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Monomeric C-reactive protein (mCRP), once thought to be a figment of the imagination and whose biological activity was ascribed to its sodium azide preservative, has now pronounced itself as a critical molecule playing a direct role in mediating many of the acute and chronic aberrant pathological responses to inflammation. In this focused mini review, we describe the currently attributed pathobiological interactions of mCRP in disease, where its tissue and cellular distribution and deposition have recently been clearly characterized and linked to inflammation and other pathway-associated progression of neurological and cardiovascular complications and deleterious outcomes. and focus upon current opinions as to the diagnostic and prognostic potential of mCRP-plasma circulating protein and define the possible future therapeutics including ongoing research attempting to block CRP dissociation with small molecule inhibitors or prevention of cell surface binding directly using antibodies or modified orphan drug targeting directed towards CRP, inhibiting its cellular interactions and signaling activation. There is no doubt that understanding the full influence of the biological power of mCRP in disease development and outcome will be considered a critical parameter in future stratified treatment.

Regional anesthesia techniques such as the ultrasound-guided PECS II (pectoral nerve block) block are increasingly employed to optimize perioperative analgesia while minimizing systemic anesthetic exposure. Ropivacaine is commonly used for its favorable pharmacological profile; however, clinical data on its pharmacokinetics and systemic metabolite behavior following interpectoral administration remain limited. This study aimed to characterize the plasma concentration–time profile of ropivacaine and its main active metabolite, 3-OH-ropivacaine, in patients undergoing interpectoral nerve block, using a validated LC-MS/MS (liquid chromatography coupled with mass spectrometry) method. Venous blood samples were collected from 18 patients at predefined time points (0, 1, 3, 6, and 24 h) following a PECS II block performed with a ropivacaine-lidocaine mixture. Plasma concentrations were quantified via a validated LC-MS/MS protocol in accordance with FDA (Food and Drug Administration) and EMA (European Medicines Agency) guidelines. Pharmacokinetic parameters were derived using non-compartmental analysis. Ropivacaine reached a mean peak plasma concentration (Cmax—maximum concentration) of 167.5 ± 28.3 ng/mL at 1.3 ± 0.2 h (Tmax—maximum time). The metabolite 3-OH-ropivacaine peaked at 124.1 ± 21.4 ng/mL at 2.3 ± 0.3 h. The terminal elimination half-life was 19.4 ± 2.8 h for ropivacaine and 29.2 ± 3.1 h for its metabolite. Plasma levels demonstrated prolonged systemic exposure with predictable pharmacokinetics. The PECS II block using ropivacaine results in sustained systemic levels of both the parent drug and its primary metabolite, supporting its role in prolonged perioperative analgesia. These data provide a pharmacokinetic foundation for personalized regional anesthesia protocols. This strategy facilitates the adaptation of anesthetic protocols to the individual characteristics of each patient, aligning with the principles of personalized medicine, particularly in patients with altered metabolic capacity.

Background The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) of TNF-α gene are associated with sepsis in terms of risk, severity and outcome. Methods We performed a prospective study on 163 adult critically ill septic patients (septic shock 65, sepsis 98, further divided in 40 survivors and 123 deceased) and 232 healthy controls. Genotyping of TNF-α SNPs (-308G/A, -238G/A, -376G/A and +489G/A) was performed for all patients and controls and plasma cytokine levels were measured during the first 24 h after sepsis onset. Results TNF-α  +489G/A A-allele carriage was associated with significantly lower risk of developing sepsis and sepsis shock (AA+AG vs GG: OR = 0.53; p  = 0.004; 95% CI = 0.34–0.82 and OR = 0.39; p  = 0.003; 95% CI = 0.21–0.74, respectively) but not with sepsis-related outcomes. There was no significant association between any of the other TNF-α promoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-α levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-α levels in septic shock. Conclusions TNF-α  +489G/A SNP A-allele carriage may confer protection against sepsis and septic shock development but apparently does not influence sepsis-related mortality. Promoter TNF-α SNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes.

Biomaterials and biomedical devices interact with the human body at different levels. At one end of the spectrum, medical devices in contact with tissue pose risks depending on whether they are deployed on the skin or implanted. On the other hand, food packaging and associated material technologies must also be biocompatible to prevent the transfer of harmful molecules and contamination of food, which could impact human health. These seemingly unlinked domains converge into a shared need for the elaboration of new laboratory evaluation protocols that consider recent advances in biomaterials and biodevices, coupled with increasing legal restrictions on the use of animal models. Here, we aim to select and prescribe physiologically relevant microenvironment conditions for biocompatibility testing of novel biomaterials and biodevices. Our discussion spans (1) the development of testing protocols according to material classes, (2) current legislation and standards, and (3) the preparation of biomimetic setups that replicate the microenvironment, with a focus on the multidisciplinary dimension of such studies. Testing spans several characterization domains, beginning with chemical properties, followed by mechanical integrity and, finally, biological response. Biomimetic testing conditions typically include temperature fluctuations, humidity, mechanical stress and loading, exposure to body fluids, and interaction with multifaceted biological systems.

Background/Objectives: Nutrition at the end of life raises many dilemmas. “End of life” refers to the period associated with a progressive incurable disease, with a life expectancy of less than six months, and limited curative treatments. In intensive care units (ICUs), decisions about artificial nutrition and hydration (clinically assisted nutrition and hydration, CANH) are especially complex because patient goals shift from survival to comfort. Nutrition and hydration are often requested by patients and their families, even when clinical benefits are uncertain. This article aims to provide a multidimensional analysis of the pathophysiological, clinical, ethical and legal considerations of nutritional support in the final stages of life. Methods: We conducted a narrative review of the literature published between January 2000 and June 2025 by searching the PubMed/MEDLINE, Web of Science, and Scopus databases and included original articles, clinical trials, reviews, international guidelines, and public policy documents involving adult population at the end of life. The narrative approach enabled the multidimensional integration of the collected data. Results: Terminally ill patients often develop anorexia and cachexia leading to irreversible muscle loss and resistance to nutritional support. CANH (enteral or parenteral) has limited success and carries increased risks. In advanced cancer and dementia, studies do not show clear benefits for survival or quality of life. Nutritional counseling and oral supplements may help alleviate symptoms, but manual feeding remains the standard of care in the terminal stages. In ICU settings, starting or maintaining CANH demands careful evaluation of goals, prognosis, and burdens. Cultural legal differences and approaches between countries also influence clinical practice and family expectations. Conclusions: CANH at the end of life should be viewed as a medical intervention that requires both scientific and ethical justification. The decision to initiate or discontinue it should be individualized. Clear and empathetic communication between the medical team, patient, and family is essential to avoid inappropriate decisions.

Sepsis is a major medical emergency, characterized by a dysfunctional immune response to infection, which often progresses to multiple organ failure and death. Early diagnosis and prognostic evaluation present significant challenges due to limitations in the specificity and sensitivity of traditional biomarkers. This narrative review summarizes recent evidence on the potential of circulating microRNAs (miRNAs) such as miR-150, miR-146a, miR-223, miR-155, miR-122, and miR-4772-5p and plasma gelsolin (pGSN) as diagnostic and prognostic markers in sepsis. We discuss mechanisms involved and their potential for integration with artificial intelligence (AI) in personalized medicine. PubMed, Embase, and Web of Science databases were searched for relevant literature. Original research, systematic reviews, and meta-analyses focused on the diagnostic or prognostic value of circulating miRNAs or pGSN in sepsis were included; opinion papers and case reports were excluded. Altered expression of certain circulating microRNAs correlates with disease severity and mortality. Among circulating microRNAs (miRNAs), miR-122 and miR-150 have become the most consistently validated biomarkers in clinical studies, associated with sepsis severity and death rates. Additionally, other miRNAs such as miR-146a, miR-155, and miR-223 play roles in modulating immune and endothelial responses, highlighting the complex regulation of sepsis pathophysiology. Low pGSN concentrations at admission are associated with severe sepsis and acute respiratory distress syndrome, and serve as an independent predictor of mortality. Preclinical studies suggest that supplementation with exogenous pGSN could increase survival. AI algorithms show promising results for early sepsis detection and optimization of therapeutic decisions. However, combining circulating miRNAs and plasma gelsolin (pGSN) into AI-based models is still an exploratory idea that needs prospective validation, assay standardization, and multicenter studies before it can be used clinically.

Background/Objectives: The clinical forms of coronavirus disease 2019 (COVID-19) vary widely in severity, ranging from asymptomatic or moderate cases to severe pneumonia that can lead to acute respiratory failure, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Our main objective was to determine the prevalence of bacterial and fungal secondary infections in an intensive care unit (ICU). Secondary objectives included analyzing the impact of these infections on mortality and medical resource utilization, as well as assessing antimicrobial resistance in this context. Methods: We conducted a retrospective cohort study that included critically ill severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients treated in an ICU and analyzed the prevalence of co-infections and superinfections. Results: A multivariate analysis of mortality found that the presence of superinfections increased the odds of death by more than 15-fold, while the Sequential Organ Failure Assessment (SOFA) score and C-reactive protein (adjusted for confounders) increased the odds of mortality by 51% and 13%, respectively. The antibiotic resistance profile of microorganisms indicated a high prevalence of resistant strains. Carbapenems, glycopeptides, and oxazolidinones were the most frequently used classes of antibiotics. Among patients, 27.9% received a single antibiotic, 47.5% received two from different classes, and 24.4% were treated with three or more. Conclusions: The incidence and spectrum of bacterial and fungal superinfections are higher in critically ill ICU patients, leading to worse outcomes in COVID-19 cases. Multidrug-resistant pathogens present significant challenges for ICU and public health settings. Early screening, accurate diagnosis, and minimal use of invasive devices are essential to reduce risks and improve patient outcomes.

Introduction: Critically ill patients in intensive care units (ICUs) are at high risk of malnutrition, which can result in muscle atrophy, polyneuropathy, increased mortality, or prolonged hospitalizations with complications and higher costs during the recovery period. They often develop ICU-acquired weakness, exacerbated by sepsis, immobilization, and drug treatments, leading to rapid muscle mass loss and long-term complications. Studies indicate that adequate protein and calorie intake can decrease mortality and improve prognosis and recovery. However, optimal implementation remains a critical challenge. Objectives: This narrative review aims to summarize recent advances in nutritional strategies for critically ill patients. It highlights the benefits and limitations of current approaches including enteral (EN) and parenteral nutrition (PN) and examines their impact on clinical outcomes and overall mortality. Additionally, the review explores the emerging role of precision nutrition in critical care using technologies such as metabolomics and artificial intelligence (AI) to provide valuable insights into optimizing nutritional care in critically ill patients. Methods: A comprehensive literature search was conducted to identify recent studies, clinical guidelines, and expert consensus papers on nutritional support for ICU patients. The investigation focused on critical aspects such as the optimal timing for intervention, the route of administration, specific protein and energy targets, and technological innovations to support personalized nutrition, ensuring that each patient receives tailored support based on their unique needs. Results: Guidelines recommend initiating EN or PN nutrition within the first 48 h of admission, using indirect calorimetry (IC) to estimate energy needs, and supplementing protein up to 1.2 g/kg/day after stabilization. IC has gained importance in assessing energy needs but is still underused in the ICU. EN is preferred because it maintains intestinal integrity, reduces the risk of infections, and is recommended within the first 48 h of ICU admission. PN is used when EN is infeasible, but it increases the risk of infection. By integrating metabolomics with transcriptomic and genomic data, we can gain a deeper understanding of the effect of nutrition on cellular homeostasis, facilitating personalized treatments and enhancing the recovery of critically ill patients. Conclusions: AI is becoming increasingly important in monitoring and evaluating artificial nutrition, providing a more accurate and efficient alternative to traditional methods. AI can assist in identifying and managing malnutrition and is effective for estimating caloric and nutrient intake. AI minimizes human error, enables continuous monitoring, and integrates various data sources. The nutritional care of critically ill patients requires collaboration among specialists from diverse fields, including physicians, nutritionists, pharmacists, radiologists, IT experts, and policymakers.

Background/Objectives: Sepsis is characterized by a dysregulated host response to infection, where immune-inflammatory and thrombo-inflammation drive organ dysfunction. Early recognition of high-risk patients is essential. In addition, the increasing prevalence of multidrug-resistant (MDR) pathogens complicates therapeutic strategies, as delays in appropriate antimicrobial therapy are strongly associated with poor outcomes. Methods: We conducted a retrospective, single-center cohort study including 120 critically ill patients fulfilling Sepsis-3 criteria. Demographic, clinical, and laboratory data were collected at intensive care unit (ICU) admission, 48 h, and 72 h. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated from complete blood counts. At the same time, the Carmeli score was used as a surrogate for MDR infection risk. Prognostic accuracy was assessed using ROC curve analysis and multivariable logistic regression. Results: Persistently elevated NLR at 72 h and a delayed decline in platelet counts were associated with higher mortality. NLR at 72 h showed good predictive accuracy (AUC = 0.765; 95% CI 0.668–0.863), and the combination of APACHE II and NLR improved prognostic performance (AUC = 0.827). Importantly, the Carmeli score, reflecting MDR infection risk, was an independent predictor of outcome, linking antimicrobial resistance risk with sepsis prognosis. Conclusions: Dynamic immune-inflammatory biomarkers (NLR, platelets), when integrated with MDR risk assessment through the Carmeli score, provide a simple and cost-effective strategy for early prognostic stratification in sepsis. This combined approach may help facilitate early therapeutic decisions and patient care triage.

Knowledge of drug pharmacokinetics and tissue distribution is precious for ensuring patient safety and optimizing treatments. The varied use of local anesthetics, as well as the fact that anesthetics can sometimes have low therapeutic indices and numerous adverse drug reactions, makes any novel pharmacokinetics information valuable. The present manuscript describes a pharmacokinetic study of ropivacaine carried out after plane block anesthesia on an animal model, using high sensitivity, accurate, and precise LC-MS/MS bioanalysis. Both plasmatic concentrations and tissue distribution of ropivacaine and its primary active metabolite were determined. The results showed a tissue affinity of the anesthetics, a clearance of ropivacaine mainly by hepatic metabolism, and the final, mainly renal excretion of the hydroxylated metabolite. While the results cannot simply and directly be transposed to human pharmacokinetics, they offer a valuable basis for future studies and can contribute to a better understanding of the bioavailability and toxicology of the widely used modern anesthetic.