Mostafa Hossam El Din Moawad

Background: This study examines the clinical efficacy of daratumumab when combined with other therapeutic agents in patients with multiple myeloma, with a focus on key outcomes including overall response, progression-free survival (PFS), and stringent complete response (sCR). Methods: A systematic literature search was conducted using PubMed, Web of Science, Scopus, and the Cochrane Library. Statistical analyses were performed with R software (version 4.2.2). Between-study heterogeneity was assessed using the Cochrane Q test and the I² statistic, while potential publication bias was evaluated through Egger’s regression test and visual inspection of funnel plots. Results: The meta-analysis revealed that daratumumab-containing regimens were associated with a 54.4% reduction in the risk of disease progression or death (hazard ratio[HR] 0.4558; 95% confidence-interval [CI]: 0.4031–0.5154). Similar results were observed using a random-effects model (HR 0.4667; 95% CI: 0.3771–0.5776), despite moderate heterogeneity (I² = 66.7%). Moreover, patients treated with daratumumab were approximately 2.4 times more likely to achieve a stringent complete response (odds-ratio[OR] 2.38; 95% CI: 1.80–3.15), with moderate heterogeneity across studies (I² = 58.2%). Conclusions: Incorporating daratumumab into standard therapy for multiple myeloma significantly enhances progression-free survival and the rate of stringent complete response. Despite some heterogeneity, the consistent positive outcomes support its use as an effective treatment option in clinical practice.

Lung cancer is the most prevalent cancer and cause of death; most patients present themselves at an advanced stage and continuously acquire resistance to targeted agents, antibody–drug conjugates, chemotherapy, and immune checkpoint inhibitors. In addition to secondary mutations, epigenetically driven cellular plasticity, including DNA methylation, histone modification, chromatin remodeling, RNA (m 6A)-marks, and non-coding RNAs, facilitates resistance coordination, EMT/drug-tolerant persisters, lineage switching (e.g., NSCLC to NSCLC), bypass signaling, and immune evasion by tumor cells. These states can be therapeutically rewired by epigenetic drugs: low-dose DNMT/HDAC priming restores silenced tumor-suppressor and antigen-presentation genes and activates viral-mimicry interferon signaling to augment checkpoint blockade; EZH2 and LSD1 inhibitors target plasticity and neuroendocrine programs; BET inhibition suppresses adaptive transcription; CBP/p300 modulators suppress NRF2-dependent redox survival; Combination therapies exploiting synthetic lethality through PRMT5 inhibition, applied rationally with TKIs, ICIs, chemotherapy, and antibody–drug conjugates (ADCs), are currently under clinical investigation. Biomarker-directed patient selection (e.g., MTAP loss clustering, EZH2/LSD1 activity, methylation and chromatin signatures, and liquid biopsy dynamics of methylation or ctDNA) will be critical to enrich for patients most likely to benefit. In the future, better optimized sequencing using short priming windows, intermittent dosing, and future readouts of prospective pharmacodynamics could transform transient re-sensitization into lasting control. This study aims to critically appraise mechanistic and clinical evidence linking epigenetic plasticity to therapy resistance in advanced lung cancer and to propose biomarker-directed epigenetic combination and sequencing strategies to restore drug sensitivity.

Background: The optimal choice of antiplatelet monotherapy after dual antiplatelet therapy (DAPT) among patients undergoing PCI remains debatable. While aspirin has long been the default choice, clopidogrel has emerged as a potential alternative due to its lower bleeding risk and possible superior ischemic protection. This meta-analysis sought to investigate the recent findings comparing the use of aspirin against clopidogrel after different durations of DAPT in patients who underwent PCI. Methods: We searched for randomized controlled trials and cohort studies comparing long-term aspirin and clopidogrel monotherapy after DAPT post-PCI. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included major and minor bleeding, gastrointestinal (GI) bleeding, stroke, myocardial infarction (MI), target vessel revascularization, and stent thrombosis. Results: Six studies comprising 14,992 patients were included. Clopidogrel monotherapy was associated with a significantly lower risk of MACE than aspirin (risk ratio [RR]: 1.24; 95% CI: 1.09–1.42; P = .001). Aspirin monotherapy resulted in a higher risk of minor bleeding (RR: 1.57; 95% CI: 1.06–2.34; P = .03) and GI bleeding (RR: 1.19; 95% CI: 1.04–1.37; P = .01). However, aspirin monotherapy was associated with a higher risk of stroke, including both ischemic (RR: 1.56; 95% CI: 1.03–2.38; P = .04) and hemorrhagic stroke (RR: 2.06; 95% CI: 1.06–3.98; P = .03). Conclusion: Clopidogrel monotherapy appears to be a superior alternative to aspirin for long-term secondary prevention after PCI, offering a lower risk of MACE and stroke without increasing major bleeding or mortality. However, individual factors such as genetic variability, GI bleeding risk, and cost should guide therapy selection.

Phenobarbital (PB) has long been considered the standard first-line therapy for neonatal seizures, despite suboptimal efficacy and concerns about neurotoxi

Background Intravenous thrombolysis remains a cornerstone in acute ischemic stroke (AIS) management, particularly in large vessel occlusion (LVO). While alteplase has long been the standard thrombolytic agent, tenecteplase has emerged as a promising alternative due to its pharmacokinetic advantages. This systematic review and meta-analysis aim to compare the efficacy and safety of tenecteplase versus alteplase in AIS patients with LVO. Methods A systematic search was conducted across PubMed, Scopus, Web of Science, Cochrane Library, and Embase until February 2025. Studies comparing tenecteplase and alteplase in AIS patients with LVO were included. The primary outcomes were functional independence at 3 months (modified Rankin Scale [mRS] 0–1 and 0–2), mortality, and symptomatic intracranial hemorrhage (sICH). Secondary outcomes included any bleeding, adverse events, and overall complications. Pooled estimates were calculated using risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). Results A total of 14 studies (N = 9641 patients) were included, comprising 5898 patients receiving alteplase and 3743 receiving tenecteplase. No significant differences were observed in 3-month functional outcomes: mRS 0–1 (RR = 0.92, 95% CI: 0.78 to 1.1, P = 0.38) and mRS 0–2 (RR = 0.95, 95% CI: 0.83 to 1.08, P = 0.44). Mortality rates were comparable between groups (OR = 1.07, 95% CI: 0.88–1.30). No significant differences were found in intracranial hemorrhage (ICH) (OR = 1.25, 95% CI: 0.96–1.62), sICH (OR = 1.1, 95% CI: 0.91–1.33), or any bleeding (OR = 1.19, 95% CI: 0.9–1.57). The pooled OR for adverse events was 0.79 (95% CI: 0.53 to 1.17), indicating a comparable safety profile. Conclusion This meta-analysis supports the non-inferiority of tenecteplase compared to alteplase in LVO-associated AIS regarding efficacy and safety. While tenecteplase offers practical advantages, including single-bolus administration and potentially lower costs, further large-scale randomized controlled trials are needed to confirm these findings and optimize thrombolytic selection in stroke care.

The superior septal approach (SSA) was developed to improve mitral valve exposure during surgery, particularly in patients with complex anatomy. However, c

Background Hypertriglyceridemia and hypercholesterolemia are well-known risk factors for atherosclerotic cardiovascular disease (ASCVD), especially in patients already at elevated cardiovascular risk. Despite current treatment approaches, including lifestyle changes and medication, many individuals do not reach ideal lipid levels, emphasizing the need for new therapeutic options. Olezarsen, an antisense oligonucleotide targeting apolipoprotein C-III (ApoC-III) synthesis, has emerged as a promising candidate to reduce residual cardiovascular risk in these patients. Aim This systematic review and meta-analysis aimed to assess the effectiveness and safety of different dosages of Olezarsen in patients with high-risk hypertriglyceridemia. Additionally, it explored whether varying dosage regimens impacted lipid outcomes and adverse events. Methods Following PRISMA guidelines, a comprehensive search was conducted in PubMed, Scopus, Web of Science, and Cochrane Library for randomized controlled trials (RCTs) published in English. The studies included compared different doses of Olezarsen with placebo in high-risk hypertriglyceridemia patients. Primary outcomes were changes in triglycerides (TG), very-low-density lipoprotein cholesterol (VLDL-C), apolipoprotein B (ApoB), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and treatment-emergent adverse events (TEAE). Secondary outcomes included changes in non-HDL-C and total cholesterol (TC). The data were analyzed as mean differences (MD) or odds ratios (OR) using a random-effects model. Results Four RCTs (309 participants) were included. The pooled analysis demonstrated significant reductions in TG (MD = –76.11), VLDL-C (MD = –54.95 mg/dL), ApoB (MD = –12.40 mg/dL), non-HDL-C (MD = –18.03 mg/dL), and LDL-C (MD = –10.09 mg/dL) with Olezarsen treatment compared to placebo. Olezarsen also significantly increased HDL-C levels (MD = + 22.60 mg/dL), while total cholesterol remained unchanged. No significant differences in overall adverse events or drug-related adverse events were observed compared to placebo. Subgroup analysis revealed a dose-dependent effect on several lipid parameters without an increase in adverse events with higher doses. Conclusion Olezarsen effectively improves key lipid parameters, including TG, VLDL-C, ApoB, non-HDL-C, and LDL-C, while also safely raising HDL-C in patients with high-risk hypertriglyceridemia. Total cholesterol remained stable, and no increase in adverse events was noted. Further studies are needed to determine optimal dosing and long-term cardiovascular benefits.

Background Knee osteoarthritis (KOA) is one of the most common forms of joint degeneration, frequently resulting in persistent pain, reduced mobility, and impaired quality of life. The disease is characterized by the progressive breakdown of articular cartilage, synovial inflammation, and subchondral bone changes. Conventional management options such as analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroid injections, and surgical procedures are primarily aimed at alleviating symptoms rather than reversing or halting disease progression. In recent years, interest has grown in regenerative strategies, particularly the use of human adipose-derived mesenchymal stem cells (hAD-MSCs), due to their ability to modulate inflammation, promote tissue repair, and potentially regenerate damaged cartilage. These stem cells are favored for their ease of harvest, high yield, and ability to differentiate into chondrocytes. Despite their promising biological properties, the clinical benefit of intra-articular hAD-MSC therapy in KOA remains a subject of ongoing investigation, with varying outcomes reported across studies. Aim This systematic review and meta-analysis aims to assess the therapeutic efficacy of intra-articular hAD-MSC injections in individuals with knee osteoarthritis by analyzing data from randomized controlled trials. Methods An extensive search of the literature was performed in alignment with the PRISMA framework, using four major databases: PubMed, Scopus, Web of Science, and the Cochrane Library. Studies considered for inclusion were randomized controlled trials (RCTs) examining the effects of intra-articular human adipose-derived mesenchymal stem cell (hAD-MSC) therapy in individuals diagnosed with knee osteoarthritis (KOA). Risk of bias in the selected trials was evaluated using the Cochrane Risk of Bias 2 (ROB2) tool. Statistical pooling of data was conducted using a random-effects model via Review Manager (RevMan) version 5.3. Results A total of 11 RCTs, encompassing 510 patients, met the eligibility criteria for inclusion in the meta-analysis. Treatment with hAD-MSCs led to statistically significant improvements in WOMAC scores (mean difference [MD] = – 25.32, 95% confidence interval [CI] – 31.30 to – 19.34; p < 0.00001) and VAS pain ratings (MD = – 3.45, 95% CI – 3.74 to – 3.15; p < 0.00001). Furthermore, patient-reported quality of life showed meaningful enhancement following treatment (MD = 18.28, 95% CI 10.35–26.21; p < 0.00001). However, analysis of KOOS-Symptom domain scores did not show a statistically significant difference. The degree of heterogeneity differed between outcome measures. Conclusion This meta-analysis demonstrates that intra-articular administration of hAD-MSCs can effectively reduce pain and enhance joint function and quality of life in patients with knee osteoarthritis. These results support the potential of hAD-MSCs as a regenerative and disease-modifying therapeutic approach. Nevertheless, additional well-designed clinical trials are necessary to establish long-term safety and sustained clinical benefits.