Effect of Dietary Supplements Which Upregulate Nitric Oxide on Walking and Quality of Life in Patients with Peripheral Artery Disease: A Meta-Analysis.

This systematic review pooled evidence from randomised controlled trials (RCTs) on the effectiveness of dietary upregulators of nitric oxide (NO) in improving the walking and quality of life of patients with peripheral artery disease (PAD). RCTs examining the effect of dietary upregulators of NO in patients with PAD were included. The primary outcome was the maximum walking distance. Secondary outcomes were the initial claudication distance, the six-minute walking distance, quality of life, the ankle-brachial pressure index (ABI), adverse events and risk of mortality, revascularisation or amputation. Meta-analyses were performed using random effects models. The risk of bias was assessed using Cochrane's ROB-2 tool. Leave-one-out and subgroup analyses were conducted to assess the effect of individual studies, the risk of bias and intervention type on pooled estimates. Thirty-four RCTs involving 3472 participants were included. Seven trials tested NO donors, nineteen tested antioxidants, three tested NO synthase inducers and five tested enhancers of NO availability. Overall, the dietary supplements significantly improved the initial claudication (SMD 0.34; 95%CI 0.04, 0.64; p = 0.03) but not maximum walking (SMD 0.13; 95%CI -0.17, 0.43; p = 0.39) distances. Antioxidant supplements significantly increased both the maximum walking (SMD 0.36; 95%CI 0.14, 0.59; p = 0.001) and initial claudication (SMD 0.58; 95%CI 0.26, 0.90; p < 0.001) distances. The dietary interventions did not improve the physical function domain of the Short Form-36 (SMD -0.16; 95%CI -0.32, 0.00; p = 0.38), ABI or risk of adverse events, mortality, revascularisation or amputation. Dietary NO upregulators, especially antioxidants, appear to improve the initial claudication distance in patients with PAD. Larger high-quality RCTs are needed to fully examine the benefits and risks of these treatments. PROSPERO Registration: CRD42022256653.

Iron overload in lower international prognostic scoring system risk patients with myelodysplastic syndrome receiving red blood cell transfusions: Relation to infections and possible benefit of iron chelation therapy.

BACKGROUND: An increased incidence of infections and infectious mortality has been reported in myelodysplastic syndromes (MDS) patients receiving red blood cell (RBC) transfusions. METHODS: We examined incidence of infections requiring antibiotics, antifungal or antiviral medications in transfused lower International Prognostic Scoring System (IPSS) risk MDS patients and whether this differed with iron chelation therapy (ICT). RESULTS: 138 transfused MDS patients were lower IPSS risk. 59 received ICT; median duration was 13 months. There was no significant difference between groups in neutrophil count at first RBC transfusion or first infection. Infections included: bacterial, n = 88; viral; fungal; and mycobacterial; n = 2 each. In ICT and non-ICT patients, respectively, infections were (number [%]): patients, 23 (40.0%) and 22 (27.8%); episodes (median [range]), 2 (1-6) and 2 (1-5); hospitalizations, 16 (27.1%) and 8 (10.1%); and deaths, 0 (0%) and 1 (1.3%), p = NS for all. Median overall survival (OS) from first RBC transfusion was superior in ICT patients, p = 0.01, and remained significant in a multivariate analysis (MVA), p = 0.003. Median time to first infection (TTI) was 27 and 7.8 months, respectively, p < 0.0001, and ICT remained significant for TTI in an MVA, p = 0.02, hazard ratio 0.3. For ICT patients with blast count <5%, TTI was significantly superior (p = 0.004). CONCLUSIONS: In this retrospective analysis, for lower IPSS risk MDS patients receiving RBC transfusions, though number and type of infections were similar between groups and despite similar neutrophil counts, time to first infection was significantly longer in ICT patients (p < 0.0001). These results should be confirmed in larger, prospective analyses.

Iron chelation therapy in lower IPSS risk myelodysplastic syndromes; which subtypes benefit?

BACKGROUND: Analyses suggest MDS patients with higher serum ferritin levels (SF) have inferior overall survival (OS), in one study across MDS subtypes. Multiple analyses suggest those with high SF receiving iron chelation therapy (ICT) have superior OS, but which MDS subtypes benefit from ICT remains undefined. METHODS: We performed survival analyses of MDS subtypes by receipt of ICT. RESULTS: 182 MDS were lower IPSS risk and received red blood cell (RBC) transfusions; 63 received ICT. For the entire cohort, receiving ICT independently predicted superior OS in a multivariate analysis (hazard ratio for death 0.3, p=0.01). Features differing for ICT and non-ICT patients, respectively, were: age; IPSS risk group; number of RBC units transfused; and SF, p≤0.03 for all. At a median follow up of 76.5 and 28.4 months, 65.1% and 63.0% were alive. Median OS (months) for ICT and non-ICT patients was: RA, 140.9 and 36.3, p=0.0008; RARS/RARS-t, 133.4 and 73.3, p=0.02. For RCMD/RCMD-RS, p=NS, however, 3 (20%) had significant erythroid improvement with ICT; other subtypes had small numbers. DISCUSSION: In this retrospective analysis, RA and RARS/RARS-t patients receiving ICT had superior OS to non-ICT patients. These findings should be verified and other MDS subtypes examined in larger prospective analyses.