The following recommendations should be implemented on a wider scale: i

The gap

Evidence profile

Sourced from the recommendations and future work and limitations of the source papers, classified as general, spanning 3 journals.

Supporting evidence — 3 representative gaps

• Iron Overload, Chelation Gaps and Marrow Injury in Beta-Thalassemia Major: A Cross-Sectional Study from Khyber Pakhtunkhwa, Pakistan (2026) · Zenodo (CERN European Organization for Nuclear Research) · doi

  The following recommendations should be implemented on a wider scale: i. Measuring CBC, reticulocyte count, and serum ferritin at every pre- transfusion visit and tracking longitudinally in BTM patients enrolled in thalassemia programmes. ii. Deferasirox as the preferred first-line chelation agent, its oral formulation and better compliance and should be initiated without interruption once ferritin exceeds 1000 ng/mL. for Page 166 https://pakjmcr.com/index.php/1/about

  generalrecommendations
  Keywords: ferritin following recommendations implemented wider scale measuring reticulocyte count serum every transfusion visit tracking longitudinally
• The Possible Hematological Cost of Metabolic Success: Do Incretin-Based Therapies Silently Trigger Anemia? (2026) · Medical Sciences · doi

  Current evidence does not establish incretin-based therapies as a class cause of anemia. Rather, selected observational and mechanistic findings raise the possibility that hema- tological outcomes may reflect an interaction between treatment-related changes in food intake, gastrointestinal physiology, iron absorption, weight loss, inflammation, kidney function, and baseline nutritional status. Moreover, evidence directly linking incretin therapy to clinically significant anemia remains limited and heterogeneous. The available clinical literature therefore supports a cautious, individualized interpretation rather than routine attribution of anemia to incretin therapy. Thus, prospective studies incorporating standardized definitions of anemia, iron status, nutritional biomarkers, gastrointestinal https://doi.org/10.3390/medsci14050577 Med. Sci. 2026, 14, 577 18 of 24 symptoms, dietary intake, kidney function, and longitudinal treatment exposure are needed to determine whether specific patient subgroups are at increased risk. In clinical practice, hematological and nutritional assessment should be individualized according to baseline risk factors and treatment-related clinical features rather than applied universally. Author Contributions: Conceptualization, M.M.; methodology, M.M., D.B. and I.M.; software, D.B.; validation, M.M., D.B. and I.M.; formal analysis, M.M. and I.M.; investigation, M.M., D.B. and I.M.; resources, M.M., D.B. and I.M.; data curation, M.M., D.B. and I.M.; writing—original draft preparation, M.M., D.B. and I.M.; writing—review and editing, M.M., D.B. and I.M.; visualization, M.M., D.B. and I.M.; supervision, M.M.; project administration, M.M.; funding acquisition, M.M. and I.M. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: No new data were created or analyzed in this study. Data sharing is not applicable to this article. Conflicts of Interest: The authors declare no conflicts of interest.

  generalfuture work
  Keywords: anemia incretin rather treatment nutritional clinical funding statement applicable evidence related intake gastrointestinal iron kidney
• Interleukin-6 Inhibition with Ziltivekimab in Chronic Kidney Disease–Associated Anemia: A Hypothesis-Generating Systematic Review and Meta-Analysis of Early-Phase Randomized Trials (2026) · SN Comprehensive Clinical Medicine · doi

  Serum ferritin demonstrated a small, non-significant increase (MD = 2.30 ng/mL, p = 0.82) under both models. This analysis represents the first pooled synthesis evaluat- ing IL-6 inhibition with ziltivekimab for anemia in CKD. SN Comprehensive Clinical Medicine (2026) 8:89 Key strengths include strict adherence to PRISMA 2020 guidelines, prospective protocol registration, comprehen- sive literature search and screening, and robust statistical methods. All included trials were high-quality RCTs as assessed by the Cochrane RoB 2.0 tool. Sensitivity analy- ses confirmed the robustness of outcomes, and GRADE was applied to assess certainty of evidence. Using a ran- dom-effects model with the Hartung–Knapp adjustment minimized the risk of false-positive results and provided conservative effect estimates. Optimal Information Size (OIS) calculations indicated that the analysis was suffi- ciently powered to detect clinically meaningful effects for hemoglobin.By evaluating both efficacy and safety, this meta-analysis offers a balanced, comprehensive assess- ment of ziltivekimab in CKD-associated anemia. Several important limitations should be noted. First, only three early-phase studies with a total of 324 participants were included, limiting statistical power and generaliz- ability. Second, treatment duration was short (12 weeks), with safety follow-up ranging from 24 to 32 weeks, which may not capture longer-term efficacy or safety. Third, the included trials involved heterogeneous populations (pre- dialysis and dialysis CKD), and outcomes are surrogate biomarkers rather than direct measures of clinical benefit. Finally, iron-related outcomes (serum iron and ferritin) showed wide prediction intervals, reflecting uncertainty regarding reproducibility. Overall, these findings should be interpreted as exploratory and hypothesis-generating, highlighting the need for larger, long-term trials to confirm efficacy, clarify safety, and define the potential role of ziltivekimab in CKD-related anemia.

  generallimitationsevidence 5/5
  Keywords: safety ziltivekimab anemia included trials outcomes efficacy serum ferritin first comprehensive clinical statistical assess effects

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