ulcerative colitis (UC). A ten-fold rise over a 22-year period in new diagnoses of IBD, particularly CD was observed. Median age at diagnosis was 25 years (IQR 25-42), with CD patients younger (24 years) than UC patients (28 years). Within CD, 20% had stricturing, 17% penetrating and 36% with perianal disease. 85% of CD and 61% of UC patients were exposed to at least one AT; 25% of CD and 18% of UC patients &gt;2 ATs, and 16% of CD and 11% of UC &gt;3 ATs. Infliximab and adalimumab were the main first-line ATs, while ustekinumab and risankizumab used in later AT lines. Ustekinumab and risankizumab, showed higher AT persistence compared to anti-TNFs. In CD, stricturing disease (p&lt;0.05), penetrating disease (p&lt;0.01), longer disease duration (p&lt;0.05), and younger age at diagnosis (p&lt;0.05) were linked to higher exposure to AT lines. In UC, younger age at diagnosis (p=0.001) was associated with increased number of AT exposures. Use of AT significantly changed between 2017–2020 and 2021–2024 (p&lt;0.001). Infliximab, adalimumab and vedolizumab were initially the most prevalent, with ustekinumab, risankizumab, and upadacitinib usage rising substantially by 2022. The time to initiate AT for CD and UC following diagnosis decreased significantly since 2017 by 6.82 and 6.91 months per year, respectively (p&lt;0.001), with a combined median time of 2.46 months (IQR 4.8) for CD for 2023-2024. Conclusion This is the first comprehensive evaluation of IBD in the UAE, highlighting a significant rise in new diagnoses, particularly CD with aggressive phenotypes, reflecting broader regional trends. AT utilization has evolved, with ustekinumab and risankizumab demonstrating better persistence and increasing adoption. These insights into disease patterns will help inform future regional healthcare policies.

Background: Diagnosis of gastroesophageal reflux disease (GERD) relies on recognizing symptoms of reflux and mucosal changes during esophagogastroduodenoscopy. The desired response to acid suppression therapy is reliable resolution of GERD symptoms; however, these are not always reliable, hence the need for pH testing in unclear cases. Our objective was to identify potential predictors of a high DeMeester score among patients with potential GERD symptoms to identify patients most likely to have pathological GERD. Methods: We conducted a retrospective case-control study on patients who underwent wireless pH monitoring from January 2020 to April 2022. Cases were patients with a high DeMeester score (more than 14.7), indicating pathological reflux, and controls were those without. We collected clinical and demographic data, including age, sex, body mass index (BMI), smoking status, non-steroidal anti-inflammatory drugs (NSAIDs) use, and presence of atypical symptoms. Results: 86 patients were enrolled in the study. 46 patients with high DeMeester scores were considered cases, and 40 patients with DeMeester scores less than 14.7 were considered controls. Esophagitis (grade A) was found in 41.1% of the cases and in 22.5% of the control group. In our study, age of more than 50 years compared with age of 20-29 years and being overweight appeared to be predictors of true pathological reflux among patients with reflux symptoms who underwent wireless pH monitoring. Conclusion: Age above 50 years compared with age between 20-29 years and being overweight appeared to be predictors of true pathological reflux among patients with reflux symptoms who underwent wireless oesophageal pH monitoring. The presence of oesophagitis was approximately four times more likely to be associated with true pathological reflux.

Abstract Rigosertib, a novel orally bioavailable small molecule inhibitor of PI3-Kinase and PLK1 pathways, was tested in a phase II study in lower risk (intermediate-1 or low risk per IPSS classification) transfusion-dependent MDS patients. This randomized, two-arm study administered rigosertib (560 mg bid) either intermittently (2 out of 3 weeks) or continuously to transfusion-dependent patients (4 units RBC transfusions over 8 weeks). Erythrocyte stimulating agents (ESAs) were allowed on study. Forty eight patients have been enrolled as of August 2nd, 2013 and another 12 patients will be enrolled. Continuous dosing was stopped after 9 patients due to a higher urinary toxicity resulting in 39 patients receiving intermittent dosing. Overall the drug was well tolerated, except for reversible grade 3 urinary toxicity (dysuria, hematuria, cystitis, and urinary urgency) in 6/48 (12%) patients while 17/48 (35%) experienced grade 2 urinary toxicity. Notably, no significant treatment emergent myelosuppression was evident in these patients. Dosing has been modified to a total daily dose of 840 mg (560 mg am/280 mg afternoon) to improve urinary tolerability. Other measures to manage urinary symptoms include hydration, sodium bicarbonate and dose reduction or interruption. Of 33 patients (3 with del5q) on intermittent dosing treated for at least 8 consecutive weeks, 15 (45%) achieved transfusion independence (TI or no RBC transfusion for at least 8 consecutive weeks) lasting 8 to 53+ weeks (median=17 weeks). Intent-to-treat analysis showed 17/48 (35%) patients achieved TI. Twelve of 15 responding patients were refractory to prior treatment with ESAs. Fourteen of 15 responding patients (11 out of 12 ESA refractory) received concomitant ESAs, suggesting an effect of rigosertib on ESA resistance or potential synergy with ESA. These effects are being explored in additional trials now in planning. There was no obvious correlation of response to karyotype or other classifications. We hypothesized that DNA methylation profiles could help explain the differences between responders and non-responders. Pre-therapy bone marrow mononuclear cells from 32 patients (including 4 from the prior Phase I study previously reported in ASH 2011) were analyzed using the Illumina 450K methylation array platform. Seven had complete response or CR (TI + increase in Hb >2Gm/dL), 10 had partial response or PR (TI without Hb increase) and 15 had no response or NR. Supervised hierarchical clustering by methylation intensity demonstrated a distinct profile associated with complete responders. Bisulfite sequencing (which allows quantification of multiple consecutive CpGs in an amplicon) of several differentially methylated loci confirmed the Illumina 450K data. In general, hypermethylation of a group of genes was associated with responders. Functional annotation of the hypo and hypermethylated genes which best distinguished CRs from NRs showed that the genes most affected by methylation were related to regulation of transcription followed by genes involved in cell-cell adhesion, inflammatory response, apoptosis and proliferation. Additional patient samples are being analyzed to confirm these results. In this interim analysis the observed correlation of hematological response to genomic methylation status suggests the possibility of preselecting patients likely to benefit from treatment with rigosertib. Conclusions Intermittent dosing of oral rigosertib is well tolerated and active in producing transfusion independence in lower risk MDS patients. A genomic methylation signature, once confirmed in prospective studies, may allow pre-selection of responders. Disclosures: Raza: Onconova Therapeutics: Research Funding. Al-Kali:Onconova Therapeutics: Research Funding. Tibes:Onconova Therapeutics: Research Funding. Spitzer:Onconova Therapeutics: Research Funding. Wilhelm:Onconova Therapeutics: Employment, Equity Ownership. Mukherjee:Onconova Therapeutics: Research Funding.