Search Results (17)

Background/Objectives: The prolonged M1-like pro-inflammatory polarization of macrophages is a key factor in the delayed healing of diabetic ulcers (DU). SIRT3, a primary mitochondrial deacetylase, has been identified as a regulator of inflammation and represents a promising new therapeutic target for DU treatment. Nonetheless, the efficacy of existing SIRT3 agonists remains suboptimal. Methods: Here, we introduce a novel compound, SZC-6, demonstrating promising activity levels. Results: SZC-6 treatment down-regulated the expression of inflammatory factors in LPS-treated RAW264.7 cells and reduced the proportion of M1 macrophages. Mitosox, IF, and JC-1 staining revealed that SZC-6 preserved cellular mitochondrial homeostasis and reduced the accumulation of reactive oxygen species. In vivo experiments demonstrated that SZC-6 treatment accelerated wound healing in diabetic mice. Furthermore, HE and Masson staining revealed increased neovascularization at the wound site with SZC-6 treatment. Tissue immunofluorescence results indicated that SZC-6 effectively decreased the proportion of M1-like cells and increased the proportion of M2-like cells at the wound site. We also found that SZC-6 significantly reduced MyD88, p-IκBα, and NF-χB p65 protein levels and inhibited the nuclear translocation of P65 in LPS-treated cells. Conclusions: The study concluded that SZC-6 inhibited the activation of the NF-χB pathway, thereby reducing the inflammatory response and promoting skin healing in diabetic ulcers. SZC-6 shows promise as a small-molecule compound for promoting diabetic wound healing. Full article

Background: Sodium zirconium cyclosilicate (SZC) is a novel potassium-binding agent with strong evidence supporting its efficacy in normalizing hyperkalemia. However, the long-term prognostic impact of SZC-integrated medical therapy in patients with systolic heart failure and baseline hyperkalemia remains uncertain. Methods: This study included patients with heart failure and a left ventricular ejection fraction (LVEF) of <50% who were prescribed SZC for hyperkalemia between July 2020 and February 2025. Patients who continued SZC therapy for two years or until February 2025 were classified into the SZC continuation group and followed from the initiation of SZC. Those who discontinued SZC during the study period were assigned to the SZC discontinuation group, with follow-up commencing from the point of cessation. The two-year cumulative incidence of all-cause mortality or hospital readmission was compared between the groups. Results: A total of 61 patients (median age: 79 years; 33 men; median LVEF: 42%) were included in the analysis. Serum potassium levels significantly decreased in the SZC continuation group (p < 0.001) but remained unchanged in the SZC discontinuation group (p = 0.23). The SZC continuation group demonstrated a trend toward a lower cumulative incidence of the primary outcome compared to the SZC discontinuation group (29% vs. 47%, p = 0.079). Additionally, in the SZC continuation group, the daily doses of renin-angiotensin system inhibitors and mineralocorticoid receptor antagonists increased significantly (p < 0.05 for both). Furthermore, LVEF improved significantly with SZC-integrated medical therapy (p = 0.011), whereas no such changes were observed in the SZC discontinuation group (p > 0.05 for all). Conclusions: Long-term SZC-integrated medical therapy was associated with the sustained normalization of hyperkalemia, optimization of heart failure pharmacotherapy, and improved clinical outcomes in patients with systolic heart failure and baseline hyperkalemia. These findings underscore the need for prospective randomized controlled trials in carefully selected patient populations to validate the benefits of SZC and establish its optimal supportive role in the management of systolic heart failure. Full article

Hyperattenuating contents detected in the gastrointestinal (GI) tract on CT scans are commonly seen and are almost always due to the purposeful ingestion of an oral contrast agent, usually barium- or iodine-based, used for evaluating the GI tract. Occasionally, other ingested material such as antacids or other medications, foreign objects, and medical devices can also be hyperattenuating. While these are usually correctly identified, these materials can potentially be misdiagnosed as a pathologic condition. Lokelma (sodium zirconium cyclosilicate (SZC)) is an increasingly used agent to treat hyperkalemia and has a hyperattenuating appearance on CT due to the presence of zirconium. However, this is not well known to the radiologic community. Here, we describe a case where SZC was seen in the GI tract on CT and misinterpreted as an acute GI bleed. A 72-year-old woman underwent single (portal venous) phase intravenous contrast-enhanced abdominal and pelvic CT after presenting to the ED with a lower GI bleed. The CT showed intraluminal hyperattenuation within the cecum, which was diagnosed prospectively as an active GI bleed. A CT angiogram of the abdomen and pelvis performed the following day for follow-up showed the hyperattenuating contents to be present on the non-IV contrast-enhanced series of the study, thereby proving that it was not due to active bleeding. Further investigation of the patient’s medical record showed that the patient was being treated with SZC for hyperkalemia, accounting for the hyperattenuating cecal contents. Awareness of the hyperattenuating appearance of SZC on CT by radiologists and clinical staff can help avoid confusion and misdiagnosis. Full article

(1) Background: Constipation is one of the most serious adverse effects of potassium-lowering agents and decreases patients’ quality of life. Sodium zirconium cyclosilicate (SZC) is a recently innovated potassium binder intended for patients with hyperkalemia. The impact of SZC on the worsening of constipation, as compared with conventional potassium binders, remains unknown. (2) Methods: Patients with hyperkalemia who continued SZC for over 3 months between July 2020 and May 2022 were included in this retrospective study. Patients who received other conventional potassium binders during the same period were included as a control group. Trends in the doses of anti-constipation agents during the 3-month therapeutic period were compared between the two groups as a surrogate for worsening constipation. (3) Results: A total of 50 patients (median age 74 years, 31 male) were included, consisting of 22 patients with SZC and 28 patients with other conventional potassium binders. All patients had hyperkalemia and chronic kidney disease at baseline. During the 3-month therapeutic period, serum potassium levels decreased significantly in both groups (p < 0.05 for both). The number of anti-constipation remained unchanged in the SZC group but tended to increase in the control group (p = 0.56 and p = 0.090, respectively). The total dose change in all anti-constipations was significantly lower in the SZC group than in the control group (p = 0.037). (4) Conclusions: Conventional potassium binders have a tendency to worsen constipation, whereas SZC may have the potential to improve hyperkalemia without worsening constipation. SZC may be recommended, particularly in elderly patients with ongoing or high-risk constipation. Full article

Background: Restriction of oral potassium intake is a necessary dietary intervention for managing chronic hyperkalemia. These dietary changes may have negative impacts on nutrition status, particularly in geriatric cohorts with multiple comorbidities. Sodium zirconium cyclosilicate (SZC) is a newly introduced potassium binder intended for patients with hyperkalemia. We aimed to investigate whether the improvements in hyperkalemia with SZC therapy and the liberation of potassium intake restriction may improve nutrition status in a primarily geriatric patient cohort with chronic hyperkalemia. Methods: Patients who were maintained on SZC therapy for at least 3 months were retrospectively studied. Following the initiation of SZC and improvement in hyperkalemia, instructions on the restriction of potassium intake were loosened according to the institutional protocol. The change in nutrition status during the 3 month therapeutic period using SZC was investigated by referencing the prognostic nutritional index score (PNI), geriatric nutritional risk index score (GNRI), and controlling nutritional status (CONUT) scores. Results: A total of 24 patients (median age 78 years, 58% men, median estimated glomerular filtration rate 29.8 mL/min//1.73 m²) were included. Serum potassium level decreased significantly from 5.4 (5.1, 5.9) to 4.4 (4.2, 4.9) mEq/L without any drug-related adverse events, including hypokalemia. Nutrition-related scores, including the PNI score, the GNRI score, and the CONUT score, improved significantly following 3 months of SZC therapy (p < 0.05 for all). Psoas muscle volume and average days for one movement also improved significantly during the therapeutic period (p < 0.05 for both). Conclusions: Mid-term SZC therapy and liberation of potassium intake restriction might improve nutrition status in geriatric patients with chronic hyperkalemia. Full article

Young children in resource-constrained settings are susceptible to zinc deficiency and its deleterious health effects. The objective of this secondary analysis was to evaluate the effects of the following six interventions on biomarkers of iron and zinc status among a subgroup of young children in Dhaka, Bangladesh, who participated in the Zinc in Powders Trial (ZiPT): (1) standard micronutrient powders (MNPs) containing 4.1 mg zinc and 10 mg iron, daily; (2) high-zinc (10 mg) and low-iron (6 mg) (HiZn LoFe) MNP, daily; (3) HiZn (10 mg) and LoFe (6 mg)/HiZn (10 mg) and no-iron MNPs on alternating days; (4) dispersible zinc tablet (10 mg), daily; (5) dispersible zinc tablet (10 mg), daily for 2 weeks at enrollment and at 12 weeks; (6) placebo powder, daily. At the end of the 24 week intervention period, children in the daily dispersible zinc tablet group exhibited a mean serum zinc concentration (SZC) of 92.5 μg/dL, which was significantly higher than all other groups except the HiZn LoFe MNP alternating group (81.3 μg/dL). MNPs containing 10 mg and 6 mg of iron had a similar impact on biomarkers of iron status, with no evidence of an adverse interaction with zinc. Full article

Background: Sodium zircon`ium cyclosilicate (SZC), a recently introduced potassium binder, is indicated to treat hyperkalemia. SZC is often terminated soon after the normalization of hyperkalemia in real-world clinical practice. We aimed to investigate the risk factors for the rapid recurrence of hyperkalemia following cessation of SZC. Methods: Patients in whom SZC was discontinued following an improvement in hyperkalemia were followed up for three months. The baseline characteristics that were associated with the rapid recurrence of hyperkalemia (>5.0 mEq/L of serum potassium levels within 3 months) were investigated. Results: A total of 44 patients terminated SZC following the normalization of hyperkalemia. The median age was 81 (69, 87) years old, and 59% were men. When evaluating baseline characteristics, a higher dose of renin-angiotensin system inhibitors was significantly associated with the recurrence of hyperkalemia (adjusted hazard ratio of 1.26, 95% confidence interval 1.02–1.69, p = 0.045) at a designated cutoff of 2.5 mg/day of equivalent enalapril dose. Conclusions: SZC should be considered for ongoing continuation after normalization of hyperkalemia, particularly in patients receiving a relatively higher dose of renin-angiotensin system inhibitors. Full article

Background: Sodium zirconium cyclosilicate (SZC), a newly introduced potassium binder, is indicated for treating hyperkalemia. SZC-incorporated up-titration of renin-angiotensin system inhibitors and mineralocorticoid receptor antagonists has been recommended for those with systolic heart failure, whereas SZC is often terminated following the improvement of hyperkalemia in real-world practice. We aimed to investigate the impact of SZC cessation on the recurrence of hyperkalemia. Methods: Patients with systolic heart failure, in whom SZC was discontinued following improvement in hyperkalemia, were studied and compared to those who had continued SZC. All patients were followed for one year or until August 2022. The recurrent rates of hyperkalemia were compared between the two groups. Results: A total of 30 patients (median age 83 years, 53% men, median left ventricular ejection fraction 42%) were included. The one-year cumulative incidence of recurrent hyperkalemia was 93% in the group who discontinued SZC versus 22% in those who continued SZC (p = 0.032). In the group where SZC was withdrawn, doses of renin-angiotensin system inhibitors and mineralocorticoid receptor antagonists were less up-titrated, echocardiographic evidence of reverse remodeling occurred less, and readmission due to worsening heart failure tended to be higher compared to those who remained on SZC therapy. Conclusions: SZC cessation was associated with recurrent hyperkalemia and suboptimal medical therapy optimization compared to continuation of SZC therapy. Full article

Heart failure (HF) is a worrisome cardiac pandemic with a negative prognostic impact on the overall survival of individuals. International guidelines recommend up-titration of standardized therapies in order to reduce symptoms, hospitalization rates, and cardiac death. Hyperkalemia (HK) has been identified in 3–18% of HF patients from randomized controlled trials and over 25% of HF patients in the “real world” setting. Pharmacological treatments and/or cardio-renal syndrome, as well as chronic kidney disease may be responsible for HK in HF patients. These conditions can prevent the upgrade of pharmacological treatments, thus, negatively impacting on the overall prognosis of patients. Potassium binders may be the best option in patients with HK in order to reduce serum concentrations of K⁺ and to promote correct upgrades of therapies. In addition to the well-established use of sodium polystyrene sulfonate (SPS), two novel drugs have been recently introduced: sodium zirconium cyclosilicate (SZC) and patiromer. SZC and patiromer are gaining a central role for the treatment of chronic HK. SZC has been shown to reduce K⁺ levels within 48 h, with guaranteed maintenance of normokalemia for up to12 months. Patiromer has resulted in a statistically significant decrease in serum potassium for up to 52 weeks. Therefore, long-term results seemed to positively promote the implementation of these compounds in clinical practice due to their low rate side effects. The aim of this narrative review is to delineate the impact of new potassium binders in the treatment of patients with HF by providing a critical reappraisal for daily application of novel therapies for hyperkalemia in the HF setting. Full article

Background: Sodium zirconium cyclosilicate (SZC), a newly introduced specific potassium binder, is introduced to treat hyperkalemia. However, the implications of SZC in up-titrating renin–angiotensin–aldosterone system inhibitors in patients with systolic heart failure remain unknown. Methods and Results: Patients with heart failure with left ventricular ejection fraction <50% and hyperkalemia who had completed 3-month SZC therapy were retrospectively included. Serum potassium levels, the dose of renin–angiotensin–aldosterone system inhibitors, and echocardiographic parameters during the 3-month SZC therapy as compared with the pretreatment 3-month period were investigated. A total of 24 patients (median 77 years old, 71% men, median left ventricular ejection fraction 41%) received a 3-month SZC therapy without any associated adverse events including hypokalemia. Compared with the pretreatment period, serum potassium levels decreased, doses of renin–angiotensin–aldosterone system inhibitors increased, and the left ventricular ejection fraction and plasma B-type natriuretic peptide levels improved following the 3-month SZC therapy (p < 0.05 for all). Conclusions: SZC may be a promising therapeutic option to improve hyperkalemia, indirectly allowing up-titration of renin–angiotensin–aldosterone system inhibitors and facilitating reverse remodeling in patients with heart failure with a left ventricular ejection fraction <50% and hyperkalemia. Full article

Some applications such as fuel cells or photovoltaic panels offer low output voltage, and it is essential to boost this voltage before connecting to the grid through an inverter. The Z-network converter can be used for the DC-DC conversion to enhance the output voltage of renewable energy sources. However, boosting capabilities of traditional Z-network boost converters are limited, and the utilization of higher parts count makes it bulky and expensive. In this paper, an efficient, high step-up, switched Z-source DC-DC boost converter (HS-SZC) is presented, which offers a higher boost factor at a smaller duty ratio and avoids the instability due to the saturation of inductors. In the proposed converter, the higher voltage gain is achieved by using one inductor and switch at the back end of the conventional Z-source DC-DC converter (ZSC). The idea is to utilize the output capacitor for filtering and charging and discharging loops. Moreover, the proposed converter offers a wider range of load capacity, thus minimizing the power losses and enhancing efficiency. This study simplifies the structure of conventional Z-source converters through the deployment of fewer components, and hence making it more cost-effective and highly efficient, compared to other DC-DC boost converters. Furthermore, a comparison based on the boosting capability and number of components is provided, and the performance of the proposed design is analyzed with non-ideal elements. Finally, simulation and experimental studies are carried out to evaluate and validate the performance of the proposed converter. Full article

Background: Zinc is an essential micronutrient that impacts host–pathogen interplay at infection. Zinc balances immune responses, and also has a proven direct antiviral action against some viruses. Importantly, zinc deficiency (ZD) is a common condition in elderly and individuals with chronic diseases, two groups with an increased risk for severe severe coronavirus disease 2019 (COVID-19) outcomes. We hypothesize that serum zinc content (SZC) influences COVID-19 disease progression, and thus might represent a useful biomarker. Methods: We ran an observational cohort study with 249 COVID-19 patients admitted in Hospital del Mar. We have studied COVID-19 severity and progression attending to SZC at admission. In parallel, we have studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) replication in the Vero E6 cell line modifying zinc concentrations. Findings: Our study demonstrates a correlation between serum zinc levels and COVID-19 outcome. Serum zinc levels lower than 50 µg/dL at admission correlated with worse clinical presentation, longer time to reach stability, and higher mortality. Our in vitro results indicate that low zinc levels favor viral expansion in SARS-CoV-2 infected cells. Interpretation: Low SZC is a risk factor that determines COVID-19 outcome. We encourage performing randomized clinical trials to study zinc supplementation as potential prophylaxis and treatment with people at risk of zinc deficiency. Full article

The objective of this study was to evaluate the difference of crop and livestock products regarding energy balances, greenhouse gas (GHG) emissions, carbon economic efficiency, and water use efficiency using a life cycle assessment (LCA) methodology on farms in three sub-oases within the Shihezi Oasis of China. The three sub-oases were selected within the Gobi Desert, at Shizongchang (SZC), Xiayedi (XYD), and Mosuowan (MSW), to represent the various local oasis types: i. Oasis; ii. overlapping oasis-desert; and iii. Gobi oasis. The results indicated that crop production in XYD Oasis had higher energy balances (221.47 GJ/ha), and a net energy ratio (5.39), than in the other two oases (p < 0.01). The production of 1 kg CW of sheep in XYD Oasis resulted in significantly higher energy balances (18.31 MJ/kg CW), and an energy ratio (2.21), than in the other two oases (p < 0.01). The water use efficiency of crop production in the SZC Oasis was lower than that of the XYD and MSW oases (p < 0.05). Alfalfa production generated the lowest CO₂-eq emissions (8.09 Mg CO₂-eq/ha. year) and had the highest water use efficiency (45.82 MJ/m³). Alfalfa (1.18 ¥/kg CO₂-eq) and maize (1.14 ¥/kg CO₂-eq) had a higher carbon economic efficiency than other crops (p < 0.01). The main sources of GHG emissions for crop production were fertilizer and irrigation. The structural equation modelling (SEM) of agricultural systems in the Shihezi Oasis showed that the livestock category significantly influenced the economic income, energy, and carbon balances. Full article

Serum zinc concentration (SZC) is used widely to assess population-level zinc status. Its concentration decreases during inflammatory responses, which can affect the interpretation of the results. This study aimed to re-estimate the prevalence of zinc deficiency in Malawi based on the 2015–2016 Malawi Micronutrient Survey (MNS) data, by adjusting SZC measures with markers of inflammation. SZC and inflammation data from 2760 participants were analysed. Adjustments were made using: (1) The Internal Correction Factor (ICF) method which used geometric means, and (2) The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) method, which used linear regression. Mean SZC values increased significantly when adjustments were made by either ICF or BRINDA (p < 0.001). The national prevalence of zinc deficiency decreased from 62% to 59%, after ICF adjustment, and to 52% after BRINDA adjustment. ICF and BRINDA values of SZC were highly correlated (p < 0.001, r = 0.99), but a Bland–Altman plot showed a lack of agreement between the two methods (bias of 2.07 µg/dL). There was no association between the adjusted SZC and stunting, which is a proxy indicator for zinc deficiency. Inflammation adjustment of SZC, using ICF or BRINDA, produces lower estimates of zinc deficiency prevalence, but the lack of agreement between the adjustment methods warrants further research. Furthermore, the lack of association between SZC and stunting highlights the need to explore other biomarkers and proxies of population zinc assessment. This study demonstrates the importance of considering inflammatory confounders when reporting SZC, to ensure accuracy and to support policy decision making. Full article

Background: Zinc is an essential micronutrient for human beings and its deficiency affects their normal growth and development. Objective: The main aim was to evaluate the effect of two doses of zinc supplementation (ZS) on the nutritional status in chronic kidney disease (CKD) children. Methods: A randomized-trial multicentric study was conducted in 48 CKD (23 females) patients under 18-years-old, for a year. At random, participants took 30 or 15 mg/day of ZS, respectively. Anthropometric measurements and biochemical analysis were performed. Hypozincemia was determined by serum zinc concentration (SZC) using atomic absorption spectrophotometry. The positive or negative change in patients’ body mass index (BMI) Z-score, serum albumin, zinc and C-reactive protein (CRP) levels were used to evaluate the effect of ZS. Results: Mean SZC was normal before and after ZS. Despite ZS, there were no significant changes in serum albumin, zinc and CRP levels. A positive and significant association was observed between SZC and serum albumin before (p = 0.000) and after (p = 0.007) ZS. In both groups of ZS, there was a small but positive and significant change in body mass and normalization in BMI Z-score, hypoalbuminemia, hypozincemia and high CRP, especially with 30 mg/day of ZS. Conclusions: Zinc supplementation may be beneficial for nutritional status in children and adolescents with CKD. Full article