Rasha Kaddoura

Background: Classical Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythaemia vera, essential thrombocythaemia, and myelofibrosis, frequently occur in patients with renal, hepatic, cardiovascular, or hematologic comorbidities. These vulnerabilities complicate treatment selection, dose adjustment, and toxicity monitoring. However, patients with advanced kidney disease, dialysis dependence, decompensated cirrhosis, severe cytopenias, or overlapping organ impairment are often underrepresented in prospective trials. Summary: This narrative review presents a practical, organ-adapted framework for selecting MPN therapy in clinically complex patients. We define renal and hepatic impairment, compare commonly used cytoreductive and targeted therapies—including hydroxyurea, busulfan, anagrelide, ruxolitinib, fedratinib, momelotinib, pacritinib, ropeginterferon alfa-2b, and pegylated interferon alfa-2a—and discuss their use in dialysis, decompensated liver disease, cytopenic myelofibrosis, anemia-dominant myelofibrosis, and combined organ vulnerability. The proposed approach prioritizes label-based dose modification when available, cautious dose initiation when evidence is extrapolated, structured early monitoring, and multidisciplinary review for high-risk patients. Key Messages: Management of Philadelphia-negative myeloproliferative neoplasms (MPNs) in organ dysfunction should be individualized according to disease phenotype, treatment goal, organ reserve, hematologic tolerance, frailty, and label-specific safety restrictions. In renal impairment, hydroxyurea and ruxolitinib may remain feasible in selected patients when dose-adjusted and monitored closely, whereas dialysis and severe renal impairment require conservative initiation and multidisciplinary review because direct evidence remains limited. In myelofibrosis, JAK inhibitor choice should be phenotype-adapted: ruxolitinib remains a common standard when blood counts and organ function permit, momelotinib is attractive in anemia-dominant disease, pacritinib is particularly relevant in severe thrombocytopenia, and fedratinib is useful in selected settings but requires thiamine-focused safety management. In hepatic dysfunction or overlapping organ vulnerability, therapy should prioritize safety, reversible contributors, conservative starting strategies, explicit stopping rules, and early reassessment.

Background: Outcomes in chronic myeloid leukemia (CML) remain heterogeneous despite effective BCR::ABL1 tyrosine kinase inhibitors (TKIs). Somatic mutations in epigenetic regulators, particularly additional sex combs-like 1 (ASXL1), have been implicated in adverse prognosis, but their clinical impact in CML has not been systematically defined. Methods: A systematic review was conducted using CINAHL, EMBASE, MEDLINE Ultimate, and PubMed from inception through August 2025. A total of 1339 records were identified; the eligible studies included adult and pediatric patients with chronic and advanced-phase (accelerated or blast) CML. After duplicate removal and screening, 11 studies met the inclusion criteria; these included adult patients only and were included in a qualitative synthesis and meta-analysis. ASXL1 mutation status was assessed using validated molecular methods. The outcomes included the molecular response, cytogenetic response, survival, and treatment resistance. Random-effects models were used to calculate the pooled odds ratios (ORs) with 95% confidence intervals (CIs). Statistical heterogeneity was assessed using the I² statistic. Results: Across the included studies, ASXL1 mutations were detected in approximately 15% of patients. At 12 months, patients with ASXL1 mutations had significantly lower odds of achieving a major molecular response (MMR) compared with ASXL1-wildtype patients (OR 0.29; 95% CI 0.16–0.51; p < 0.0001; I² = 30%). No statistically significant difference was observed in the complete cytogenetic response (CCyR) (OR 0.30; 95% CI 0.02–5.31; p = 0.41; I² = 68%). Compared with patients harboring other non-ASXL1 somatic mutations, an ASXL1 mutation was not associated with a significant difference in MMR (OR 0.49; 95% CI 0.23–1.05; p = 0.067; I² = 0%). Conclusions: ASXL1 mutations may be associated with an inferior molecular response to TKI therapy in CML, supporting their role as an adverse prognostic biomarker. These findings highlight the potential value of incorporating myeloid mutation profiling into future CML risk-stratification strategies.

Cardiovascular disease involves complex molecular, cellular, and physiological derangements that present challenges for traditional diagnostic and therapeutic approaches. Precision medicine is an evolving field that seeks to tailor interventions according to an individual's genetic, molecular, and physiological characteristics. By leveraging advanced omics approaches, including genomics, proteomics, metabolomics, and microbiomics, precision medicine may enable more comprehensive patient phenotyping and support the development of more individualized strategies. The emerging concept of precision cardiac rehabilitation (CR) could provide a more tailored approach to cardiac care by integrating artificial intelligence (AI) with multimodal data, including clinical, imaging, physiological, and omics information. In this context, AI has been explored as a tool to support risk assessment, exercise prescription, and monitoring during CR. However, current evidence remains limited and heterogeneous. Omics-based approaches are primarily confined to research and translational settings, and their role in guiding individualized exercise prescription or clinical decision making in CR remains unestablished. Similarly, while AI shows promise for improving adherence, remote monitoring, and data integration, its effectiveness for optimizing clinical outcomes in CR requires further validation. Overall, precision CR represents a promising but still evolving paradigm. Future progress will depend on well-designed clinical trials, real-world data integration, standardized methodologies, and interdisciplinary collaboration to determine whether these technologies can be safely and effectively integrated into routine clinical practice.

Anemia of chronic disease (ACD), also referred to as anemia of inflammation, is a prevalent and clinically significant complication of chronic infection, autoimmune disease, malignancy, and chronic kidney disease. It is characterized by inflammation‐driven iron sequestration, impaired erythropoietin (EPO) production and signaling, and suppression of effective erythropoiesis. Current therapies (iron supplementation and erythropoiesis‐stimulating agents) often address downstream consequences and may be limited by hepcidin‐driven functional iron deficiency, cytokine‐mediated EPO resistance, and safety concerns in vulnerable populations. This review re‐examines ACD through an integrated framework of hepcidin dysregulation, iron sequestration, and inflammatory inhibition of the EPO axis. We then synthesize emerging evidence that sodium–glucose cotransporter 2 (SGLT2) inhibitors produce sustained increases in hemoglobin/hematocrit beyond transient hemoconcentration across cardiovascular and kidney disease trials, including in non‐diabetic populations. Mechanistic studies suggest a coordinated biologic response that may include reduced hepcidin, improved iron mobilization, physiologic augmentation of endogenous EPO, and attenuation of systemic inflammation—pathways directly relevant to ACD. We critically re‐appraise current ACD paradigms by contrasting downstream “replacement” strategies (iron and ESAs) with pathway‐level approaches (HIF‐PHIs and SGLT2 inhibition), and we outline biomarker‐guided study designs to test whether SGLT2 inhibition may act as an adjunctive physiologic modulator of iron–erythropoietic crosstalk in well‐phenotyped inflammatory anemia cohorts, while emphasizing that current evidence remains hypothesis‐generating rather than practice‐changing.

This systematic review evaluated patient characteristics and outcomes of patients presenting with concomitant spontaneous coronary artery dissection (SCAD) and cardiogenic shock (CS) compared with those without CS. Data from four studies were analyzed. A comprehensive electronic literature search was performed by two authors using PubMed and Embase databases from inspection to February 1^st, 2025. MeSH and broad terms including "Coronary Artery Dissection, Spontaneous" OR "SCAD" OR "Coronary Artery Dissection" were used with and without "Clinical Trials" as a search limit. SCAD patients presenting with CS were less likely to be females (OR=0.64, 95% CI: 0.44; 0.94) and have a history of myocardial infarction (OR=0.71, 95% CI: 0.51; 0.99) but more likely to have heart failure (OR=4.79, 95% CI: 3.30) and renal impairment (OR=2.23, 95% CI: 1.43; 3.50) than those without CS. The presence of CS was associated with longer hospital stay (MD=6.53 days, 95% CI: 5.20; 7.86) and worse in-hospital outcomes including death (OR=39.15, 95% CI: 4.73; 324.25), heart failure (OR=5.32, 95% CI: 2.73; 10.37), and stroke (OR=4.91, 95% CI: 2.44; 9.89). In conclusion, concomitant CS with SCAD was associated with worse outcomes than in the absence of CS.

Background: Outcomes in chronic myeloid leukemia (CML) remain heterogeneous despite effective BCR::ABL1 tyrosine kinase inhibitors (TKIs). Somatic mutations in epigenetic regulators, particularly additional sex combs like 1 (ASXL1), have been implicated in adverse prognosis, but their clinical impact in CML has not been systematically defined. Methods: A systematic review was conducted using CINAHL, EMBASE, MEDLINE Ultimate, and PubMed from inception through August 2025. A total of 1,339 records were identified; after duplicate removal and screening, 11 studies met inclusion criteria and were included in qualitative synthesis and meta-analysis. Eligible studies included adult and pediatric patients with chronic and advanced phase (accelerated or blast) CML with ASXL1 mutation status assessed using validated molecular methods. Outcomes included molecular response, cytogenetic response, survival, and treatment resistance. Random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CI). Statistical heterogeneity was assessed using the I² statistic. Results: Across included studies, ASXL1 mutations were detected in approximately 16% of patients. At 12 months, ASXL1-mutated patients had significantly lower odds of achieving major molecular response (MMR) compared with ASXL1–wildtype patients (OR 0.29; 95% CI 0.16–0.51; p< 0.0001; I²=30%). No statistically significant difference was observed in complete cytogenetic response (CCyR) (OR 0.30; 95% CI 0.02–5.31; p=0.41; I²=68%). Compared with patients harbouring other non-ASXL1 somatic mutations, ASXL1 mutation was not associated with a significant difference in MMR (OR 0.49; 95% CI 0.23–1.05; p=0.067; I²=0%). Conclusions: ASXL1 mutations are associated with inferior molecular response to TKI therapy in CML, supporting their role as an adverse prognostic biomarker. These findings highlight the potential value of incorporating myeloid mutation profiling into future CML risk-stratification strategies.

This systematic review compared the characteristics and clinical outcomes between patients with spontaneous coronary artery dissection (SCAD) and those with Takotsubo Syndrome (TS). A systematic literature search was performed in PubMed, Embase, Cochrane Library, Scopus, Web of Science, and ClinicalTrials.gov from inspection to February 1^st, 2025, then it was updated on February 7^th, 2026. The search strategy used the following key words: "Spontaneous Coronary Artery Dissection" OR "Coronary Artery Dissection" OR "SCAD". Additional search was done by adding "Takotsubo Cardiomyopathy," "Takotsubo Cardiomyopathies," or "Takotsubo Syndrome." Data from six studies were analyzed. Patients with SCAD were significantly younger and exhibited lower rates of comorbidities such as dyslipidemia, hypertension, and diabetes than those with TS. Physical stress as a trigger occurred less frequently in patients with SCAD (odds ratio (OR) 0.37, 95% confidence interval (CI): 0.17; 0.83, P=0.0152; I²=91%), who tend to have higher left ventricular ejection fraction value (MD=14.12, 95% CI: 6.71; 21.62, P=0.0002; I²=100%). While there was no significant difference between the groups in terms of in-hospital death or stroke at follow-up, patients with SCAD had significantly lower risk of death at follow-up (OR=0.07, 95% CI: 0.03; 0.21, P2=0%) than patients with TS. In conclusion, patients with SCAD were younger with less frequent comorbidities, and exhibited better long-term survival outcome than those with TS.

Background/Objectives: Heart failure with reduced ejection fraction (HFrEF) is associated with significant neuropsychological burden, including cognitive impairment and mood disturbances. While sacubitril/valsartan has demonstrated cardiovascular benefits, its effects on cognitive and emotional functioning remain underexplored, particularly in Middle Eastern populations. We aimed to evaluate the impact of sacubitril/valsartan on intellectual capacity, cognitive function and mood in patients with HFrEF using an idiographic study design. Methods: This study was conducted in adult patients with HFrEF selected to take sacubitril/valsartan to improve their clinical status. Participants were assessed at baseline and 3 months after treatment initiation using Al Khoudh Cognitive Test, PHQ-9 and Raven’s Progressive Colored Matrices. Results: Following three months of treatment, participants showed a statistically significant improvement in left ventricular ejection fraction (LVEF) (p = 0.043), depression severity (p = 0.025) and a non-significant trend toward improvement in abstract reasoning scores (p = 0.051). On the other hand, participants did not demonstrate significant improvements in the cognitive subdomains assessed by the Al Khoudh Test. Among these subdomains, the largest improvement was observed with verbal fluency (p = 0.057). Improvements in LVEF were not significantly associated with the changes in mood (p = 0.93), cognitive function (p = 0.34) or verbal fluency (p = 0.46). Conclusions: This study provides preliminary, hypothesis-generating evidence of potential short-term improvement in mood and reasoning scores in HFrEF patients treated with sacubitril/valsartan. Notably, these changes were not attributed to the observed improvements in cardiac function. These findings underscore the need for further investigation into the neurocognitive benefits of sacubitril/valsartan in larger and more diverse populations.

BACKGROUND Observational studies reported characteristics and outcomes of patients with secondary mitral valve regurgitation (MR) who underwent transcatheter edge-to-edge repair of the mitral valve. No study investigated the temporal trend of patient characteristics and outcomes in comparison with the published randomized trials. AIM To investigate the temporal trend in baseline characteristics and outcomes of patients with secondary MR who underwent transcatheter edge-to-edge repair of the mitral valve in the real world compared with those from the published landmark trials. METHODS A comprehensive systematic literature search was conducted using MEDLINE, EMBASE, and CENTRAL databases, and the identified observational studies were divided into two five-year recruitment periods. The first period included 36 studies that enrolled patients between 2008 and 2012, and the second period included 25 studies that recruited patients between 2013 and 2017-2018. Pooled variables of each five-year recruitment period were compared with those of the landmark trials. A random-effects model was used for statistical comparisons. RStudio and RevMan software were used for the analysis. RESULTS Overall, there were no major variations in the findings between the first and the second five-year recruitment periods. EVEREST program vs observational studies: Patients in the EVEREST program were more likely to have non-ischemic MR etiology [odds ratio (OR) = 3.59, 95% confidence interval (CI): 2.92-4.42] and atrial fibrillation (OR = 1.71, 95%CI: 1.42-2.06). They were less likely to receive angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (OR = 0.72, 95%CI: 0.58-0.90) and implantable cardiac device (OR = 0.41, 95%CI: 0.33-0.49) as well as less likely to be symptomatic at hospital presentation without a difference in MR grade ≤ 2+ or mortality at 12-month follow-up. COAPT trial vs observational studies: COAPT patients were more likely to have prior myocardial infarction (OR = 1.62, 95%CI: 1.27-2.06) and renal insufficiency (OR = 2.66, 95%CI: 2.05-3.45). They were more likely to receive beta-blockers (OR = 2.54, 95%CI: 1.68-3.85) and an implanted cardiac device (OR = 2.20, 95%CI: 1.71-2.84). There was no difference in procedure success or mortality. MITRA-FR trial vs observational studies: MITRA-FR patients were less likely to have atrial fibrillation (OR = 0.49, 95%CI: 0.34-0.69) and renal insufficiency (OR = 0.18, 95%CI: 0.11-0.28) but more likely to have a history of myocardial infarction (OR = 1.48, 95%CI: 1.06-2.05) and to receive diuretics (OR = 19.81, 95%CI: 2.75-142.48) and implantable cardiac devices (OR = 1.69, 95%CI: 1.21-2.37). At hospital presentation, they were less likely to be symptomatic (OR = 0.25, 95%CI: 0.18-0.35) without a difference in MR grades 3+ and 4+. There was no difference in terms of MR grade or mortality at 12-month follow-up. CONCLUSION Patients in the landmark studies may have favourable or unfavourable characteristics when compared to those in the observational studies, but this did not translate into different outcomes over time.