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Background/Objectives: Protein intake is a key determinant of skeletal muscle health across the lifespan, yet optimal strategies must also account for cardiometabolic health and environmental sustainability. Differences in digestibility and amino acid composition between plant and animal-based proteins may influence their capacity to stimulate muscle protein synthesis (MPS), particularly in aging. Methods: This narrative review integrates evidence from acute tracer studies, randomized controlled trials, and long-term observational research comparing plant versus animal-based proteins for preserving muscle while supporting environmental goals and cardiometabolic health across populations. PubMed and Google Scholar were searched from inception to 11 December 2025 (plant-based protein OR animal-based protein AND sarcopenia OR muscle protein synthesis), with citation tracking. In total, 80 relevant findings were identified. Results: Acute tracer studies show that, gram-for-gram, animal-based proteins (particularly whey/dairy) stimulate greater myofibrillar protein synthesis due to higher leucine density, digestibility, and more rapid aminoacidemia—an effect that is more pronounced in older adults with anabolic resistance. In younger individuals, these differences are largely attenuated when total protein intake is sufficient. Importantly, the anabolic potential of plant-based proteins can be enhanced through higher dosing, amino acid or leucine fortification, and complementary protein blending (e.g., cereals with legumes or use of high-DIAAS isolates). Consistent with this, longer-term resistance training studies demonstrate comparable gains in muscle mass and strength between plant- and animal-based diets when protein intake (≥1.0–1.2 g/kg/day; ≥1.2–1.5 g/kg/day in illness), per-meal distribution (~0.4 g/kg with ~3–4 g leucine in older adults), and energy intake are optimized. Beyond muscle outcomes, higher plant-based protein intake is associated with favorable cardiometabolic profiles and lower environmental impact. Conclusions: An age-specific, mixed protein approach is recommended, emphasizing plant-based proteins in younger adults and higher-quality, leucine-rich proteins in older individuals. Defining optimal plant-to-animal-based protein ratios remains a key research priority.

Background Protein S (PS) is a cofactor of protein C (PC) which, when activated to activated PC (APC), mainly acts to degrade coagulation factor Va and VIIIa, and its deficiency may trigger an array of venous thromboembolic events (VTE); when unprovoked and life-threatening, these need indefinite anticoagulation. Direct oral anti coagulants (doac) are efficient drugs in therapy and prevention of VTE, although the optimal prophylactic doses in different conditions are not identified. Methods General characteristics and clinical events of 33 PS deficient patients (7 uneventful, 10 carrying also other thrombophilic conditions) were recorded from their medical records. Patients suffering from VTE underwent LMWH/Fondaparinux therapy followed by a full dose of doac (apixaban or rivaroxaban) and then a reduced dose doac (apixaban and rivaroxaban). Results Average, lowest and highest PS levels measured during follow-up were higher in male patients ( p  = 0.001). The cumulative prevalence of patients taking drugs acting on central nervous system (opioids, antidepressants, antiepileptic, antimigraine, antipsychotic) was 33%. Three minor hemorrhages were observed during the full-dose and one during the reduced doac therapy, while 3 VTE (1 pulmonary embolism and 2 deep venous thrombosis) occurred exclusively during the reduced-dose doac therapy ( p  = 0.033 Vs Full dose, 8.1 100patient/yr 95% CI 4–15). Compliance during the reduced-dose therapy was good according to the circulating levels of doac. In survival analysis, the only variable associated with VTE recurrence was PS deficiency combined with thrombophilic defects ( p  = 0.049). Conclusions Free PS deficiency affects the quality of life in many ways and a low dose doac in PS deficient patients is only partially effective in secondary prevention of VTE.

Hyperlipidemia is a major risk factor for cardiovascular morbidity and mortality. Statins are the first-choice therapy for dyslipidemias and are considered the cornerstone of atherosclerotic cardiovascular disease (ASCVD) in both primary and secondary prevention. Despite the statin-therapy-mediated positive effects on cardiovascular events, patient compliance is often poor. Statin-associated muscle symptoms (SAMS) are the most common side effect associated with treatment discontinuation. SAMS, which range from mild-to-moderate muscle pain, weakness, or fatigue to potentially life-threatening rhabdomyolysis, are reported by 10% to 25% of patients receiving statin therapy. There are many risk factors associated with patient features and hypolipidemic agents that seem to increase the risk of developing SAMS. Due to the lack of a “gold standard”, the diagnostic test for SAMS is based on a clinical criteria score, which is independent of creatine kinase (CK) elevation. Mechanisms that underlie the pathogenesis of SAMS remain almost unclear, though a high number of risk factors may increase the probability of myotoxicity induced by statin therapy. Some of these, related to pharmacokinetic properties of statins and to concomitant therapies or patient characteristics, may affect statin bioavailability and increase vulnerability to high-dose statins.

Background: The emergence of multidrug-resistant Gram-negative bacteria, particularly extended-spectrum β-lactamase (ESBL) and AmpC-producing Enterobacterales, has brought renewed interest in temocillin, a narrow-spectrum β-lactam antibiotic first introduced in the 1980s. Objectives: We aimed to provide a comprehensive overview of the microbiological, pharmacological, and clinical profile of temocillin. Methods: We conducted a narrative review of the literature using the PubMed database to identify relevant studies concerning the microbiology, pharmacokinetics, pharmacodynamics, clinical applications, and safety of temocillin. Results: Temocillin shows strong in vitro activity against ESBL- and AmpC-producing organisms, and partial efficacy against certain Klebsiella pneumoniae carbapenemase (KPC)-producing strains. Its pharmacokinetic and pharmacodynamic characteristics, including β-lactamase stability and low ecological impact, support its use in urinary tract infections, bloodstream infections, intra-abdominal infections, pneumonia, and central nervous system infections. Additionally, evidence supports its utility in outpatient parenteral antimicrobial therapy (OPAT), including subcutaneous administration, and in vulnerable populations such as pediatric, elderly, and immunocompromised patients. Temocillin demonstrates a favorable safety profile, minimal disruption of gut microbiota, and cost-effectiveness. It also exhibits synergistic activity with agents like fosfomycin, further enhancing its clinical value. Most of the current evidence is derived from retrospective and observational studies. Conclusions: Temocillin emerges as a promising carbapenem-sparing option for the treatment of challenging infections caused by multidrug-resistant Gram-negative bacteria.

Background: Fosfomycin, an old antibiotic attracting renewed interest, offers a broad spectrum of activity and unique synergy with other agents. While widely used in severe infections, real-world data on intravenous fosfomycin remain limited. Objectives: This study aimed to describe the clinical and microbiological characteristics of patients treated with intravenous fosfomycin and to analyze its administration modalities in a real-world setting. Methods: A multicenter retrospective cohort study was conducted across five Italian hospitals. Adult patients receiving intravenous fosfomycin between January 2020 and December 2023 were included. Results: We enrolled 393 patients. The median age was 69 years, with most patients (45%) admitted to Critical Care Units. Pneumonia (34%), bloodstream infections (22%), and urinary tract infections (21%) were the most common indications. Gram-negative bacteria, particularly E. coli and P. aeruginosa, were the predominant pathogens. Fosfomycin was used as empirical therapy in 55% of cases and was combined with other agents in almost all cases (99%). The most frequent partners were piperacillin/tazobactam (21%) and new beta-lactam/beta-lactamase inhibitor combinations (18%). The median treatment duration was seven days, with most subjects (65%) receiving a fosfomycin dosage regimen of 16 g/day. Minimum inhibitory concentrations (MICs) values for fosfomycin were available for 61 isolates (15%), with 78.7% (48/61) showing MIC ≤ 32 mg/L. C. difficile infection occurred in only 2% of patients. Mortality rates at 30, 60, and 90 days were 21.6%, 26.7%, and 29.3%, respectively. Conclusions: This study provides valuable insights into the real-world use of intravenous fosfomycin.

Cardiovascular disease (CVD) is still a leading cause of morbidity and mortality, despite all the progress achieved as regards to both prevention and treatment. Having high levels of lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease that operates independently. It can increase the risk of developing cardiovascular disease even when LDL cholesterol (LDL-C) levels are within the recommended range, which is referred to as residual cardiovascular risk. Lp(a) is an LDL-like particle present in human plasma, in which a large plasminogen-like glycoprotein, apolipoprotein(a) [Apo(a)], is covalently bound to Apo B100 via one disulfide bridge. Apo(a) contains one plasminogen-like kringle V structure, a variable number of plasminogen-like kringle IV structures (types 1–10), and one inactive protease region. There is a large inter-individual variation of plasma concentrations of Lp(a), mainly ascribable to genetic variants in the Lp(a) gene: in the general po-pulation, Lp(a) levels can range from <1 mg/dL to >1000 mg/dL. Concentrations also vary between different ethnicities. Lp(a) has been established as one of the risk factors that play an important role in the development of atherosclerotic plaque. Indeed, high concentrations of Lp(a) have been related to a greater risk of ischemic CVD, aortic valve stenosis, and heart failure. The threshold value has been set at 50 mg/dL, but the risk may increase already at levels above 30 mg/dL. Although there is a well-established and strong link between high Lp(a) levels and coronary as well as cerebrovascular disease, the evidence regarding incident peripheral arterial disease and carotid atherosclerosis is not as conclusive. Because lifestyle changes and standard lipid-lowering treatments, such as statins, niacin, and cholesteryl ester transfer protein inhibitors, are not highly effective in reducing Lp(a) levels, there is increased interest in developing new drugs that can address this issue. PCSK9 inhibitors seem to be capable of reducing Lp(a) levels by 25–30%. Mipomersen decreases Lp(a) levels by 25–40%, but its use is burdened with important side effects. At the current time, the most effective and tolerated treatment for patients with a high Lp(a) plasma level is apheresis, while antisense oligonucleotides, small interfering RNAs, and microRNAs, which reduce Lp(a) levels by targeting RNA molecules and regulating gene expression as well as protein production levels, are the most widely explored and promising perspectives. The aim of this review is to provide an update on the current state of the art with regard to Lp(a) pathophysiological mechanisms, focusing on the most effective strategies for lowering Lp(a), including new emerging alternative therapies. The purpose of this manuscript is to improve the management of hyperlipoproteinemia(a) in order to achieve better control of the residual cardiovascular risk, which remains unacceptably high.

Bempedoic acid is a new cholesterol-lowering drug, which has recently received US FDA and EMA approval. This drug targets lipid and glucose metabolism as well as inflammation via downregulation of ATP-citrate lyase and upregulation of AMP-activated protein kinase (AMPK). The primary effect is the reduction of cholesterol synthesis in the liver and its administration is generally not associated to unwanted muscle effects. Suppression of hepatic fatty acid synthesis leads to decreased triglycerides and, possibly, improved non-alcoholic fatty liver disease. Bempedoic acid may decrease gluconeogenesis leading to improved insulin sensitivity, glucose metabolism, and metabolic syndrome. The anti-inflammatory action of bempedoic acid is mainly achieved via activation of AMPK pathway in the immune cells, leading to decreased plasma levels of C-reactive protein. Effects of bempedoic acid on atherosclerotic cardiovascular disease, type 2 diabetes and chronic liver disease have been assessed in randomized clinical trials but require further confirmation. Safety clinical trials in phase III indicate that bempedoic acid administration is generally well-tolerated in combination with statins, ezetimibe, or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to achieve low-density lipoprotein cholesterol targets. The aim of this narrative review on bempedoic acid is to explore the underlying mechanisms of action and potential clinical targets, present existing evidence from clinical trials, and describe practical management of patients.

Myelosuppression is a common secondary manifestation of sepsis and is associated with increased morbidity and mortality. Recent evidence suggests that amino acid metabolism, particularly that of glutamic acid, may influence hematopoietic function and inflammatory responses 1 . Using a machine learning technique, we aimed to evaluate whether plasma amino acid levels at hospital admission are associated with myelosuppression and 30-day mortality in septic patients, with a focus on glutamic acid as a potential early biomarker. We conducted a prospective observational study on 390 adult patients hospitalized with sepsis at the University Hospital of Trieste. Patients were stratified into two groups on the basis of peripheral blood counts: myelosuppressed and non-myelosuppressed. Plasma levels of 13 amino acids were quantified at admission via high-performance liquid chromatography. Inflammatory markers, clinical outcomes, and 30-day mortality were recorded. Predictive models for myelosuppression were developed via Random Forest and interpreted via SHapley Additive exPlanations (SHAP) analysis. While nutritional intake and longitudinal amino acid trends were not available, we accounted for major comorbidities in the analysis. Myelosuppression was identified in 152 patients (39%) and was associated with significantly higher levels of inflammatory markers (e.g., C-reactive protein (CRP) and procalcitonin), an increased incidence of bacteremia, and increased 30-day mortality (20% vs. 12%, p = 0.03). Patients experiencing myelosuppression had lower median glutamic acid concentrations (134 vs. 154 µmol/L, p = 0.05). Among the 44 clinical and metabolic features, glutamic acid was the strongest predictor according to SHAP analysis. Furthermore, glutamic acid concentrations less than 134 µmol/L were associated with reduced survival according to Kaplan Meier analysis ( p = 0.013). Reduced plasma glutamic acid levels at admission are independently associated with myelosuppression and worse prognosis in septic patients. Although causality cannot be established and nutritional/temporal factors were not captured, glutamic acid may represent an early biomarker for risk stratification and deserves further investigation in longitudinal and interventional studies.

Insulin-like growth factor-binding protein-3 (IGFBP-3) plays a vital role in cellular growth, development, and survival. Incorporating IGFBP-3 into baseline prognostic evaluations may enhance the prediction of mortality in patients with sepsis. In this study, serum levels of IGFBP-3, C-reactive protein, procalcitonin, lactate, interleukin-6, and mid-regional pro-adrenomedullin were measured upon admission to the internal medicine unit (IMU) in 139 patients with microbiologically confirmed sepsis. The objectives were as follows: (1) to classify septic patient phenotypes based on optimal thresholds of independent prognostic biomarkers and (2) to evaluate whether these biomarkers improve the predictive accuracy of a clinical model (Model 1), which includes the clinical predictors of 1-year mortality. Age, sequential organ failure assessment (SOFA) score, multiple sources of infection, and IGFBP-3 levels independently predicted 1-year mortality. Patients with IGFBP-3 levels below 10.64 had significantly lower median body temperature (p = 0.008), reduced lymphocyte count (p = 0.001), and higher 1-year mortality (p < 0.001). Model 1 included age, SOFA score, and the presence of multiple sources of sepsis as predictor variables. Model 2 incorporated the same variables as Model 1, with the addition of IGFBP-3 levels. When comparing their prognostic performance, Model 2 demonstrated superior predictive accuracy for mortality at 60, 90, and 365 days following admission to the IMU. Low IGFBP-3 levels at IMU admission are strongly associated with worse outcomes in septic patients, supporting its potential use as a prognostic biomarker.

The glutathione system plays an essential role in antioxidant defense after surgery. We assessed the effects of intensive insulin treatment (IIT) on glutathione synthesis rate and redox balance in cancer patients, who had developed stress hyperglycemia after major surgery. We evaluated 10 non-diabetic cancer patients the day after radical abdominal surgery combined with intra-operative radiation therapy. In each patient, a 24-hr period of IIT, aimed at tight euglycemic control, was preceded, or followed, by a 24-hr period of conventional insulin treatment (CIT) (control regimen). Insulin was administered for 24 hours, during total parenteral nutrition, at a dosage to maintain a moderate hyperglycemia in CIT, and normoglycemic blood glucose levels in IIT (9.3±0.5 vs 6.5±0.3 mmol/L respectively, P<0.001; coefficient of variation, 9.7±1.4 and 10.5±1.1%, P = 0.43). No hypoglycemia (i.e., blood glucose < 3.9 mmol/L) was observed in any of the patients. Insulin treatments were performed on the first and second day after surgery, in randomized order, according to a crossover experimental design. Plasma concentrations of thiobarbituric acid reactive substances (TBARS) and erythrocyte glutathione synthesis rates (EGSR), measured by primed-constant infusion of L-[2H2]cysteine, were assessed at the end of each 24-hr period of either IIT or CIT. Compared to CIT, IIT was associated with higher EGSR (2.70±0.51 versus 1.18±0.29 mmol/L/day, p = 0.01) and lower (p = 0.04) plasma TBARS concentrations (2.2±0.2 versus 2.9±0.4 nmol/L). In patients developing stress hyperglycemia after major surgery, IIT, in absence of hypoglycemia, stimulates erythrocyte glutathione synthesis, while decreasing oxidative stress.