Search Results (2,874)

Background/Objectives: Circulating amino acid concentrations and their excretion can provide insights into dietary protein intake and metabolism. Alterations in amino acid homeostasis occur in various disorders due to nutritional imbalances or metabolic changes, including obesity. A ketogenic diet (KD) has gained popularity for weight management; however, its metabolic effects are not fully known. Therefore, the aim of this study was to evaluate the effect of an eight-week, energy-restricted Mediterranean-type KD on the amino acid metabolism in women with overweight and class I obesity. Methods: A randomized, single-center, controlled trial was conducted with 80 women with a BMI of 25.5–35 in age between 18 and 45 years, without any chronic diseases. Randomly divided women received food catering with approximately 1750 kcal daily for eight weeks, containing KD or standard diet (STD), respectively. The concentration of amino acids was assessed by gas chromatography-mass spectrometry after the derivatization with chloroformate in serum and urine collected at the baseline, after 4 weeks, and at the end of the intervention. Results: The results collected from 66 participants were included in the final analyses. Independent of diet type, weight reduction was associated with increased circulating α-aminobutyric acid and decreased proline, glutamate, and tyrosine. The KD led to lower concentrations of alanine, methionine, threonine, and tryptophan, alongside higher levels of branched-chain amino acids (BCAA) and α-aminobutyric acid compared to the STD. Urinary amino acid excretion decreased after weight reduction. KD was associated with higher urinary excretion of BCAA and β-aminoisobutyric acid. Conclusions: In summary, both weight reduction and KD significantly affect the amino acid metabolism, which might have implications for inflammation, oxidative stress, and cardiometabolic risk. Full article

Background/Objectives: Type 2 diabetes (T2D) is a chronic metabolic disorder closely linked to cardiovascular disease and obesity and notably influenced by lifestyle and dietary patterns. The Mediterranean diet has well-established benefits across multiple cardiometabolic risk factors, including those relevant to diabetes. This study aimed to investigate the degree to which adults with T2D adhere to a Mediterranean dietary pattern and to examine how such adherence relates to glycemic and lipidemic regulation. Methods: This cross-sectional study included 100 adults with T2D (54 men and 46 women). Adherence to the Mediterranean diet was assessed using the Mediterranean Diet Score (MDS). Demographic, anthropometric, lifestyle, and clinical data were collected, and glycemic and lipid parameters were analyzed. Associations between Mediterranean diet adherence and metabolic outcomes were examined using correlation analyses and multivariable regression models adjusted for relevant confounders. Results: Most participants showed low adherence to the Mediterranean diet. A significant inverse association was observed between Mediterranean diet adherence and hemoglobin A1c (HbA1c) levels, with individuals scoring ≤35 on the MDS demonstrating higher HbA1c levels. Similar trends were observed in the lowest tertile of adherence. Notably, each one-point increase in MDS predicted a 0.13% reduction in HbA1c. In multivariable regression analyses, Mediterranean diet adherence remained the strongest predictor of glycemic control, independent of age, body mass index (BMI), sex, smoking status, physical activity and the number of antidiabetic treatments. Higher adherence was also significantly associated with lower low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels, as well as higher high-density lipoprotein cholesterol (HDL) concentrations. Conclusions: Greater adherence to the Mediterranean diet is independently associated with improved glycemic regulation and a more favorable lipid profile in adults with T2D. These findings support the Mediterranean diet as a valuable non-pharmacologic strategy for optimizing metabolic outcomes in people with T2D. Full article

Background and Objectives: Obesity has been increasing sharply worldwide and is related to diabetes, cardiovascular diseases, liver disease, and cancer. Sleeve gastrectomy is the most used surgical approach to reduce body weight and treat metabolic implications observed in patients with moderate-to-severe obesity. On the other hand, this procedure affects the musculoskeletal system, and investigating skeletal muscle is not routinely recommended for bariatric surgery. This study aimed to evaluate the psoas muscle in patients in the preoperative period of sleeve gastrectomy and six months after the procedure using abdominal computed tomography scans. Materials and Methods: This clinical, exploratory, and observational study, with a prospective longitudinal observational study design, was conducted at a single center with 31 women who underwent sleeve gastrectomy. The evaluations were performed before and after six months of the procedures. Results: Anthropometric, muscle strength, hepatic ultrasound, and psoas computerized tomography evaluations were performed. A significant reduction in body weight, body mass index, waist, neck, and calf circumference was observed. There was also a substantial reduction in right-hand strength and the area and index of the psoas muscle (but with an increase in density). Most presented a routine abdominal ultrasound. Conclusions: Our results suggest that muscle evaluation provides valuable information for clinical monitoring before and after bariatric surgery, helping to identify potential risks and guide multidisciplinary follow-up. Psoas muscle area and psoas muscle index decreased, but psoas muscle density increased, all significantly. These results indicate that conducting a muscle evaluation is helpful for patients undergoing bariatric surgery, supporting the use of the clinical approach before and after the procedure, predicting possible complications, and providing more accurate prognoses. Full article

Purpose: With the addition of palbociclib to endocrine therapy, many hormone receptor-positive (HR+) metastatic breast cancer (mBC) patients experience toxicities that can lead to dose reductions and cycle delays. We examined the actual doses of palbociclib received by patients and their treatment responses. These dose adjustments, made at the physician’s discretion, are not always consistent with pharmaceutical company recommendations. The aim of this study was to assess the influence of dose adjustments on dose intensity and treatment response in our patients. Methods: Records of patients with HR+ mBC treated with palbociclib between December 2016 and January 2019 at the Sainte-Catherine Institute were retrospectively reviewed. Dose intensity was defined as the total dose of palbociclib received by each patient during the first six months of treatment. Anticipated dose reductions and extended cycle delays were recorded. Treatment response at six months and survival were assessed using statistical analyses. Results: A total of 131 women were included; the median age was 67 years. Forty-six patients (35%) experienced an anticipated dose reduction or an extended cycle delay during the first six months of treatment. Logistic regression analysis showed that factors correlated with six-month treatment response included anticipated dose reduction or extended cycle delay (OR = 14.6, 95% CI 3.74–97.4, p < 0.001), cycle delay > 4 weeks (OR = 5.94, 95% CI 1.58–21, p = 0.01), initial dosage < 125 mg (OR = 4.09, 95% CI 1.13–13.7, p = 0.034), and six-month dose intensity < 14,250 mg (OR = 26.0, 95% CI 4.91–481, p < 0.001). Conclusions: In this real-world assessment of clinical outcomes in French patients with HR+ mBC treated with palbociclib, a palbociclib dose intensity lower than recommended—particularly due to cycle delays longer than four weeks—was associated with an increased risk of six-month disease progression. Full article

Prediabetes is a serious and major global problem afflicting approximately 21% of the world’s population. It is the intermediate stage between normal glucose levels and type 2 diabetes mellitus (T2DM). Prediabetes is associated with major complications including the development of T2DM and increased cardiovascular disease (CVD). It can be easily diagnosed with an inexpensive plasma glucose level and/or a hemoglobin A1c (HbA1c) measurement. The mainstay of treatment is intensive lifestyle (ILS) intervention, including reduction in calories, especially saturated fats, refined carbohydrates, etc., coupled with regular physical activity of 150 min per week since ILS changes, with at least a 5% weight loss, have been shown to reduce progression to T2DM in multiple studies globally. Also, metformin therapy has been shown to prevent the progression to T2DM. In conclusion, serious consideration by guideline committees to classify prediabetes as a disease is highly recommended based on its global burden, easy and cost-effective diagnosis, association with serious conditions of diabetes and CVD, and effective ILS intervention. Therapy targeting those at an especially high risk for T2DM, such as persons with impaired glucose tolerance (IGT), impaired fasting glucose (IFG) with values ≥ 110 mg/dL (6.1 mmol/L), and/or HbA1c ≥ 6.0% (42 mmol/mol) coupled with overweightness or obesity. Full article

Osteoporosis and chronic conditions such as type 2 diabetes mellitus, cardiovascular disease, heart failure, and chronic kidney disease share several common biological mechanisms, including chronic inflammation, oxidative stress, hormonal dysregulation, and metabolic alterations. In this context, multimorbidity presents an increasing clinical challenge, particularly in older populations, where osteoporosis remains frequently underdiagnosed and undertreated. This review aims to explore the complex interplay between skeletal fragility and cardiometabolic diseases, emphasizing the role of nutritional deficiencies (such as iron and vitamin C), shared molecular pathways (advanced glycation end-products, Renin–Angiotensin–Aldosterone System, RANK Ligand, RANK), and the systemic impact of chronic inflammation and tissue hypoperfusion. The review also addresses the effects of various drug classes—antidiabetics, antihypertensives, anticoagulants, and anti-osteoporotic agents—on bone metabolism and cardiovascular risk. Special focus is given to the implementation of integrated and personalized care models, particularly multidisciplinary team-based approaches, which have demonstrated significant reductions in mortality and refracture rates, despite their still limited adoption in clinical practice. In conclusion, this review highlights the shared mechanisms between osteoporosis and cardiometabolic conditions in the context of multimorbidity, underscoring persistent clinical challenges related to diagnosis, drug interactions, and care fragmentation that warrant further research into integrated care models. Full article

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity, mortality, and healthcare utilization. Lung volume reduction surgery improves outcomes in a select cohort but portends high morbidity. Bronchoscopic lung volume reduction (BLVR) is a less invasive, reversible manner of lung volume reduction, using one-way valves to improve lung function, quality of life, and exercise capacity. Nevertheless, knowledge gaps persist regarding factors that predict procedural success. Methods: We retrospectively reviewed 142 patients who underwent BLVR at the University of Chicago between December 2018 and July 2024 to assess the relationship between comorbidities and procedural outcomes. Using logistic and multinomial regression, we determined odds ratios (ORs) for a binary outcome of success and failure and relative risk ratios (RRRs) for failure sub-categories relative to procedural success. Results: We observed a procedural success rate of 48.1% and pneumothorax prevalence of 21.8%. After adjusting for age, sex, race, and body mass index (BMI), comorbidities associated with procedural failure included chronic kidney disease (CKD), congestive heart failure (CHF), anemia, and a BMI, Obstruction, Dyspnea and Exercise (BODE) Index of 5 or greater. Obstructive sleep apnea (OSA) was associated with procedural success. Conclusions: Comorbidities associated with dyspnea appear to have a significant effect on procedural success in BLVR. Full article

Background: Cardiovascular diseases (CVD) are the leading global cause of death, disproportionately affecting Latin America. This study evaluated the impact of a contextualized workplace intervention, adapted from the Diabetes Prevention Program (DPP), on reducing cardiovascular risk (CVR) in a Latin American population. Methods: A quasi-experimental, pre-post study was conducted with 100 adults (34 males, 66 females) affiliated with the social security system. The 16-week “Transforma tu vida con cambios diarios” program, included ten sessions focused on motivation, healthy eating and physical activity. Sociodemographic, anthropometric, clinical, and biochemical parameters were measured before and after the intervention. CVR was estimated as a 10-year risk percentage using the non-laboratory Globorisk model. Analysis included paired t-test and Cohen’s d effect sizes. Results: Significant improvements (p < 0.05) were associated with the intervention. The predicted mean CVR score decreased from 8.03% to 6.71% (p = 0.03, d = 0.658). Reductions were observed in weight (73.1 to 71.7 kg, p < 0.001, d = 0.424), BMI (29.0 to 28.5 kg/m², p < 0.001, d = 0.363), and physical inactivity (60% to 39%, p = 0.001). A moderate-low clinical impact was found for systolic blood pressure (124.9 to 121.2 mmHg; p = 0.003, d = 0.301) and glucose (103.3 to 101.1 mg/dL; p = 0.04, d = 0.218) and HDL cholesterol (51.5 to 54.9 mg/dL; p = 0.02, d = −0.286) showed significant but small effects. Conclusions: The intervention was associated with favorable changes in clinical and anthropometric indicators. The results provide preliminary evidence that logistical adaptation to the workplace can effectively reach at-risk Latino populations, with weight and BMI improvements reflecting the program’s strong physical activity component. Full article

Background and Objectives: Lung cancer in never-smokers (LCINS) has become a major global health concern, ranking as the fifth leading cause of cancer-related mortality. Unlike smoking-related lung cancer, LCINS arises from complex interactions between environmental carcinogens and distinct genomic alterations. This review summarizes current evidence on environmental risks, molecular features, and therapeutic progress shaping lung cancer management. Methods: A narrative review was conducted to examine risk factors for lung cancer in non-smokers. Studies reporting driver mutations in never-smokers and smokers were identified across major lung cancer histological subtypes, including small-cell lung cancer (SCLC), lung adenocarcinoma (LUAD), squamous cell carcinoma (SCC), and large-cell carcinoma (LCC). In addition, PubMed was searched for phase III trials and studies on targeted therapies related to driver mutations published between 2016 and 2025. Results: Environmental factors such as cooking oil fumes, radon, asbestos, arsenic, and fine particulate matter (PM_2.5) are strongly associated with LCINS through oxidative stress, DNA damage, and chronic inflammation. EGFR, PIK3CA, OS9, MET, and STK11 mutations are characteristic of never-smokers, in contrast to TP53 mutations, which are more common in smokers. Recent advances in targeted therapy and immunotherapy have improved survival and quality of life, emphasizing the importance of molecular profiling for treatment selection. Conclusions: LCINS represents a distinct clinical and molecular entity shaped by complex interactions between environmental exposures and genetic susceptibility. Genetic alterations promote tumor immune evasion, facilitating cancer development and progression. Continued advances in air quality control, molecular diagnostics, and precision therapies are essential for prevention, early detection, and reduction of the global disease burden. Full article

Background: High residual platelet reactivity (HRPR) and persistent dyslipidemia remain important unmet needs in cardiovascular risk management, particularly in patients undergoing coronary revascularization. Despite intensive lipid-lowering and antiplatelet therapy, a substantial proportion of patients fail to reach recommended low-density lipoprotein cholesterol (LDL-C) targets or exhibit inadequate platelet inhibition. Inclisiran, a PCSK9-targeting small interfering RNA, represents an emerging approach for long-term LDL-C reduction. Methods: A narrative review of the literature published between 2009 and 2025 was performed using PubMed, Scopus, Web of Science, and MEDLINE. Studies evaluating the addition of inclisiran to standard lipid-lowering therapy in patients with dyslipidemia and HRPR, assessed using the VerifyNow assay, were included. Illustrative clinical cases from Kazakhstan were analyzed to demonstrate real-world changes in LDL-C levels and platelet reactivity following insufficient response to conventional treatment. The review had a descriptive design. Results: Available evidence indicates that a significant proportion of high- and very-high-risk patients do not achieve LDL-C targets or are unable to tolerate high-intensity statin therapy. Inclisiran consistently induces sustained reductions in LDL-C and circulating PCSK9 levels. Emerging data suggest a potential indirect modulation of platelet reactivity associated with intensive lipid lowering. In patients at extreme cardiovascular risk—including those after coronary artery bypass grafting (CABG) and with long-standing multivessel coronary artery disease—inclisiran therapy was associated with marked LDL-C reduction and a trend toward normalization of platelet reactivity. Conclusions: Assessment of platelet function using the VerifyNow assay may improve identification of residual thrombotic risk in patients with advanced atherosclerotic disease. Inclisiran appears to be a promising adjunctive therapy for dyslipidemic patients with persistently elevated cardiovascular risk and HRPR despite standard treatment. Further prospective studies are warranted to clarify the relationship between intensive LDL-C lowering, platelet reactivity, and clinical outcomes, and to optimize integrated lipid-lowering and antiplatelet strategies. Full article

Background: Tumor necrosis factor-α (TNFα) inhibitors have significantly improved outcomes in children with non-systemic juvenile idiopathic arthritis (JIA), achieving long-term clinical remission for many patients. However, the optimal strategy for TNF-α inhibitor withdrawal remains unknown, whether through abrupt discontinuation, gradual dose reduction, or interval extension. Objective: We aim to identify patient-, disease-, and treatment-related predictors of successful TNF-α inhibitor withdrawal in children with non-systemic JIA. Methods: In this prospective, randomized, open-label, single-center study, 76 children with non-systemic JIA in stable remission for ≥24 months on etanercept or adalimumab were enrolled. At the time of TNF-α inhibitor discontinuation, all patients underwent a comprehensive evaluation, including a clinical examination, laboratory tests (serum calprotectin [S100 proteins] and high-sensitivity C-reactive protein [hsCRP]), and advanced joint imaging (musculoskeletal ultrasound and magnetic resonance imaging [MRI]) to assess subclinical disease activity. Patients were randomized (1:1:1, sealed-envelope allocation) to one of three predefined tapering strategies: (I) abrupt discontinuation; (II) extension of dosing intervals (etanercept 0.8 mg/kg every 2 weeks; adalimumab 24 mg/m² every 4 weeks); or (III) gradual dose reduction (etanercept 0.4 mg/kg weekly; adalimumab 12 mg/m² every 2 weeks). Follow-up visits were scheduled at 3, 6, 9, 12, and 18 months to monitor for disease relapse. Results: Higher baseline Childhood Health Assessment Questionnaire (CHAQ) scores (≥2), elevated serum calprotectin [S100 proteins] and hsCRP levels at withdrawal, imaging evidence of subclinical synovitis, and a history of uveitis were all significantly associated with increased risk of flare. No significant associations were found for other clinical or demographic characteristics. Conclusions: Early significant clinical response, absence of subclinical disease activity, and concomitant low-dose methotrexate therapy were key predictors of sustained drug-free remission. These findings may inform personalized strategies for biologic tapering in pediatric JIA. Full article

Vitamin D is involved in immune regulation through effects on innate and adaptive immune responses mediated by vitamin D receptor activation within immune cells. Experimental and translational studies support its role in promoting regulatory T-cell activity, modulating Th1/Th17 responses, and influencing autoantibody production. At the population level, low serum 25-hydroxyvitamin D concentrations are consistently associated with an increased risk of autoimmune diseases, including autoimmune thyroid disorders such as Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), suggesting a potential preventive association. In contrast, clinical evidence from interventional studies in patients with established disease is heterogeneous. Although vitamin D supplementation has been associated with reductions in thyroid autoantibody titers in some studies—particularly in patients with HT and baseline vitamin D deficiency—consistent effects on thyroid function, disease progression, or relapse prevention have not been demonstrated. Overall, current evidence supports vitamin D deficiency as a potentially modifiable risk marker rather than a confirmed disease-modifying therapeutic target in autoimmune thyroid diseases, highlighting the need for further studies focused on clinically meaningful outcomes. Full article

Metabolic syndrome (MetS) is a multifactorial disorder characterized by central obesity, insulin resistance, dyslipidemia, and hypertension, all of which increase the risk of type 2 diabetes and cardiovascular diseases. This study investigates the potential complementary effects of the standardized green and black ADM ComplexTea Extract (CTE) and the heat-treated postbiotic (BPL1^® HT) on the cardiometabolic alterations associated with MetS in a murine model. C57BL/6J mice were fed a high-fat/high-sucrose (HFHS) diet and treated with CTE, BPL1^® HT, or their combination for 20 weeks. Metabolic, inflammatory, oxidative, vascular parameters, and fecal microbiota composition were assessed. Both CTE and BPL1^® HT individually attenuated weight gain, organ hypertrophy, insulin resistance, and inflammation. However, their combined administration exerted synergistic effects, fully normalizing body weight, adipocyte size, lipid profiles, HOMA-IR index, and insulin sensitivity to levels comparable to lean controls. Co-treatment also restored PI3K/Akt signaling in liver and muscle, reduced hepatic steatosis, and normalized the expression of inflammatory and oxidative stress markers across multiple tissues. Furthermore, vascular function was significantly improved, with enhanced endothelium-dependent relaxation and reduced vasoconstrictor responses, particularly to angiotensin II. CTE, BPL1^®HT, and the blend prevented bacterial richness reduction caused by HFHS; the blend achieved higher bacterial richness than mice in Chow diet. Additionally, the blend prevented the increase in Flintibacter butyricus, which is associated with MetS clinical parameters, and showed a tendency to increase the abundance of Bifidobacterium. These findings suggest that the combination of CTE and BPL1^® HT offers a potential nutritional strategy to counteract the metabolic and cardiovascular complications of MetS through complementary mechanisms involving improved insulin signaling, reduced inflammation and oxidative stress, enhanced vascular function, and modulation of gut microbiota. Full article

Background: Metabolically associated fatty liver disease (MASLD) constitutes a major burden. Glucagon-like peptide-1 agonists (GLP-1) could improve hepatic steatosis as well as weight loss. However, the effect of GLP-1 agonists on patients with and without diabetes and the effect of newer drugs (dual and triple agonists) are unclear. Objective: To investigate the effect of GLP-1 agonists, including dual and triple agonists, in patients with metabolic-associated liver steatosis and steatohepatitis, while exploring their effect on patients with and without type 2 diabetes. Methods: We searched PubMed, Scopus, and Web of Science in October 2025 for randomized parallel controlled trials that investigated the effect of GLP-1 agonists in patients with MASLD or metabolic-associated steatohepatitis (MASH). We assessed the quality of the included studies using Cochrane ROB2. We performed the analysis using RevMan 5.4. We performed subgroup analysis based on the status of diabetes, the control group, and the class of GLP-1 agonist (single, dual, or triple). Results: We included twenty studies. Compared to the control group, GLP-1 agonists were associated with a statistically significant increase in the resolution of MASH without worsening fibrosis (RR 3.03, p < 0.0001) and at least one stage of liver fibrosis without the worsening of MASH compared to the control group (RR: 1.45, p < 0.00001). GLP-1 agonists were associated with a statistically significant weight reduction (SMD −1.11, p < 0.0001), glycosylated hemoglobin (SMD −0.81, p < 0.00001), levels of aspartate aminotransferase (SMD −0.48, p = 0.008), and alanine aminotransferase (SMD −0.54, p = 0.008). However, in patients without type 2 diabetes, GLP-1 agonists had no significant effect on weight loss (SMD −0.97, p = 0.12) or improvement in fibrosis (RR 1.54, p = 0.24). There was a statistically significant increase in the overall adverse events (RR 1.10, p < 0.00001), while there was no significant difference in serious adverse events (p = 0.35). Conclusions: GLP-1 agonists improved liver fibrosis, steatohepatitis, weight loss, HbA1c, and liver enzymes in patients with MASLD or MASH. Overall, GLP-1 agonists were associated with a significantly higher risk of adverse events compared to the control, while serious adverse events were comparable between both groups. There was no significant effect on weight loss or improvement in fibrosis in patients without type 2 diabetes. However, there was a limited number of studies in this population. Thus, further research is needed before recommendations can be made for this subgroup. Full article

Background and Objectives: Chronic kidney disease (CKD) increases the risk of coronary artery disease (CAD), and vitamin D deficiency—particularly reduced levels of 1,25-dihydroxyvitamin D [1,25(OH)₂D], the biologically active form of vitamin D that declines early in CKD due to impaired renal conversion—may be a contributing factor. This study aimed to assess the relationship between 1,25(OH)₂D levels and the presence and severity of CAD in CKD patients. Materials and Methods: We retrospectively analyzed 398 non-dialysis CKD patients (eGFR < 60 mL/min/1.73 m²) who underwent elective coronary angiography. Serum 1,25(OH)₂D and 25(OH)D levels were measured, and CAD severity was assessed using the Gensini score. Results: Lower 1,25(OH)₂D levels were independently associated with both the presence and se-verity of CAD. Logistic regression revealed that each 1 pg/mL increase in 1,25(OH)₂D was linked to an 11% reduction in odds of significant CAD (OR: 0.89; 95% CI: 0.86–0.93; p < 0.001). In contrast, 25(OH)D was not significantly related to CAD. Linear regression showed an inverse correlation between 1,25(OH)₂D and Gensini scores (β = −0.329, p < 0.001), indicating reduced disease severity with higher vitamin D levels. Subgroup analyses confirmed consistent associations across age, sex, diabetes, hypertension, and LDL-cholesterol categories. ROC analysis demonstrated that 1,25(OH)₂D alone had good predictive ability for CAD (AUC = 0.818), which improved to 0.925 when combined with traditional risk factors. The optimal cutoff for 1,25(OH)₂D was ≤16.6 pg/mL, yielding 73.3% sensitivity and 83.5% specificity. Conclusions: Serum 1,25(OH)₂D is an independent predictor of both the presence and extent of CAD in CKD patients and may serve as a valuable non-traditional biomarker for cardiovascular risk assessment. Full article