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This study was published in PloS One journal by Yao-Shuang Li and colleagues. MASLD encompasses a spectrum of liver conditions, including non-alcoholic fatty liver disease (NAFLD), which has been linked to various metabolic disorders.

Researchers utilized mendelian randomization (MR) analysis, a method leveraging genetic variants associated with MASLD-related traits, to investigate causal relationships with cognition and dementia. Three MR methods (inverse-variance weighted, weighted median, and MR-Egger) were employed, along with sensitivity tests to assess the robustness of the results.

Key Findings:

• MR analysis suggested a positive causal association between MASLD confirmed by liver biopsy and liver fibrosis/cirrhosis with vascular dementia (VD).

• However, there was no evidence of a causal link between MASLD-related diseases and cognitive performance or other types of dementia (e.g., Alzheimer’s disease, dementia with Lewy bodies).

• Sensitivity tests supported the robustness of the results, indicating the reliability of the findings.

This study highlights a potential link between MASLD-related diseases, particularly liver fibrosis/cirrhosis, and an increased risk of vascular dementia. While further research is needed to confirm these findings and elucidate underlying mechanisms, this study contributes to our understanding of the broader health implications of MASLD.

Healthcare professionals should consider monitoring cognitive function in individuals with MASLD-related liver conditions, particularly those at risk for vascular dementia. Continued investigation into the relationship between liver health and cognitive outcomes is warranted to inform comprehensive patient care strategies.

Reference:

Li Y-S, Xia Y-G, Liu Y-L, Jiang W-R, Qiu H-N, Wu F, et al. (2024) Metabolic-dysfunction associated steatotic liver disease-related diseases, cognition and dementia: A two-sample mendelian randomization study. PLoS ONE 19(2): e0297883. https://doi.org/10.1371/journal.pone.0297883

The study found that protein metabolites found in nuts, fish, legumes, red and processed meat, poultry and eggs are associated with lower risks of chronic kidney disease, with fish having the most protective effect. “These metabolites are candidate biomarkers of dietary intake and may be critical for the primary prevention of CKD,” the researchers write.

The finding supports the recent nutritional guidelines recommending a Mediterranean diet, which includes fish as the main dietary protein source.

The urine excretion of nitrogen estimates the total protein intake, but biomarkers of specific dietary protein sources have been sparsely studied. Using untargeted metabolomics, Casey M. Rebholz, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, and colleagues aimed to study serum metabolomic markers of 6 protein-rich foods and to investigate whether dietary protein–related metabolites are associated with incident CKD in a prospective cohort study.

The study included 3,726 participants from the Atherosclerosis Risk in Communities study without CKD at baseline. Exposures were dietary intake of 6 protein-rich foods (fish, legumes, nuts, red and processed meat, poultry, and egg), and serum metabolites.

The primary outcome was incident chronic kidney disease defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 with ≥25% eGFR decline relative to visit 1, hospitalization or death related to CKD, or end-stage kidney disease.

Cross-sectional associations between protein-rich foods and serum metabolites were estimated by multivariable linear regression models. C statistics assessed the metabolites’ ability to improve the discrimination of highest versus lowest three quartiles of intake of protein-rich foods beyond covariates (clinical factors, demographics, intake of nonprotein food groups, and health behaviours). Cox regression models identified prospective associations between protein-related metabolites and incident chronic kidney disease.

The researchers reported the following findings:

· 30 significant associations were identified between protein-rich foods and serum metabolites (fish, n = 8; nuts, n = 5; legumes, n = 0; red and processed meat, n = 5; eggs, n = 3; and poultry, n = 9).

· Metabolites collectively and significantly improved the discrimination of a high intake of protein-rich foods compared with covariates alone (difference in C statistics = 0.051, 0.033, 0.003, 0.024, and 0.025 for nuts, fish, red and processed meat, eggs, and poultry-related metabolites, respectively).

· Dietary intake of fish was positively associated with 1-docosahexaenoylglycerophosphocholine (22:6n3), which was inversely associated with incident CKD (HR, 0.82).

To conclude, the researchers identified 30 associations between protein-rich foods and serum metabolites, including 8 associations that were substantiated by prior studies (CMPF, EPA, DHA, 4-vinylphenol sulfate, tryptophan betaine, 3-methylhistidine, ectoine, and creatine). Metabolites individually and collectively had a strong discrimination value for the dietary intake of protein-rich foods, especially CMPF, DHA, tryptophan betaine, 4-vinylphenol sulfate, 3-methylhistidine, and DPA. These metabolites improved the discrimination of the dietary intake of proteins beyond covariates (clinical factors, demographics, intake of nonprotein food groups, and health behaviours).

“One fish-related metabolite (1-docosahexaenoyl-GPC [22:6n3]) was linked inversely with incident CKD risk,” the researchers wrote. “These metabolites are candidate biomarkers of dietary intake, and 1-docosahexaenoyl-GPC (22:6n3), as a marker of fish intake, may be critical for the primary prevention of CKD.”

Reference:

Bernard, L., Chen, J., Kim, H., Wong, K. E., Steffen, L. M., Yu, B., Boerwinkle, E., Levey, A. S., Grams, M. E., Rhee, E. P., & Rebholz, C. M. (2024). Serum Metabolomic Markers of Protein-Rich Foods and Incident CKD: Results From the Atherosclerosis Risk in Communities Study. Kidney Medicine, 100793. https://doi.org/10.1016/j.xkme.2024.100793

“Statin treatment demonstrated a dose-dependent protective effect and was linked with a reduced risk of TB in bronchiectasis patients. These findings indicate that statins may play a role in reducing TB risk by modulating airway inflammation in this patient population,” the researchers wrote.

According to the researchers, this is the first clinical study reporting an association between statin use and TB risk in patients with bronchiectasis. In a prior animal study, statins were revealed to have a potent adjunctive role to anti-TB drugs by intensifying their activity through phenocopying macrophage activation and regulating phagosomal maturation.

Chronic airway diseases have been associated with an increased TB risk, however, data is limited in bronchiectasis patients. Statins have been shown to exhibit anti-inflammatory effects by modulating the inflammatory response. Therefore, Kuang-Ming Liao, Department of Internal Medicine, Chi Mei Medical Center Chiali Branch, Tainan, Taiwan, and colleagues investigated whether statin treatment could reduce TB risk in patients with bronchiectasis.

For this purpose, the research team conducted a retrospective cohort study using a nationwide population database of bronchiectasis patients who did not receive statin treatment. The defined daily dose (DDD) of statin, current or past statin user and statin exposure time was measured for the impact of statin use.

The study’s primary outcome was the incidence of new-onset tuberculosis. Considering of potential immortal time bias due to stain exposure time, Cox regression models with time-dependent covariates were employed to determine HRs for TB incidence among patients with bronchiectasis.

The study led to the following findings:

• Patients with bronchiectasis receiving statin treatment had a decreased risk of TB.
• After adjusting for age, sex, income, comorbidities and Charlson Comorbidity Index, statin users had a 0.59-fold lower risk of TB incidence compared with non-statin users.
• Compared with non-statin users, statin treatment was a protective factor against TB in users with a cumulative DDD greater than 180 per year, with an HR of 0.32.

In conclusion, the findings showed a reduced risk of tuberculosis with statins in bronchiectasis patients, exerting a dose-dependent protective effect. This protective effect was observed in patients of both sexes, different comorbidity levels, and all age groups.

The researchers suggest that healthcare providers should carefully assess the potential benefits of statin therapy in TB risk reduction while considering personal patient factors before incorporating statin use into their clinical practice.

“Nonetheless, there is a need for further prospective studies to obtain more information on the relationship between statin use and the risk of TB development,” the researchers concluded.

Reference:

Liao, M., Lee, S., Wu, C., Shu, C., & Ho, H. (2024). Association between statin use and tuberculosis risk in patients with bronchiectasis: A retrospective population-based cohort study in Taiwan. BMJ Open Respiratory Research, 11(1). https://doi.org/10.1136/bmjresp-2023-002077

The reduction in attack rates was observed regardless of the severity of the disease, the history of prior prophylaxis or the patient’s C1-inhibitor (C1-INH) level and function.

The findings were presented in five posters at the 2024 American Academy of Allergy, Asthma & Immunology (AAAAI) annual meeting, held at the Walter E. Washington Convention Center in Washington, D.C., from February 23-26, 2024. Three posters were cited in the announcement, which assessed real-world efficacy for those aged 12 years and up with hereditary angioedema.

“These additional analyses of real-world use of ORLADEYO show that any person living with HAE has the potential to experience a rapid, substantial and sustained reduction in their monthly attack rate with ORLADEYO,” according to Jonathan Bernstein, M.D., professor of medicine, department of internal medicine, division of allergy & immunology at the University of Cincinnati and partner of the Bernstein Allergy Group and Bernstein Clinical Research Center.

“From patients who live with severe disease to well-controlled patients and those who have a history of being treated with other long-term prophylaxis that carries a therapeutic burden, these data demonstrate that once patients begin oral, once-daily ORLADEYO, they can experience attack control for their treatment.”

Three posters highlight data collected through the sole-source pharmacy of BioCryst that show real-world effectiveness outcomes for patients aged 12 and above with HAE who initiated ORLADEYO in the United States. These analyses present the overall attack rate progression and attack rate progression stratified by severity (i.e., number of attacks at baseline), prior prophylaxis and C1-INH level and function.

“We are continuing to see strong disease control with ORLADEYO in the real world, including in patients with HAE who report differing baseline disease severities,” Dr. Ryan Arnold, chief medical officer of BioCryst, said in a statement.

He added, “These findings further demonstrate that ORLADEYO can help maintain disease control in patients with lower baseline attack rates and further reduce attack rates in patients with more active disease. We continue to be encouraged by the consistent, building body of real-world evidence demonstrating the significant benefit that our oral, once-daily prophylactic therapy can provide to people living with HAE.”

The first study was titled ‘Berotralstat Prophylaxis Reduces HAE Attack Rates Regardless of Baseline Attacks: Real-World Outcomes,’ in which the participants known to have C1-INH deficiency receiving long-term prophylaxis with berotralstat showed rapid and sustained reductions in their monthly rates of HAE attacks.

The researchers found a dip in the median rates of HAE below baseline in the first 90 days of treatment. They added that these rates continued to be consistently reduced over subsequent 90-day intervals for up to 18 months and that this occurred regardless of attack severity at the point of baseline.

In the analysis titled ‘Consistently Low Hereditary Angioedema Attack Rates with Berotralstat Regardless of Prior Prophylaxis: Real-World Outcomes,’ the researchers showed substantial reductions in HAE attacks among participants who had previously attempted to use other prophylactic therapies and then started berotralstat.

These reductions were sustained and observed irrespective of subjects’ previous treatments, such as subcutaneous C1-INH, lanadelumab, and androgens. The researchers also noted that participants given lanadelumab previously saw a decrease in median monthly attack rate from 1.00 at the point of baseline to 0.33 in the initial 90 days of treatment, and this rate stayed below baseline through days 451-540.

The second study, titled ‘Real-World Effectiveness of Berotralstat in HAE With and Without C1-Inhibitor Deficiency,’ led to results suggesting that participants with normal C1-INH levels and subjects showing deficiency in C1-INH reported monthly HAE attack rate reduced with the use of berotralstat. Specifically, the investigators found that the drug led to a substantial decrease in these rates which were sustained over time.

The participants’ median attack rates among those with normal C1-INH dipped from 3.00 at the point of baseline to 1.00 on days 1-90. They also revealed that participants with C1-INH deficiency saw rates go from 1.33 to 0.50; the results persisted through days 451-540.

“From patients who live with severe disease to well-controlled patients and those who have a history of being treated with other long-term prophylaxis that carries a therapeutic burden, these data show that once patients begin oral, once-daily (berotralstat), they can experience attack control throughout their treatment,” Bernstein concluded.