Search Results (1,818)

Sex-based immunological differences significantly influence the outcome of vaccination, yet the molecular mediators underpinning these differences remain largely elusive. MicroRNAs (miRNAs), key post-transcriptional regulators of gene expression, have emerged as critical modulators of innate and adaptive immune responses. In this study, we investigated the expression profile of selected circulating miRNAs as potential biomarkers of sex-specific humoral responses to the mRNA COVID-19 vaccine in a cohort of health care workers. Plasma samples were collected longitudinally at a defined time point (average 71 days) post-vaccination and analyzed using RT-qPCR to quantify a panel of immune-relevant miRNAs. Anti-spike (anti-S) IgG titers were measured by chemiluminescent immunoassays. Our results revealed sex-dependent differences in miRNA expression dynamics, with miR-221-3p and miR-148a-3p significantly overexpressed in vaccinated female HCWs and miR-155-5p overexpressed in vaccinated males. MiR-148a-3p showed a significant association with anti-S/RBD (RBD: receptor binding domain) IgG levels in a sex-specific manner. Bioinformatic analysis for miRNA targets indicated distinct regulatory networks and pathways involved in innate and adaptive immune responses, potentially underlying the differential immune activation observed between males and females. These findings support the utility of circulating miRNAs as minimally invasive biomarkers for monitoring and predicting sex-specific vaccine-induced immune responses and provide mechanistic insights that may inform tailored vaccination strategies. Full article

Vitamin D has emerged as a modulatory factor in the pathogenesis and management of diabetes mellitus due to its influence on pancreatic β-cell function, immune regulation, and inflammatory pathways. This narrative review critically examines mechanistic and clinical evidence linking vitamin D status with type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes (GDM). In T1DM, vitamin D’s immunomodulatory effects are thought to protect β-cells from autoimmune destruction; epidemiological studies associate vitamin D sufficiency with lower T1DM incidence and improved glycemic control, although causality remains under investigation. In T2DM, vitamin D deficiency is associated with worsened metabolic control and may contribute to disease development in at-risk individuals; however, it does not influence the initial onset of T2DM in patients who are already diagnosed. Intervention trials indicate that correcting the deficiency can modestly improve insulin sensitivity, β-cell function, and metabolic parameters. GDM has similarly been linked to hypovitaminosis D, with low maternal vitamin D levels associated with higher GDM risk and adverse perinatal outcomes; mechanistic insights suggest that adequate vitamin D supports glucose homeostasis in pregnancy, and emerging trials demonstrate improved insulin resistance with maternal vitamin D supplementation. Across these diabetes subtypes, maintaining sufficient vitamin D levels appears to confer metabolic benefits and may serve as an adjunct to current preventive and therapeutic strategies. However, definitive evidence from large-scale trials is required to establish optimal vitamin D supplementation protocols and confirm its efficacy in diabetes care. Full article

Cardiovascular diseases (CVDs) are the leading global cause of death, with long-term hospitalization becoming increasingly frequent in advanced or chronic cases. In this context, the interplay between systemic factors such as lipid metabolism, circulating metabolites, gut microbiota, and oral health is gaining attention for its potential role in influencing inflammation, cardiometabolic risk, and long-term outcomes. Despite their apparent independence, these domains are increasingly recognized as interconnected and influential in cardiovascular pathophysiology. Methods: This narrative review was conducted by analyzing studies published between 2015 and 2024 from databases including PubMed, Scopus, and Web of Science. Keywords such as “lipid profile,” “metabolomics,” “gut microbiota,” “oral health,” and “cardiovascular disease” were used. Original research, meta-analyses, and reviews relevant to hospitalized cardiac patients were included. A critical integrative approach was applied to highlight cross-domain connections. Results and Discussion: Evidence reveals significant interrelations between altered lipid profiles, gut dysbiosis (including increased TMAO levels), metabolic imbalances, and oral inflammation. Each component contributes to a systemic pro-inflammatory state that worsens cardiovascular prognosis, particularly in long-term hospitalized patients. Despite isolated research in each domain, there is a paucity of studies integrating all four. The need for interdisciplinary diagnostic models and preventive strategies is emphasized, especially in populations with frailty or immobilization. Conclusions: Monitoring lipid metabolism, metabolomic shifts, gut microbial balance, and oral status should be considered part of comprehensive cardiovascular care. Gut microbiota exerts a dual role in cardiac health: when balanced, it supports anti-inflammatory and metabolic homeostasis; when dysbiotic, it contributes to systemic inflammation and worsened cardiac outcomes. Future research should aim to develop integrative screening tools and personalized interventions that address the multifactorial burden of disease. A systemic approach may improve both short- and long-term outcomes in this complex and vulnerable patient population. Full article

Background: Fluid management is a critical aspect of care for neurocritically ill patients, yet the optimal approach remains unclear. The relationship between fluid balance and clinical outcomes in these patients requires further investigation, particularly regarding the timing and volume of fluid administration. Methods: This retrospective observational study analyzed 2186 adult patients admitted to the neurosurgical intensive care unit (ICU) from January 2013 to December 2022. We employed a generalized additive model (GAM) with cubic spline smoothing to examine non-linear relationships between fluid balance and mortality. The maximally selected rank statistics method was used to determine the optimal cutoff value for fluid balance. Associations between fluid balance patterns and 28-day mortality were analyzed using a multivariable logistic regression model. Results: Initial analysis identified fluid balance on day 1 as the most significant predictor of mortality; patients with positive fluid balance showed a higher 28-day mortality. Non-survivors showed significantly higher fluid input throughout the 7-day observation period, particularly during the first 24 h (4444 mL vs. 3978 mL, p = 0.007). Multivariable analysis confirmed that fluid balance on day 1 remained independently associated with 28-day mortality after adjusting for confounders (adjusted odd ratio 1.705, 95% confidence interval: 1.001–2.905, p = 0.049). Additionally, the relationship between fluid input day 1 and mortality demonstrated a progressively increasing probability of 28-day mortality with higher fluid volumes. Early fluid balance, particularly during the first 24 h of ICU admission, shows a significant association with mortality in neurocritically ill patients. Conclusions: These findings emphasize the crucial importance of careful fluid management in the early phase of neurocritical care and suggest that implementation of strict fluid monitoring protocols, especially during the initial period of care, may improve patient outcomes. Full article

Ceftazidime–avibactam (CAZ-AVI) is a second-generation intravenous β-lactam/β-lactamase inhibitor combination. In recent years, substantial evidence has emerged regarding the efficacy and safety of CAZ-AVI. However, data on its use in critically ill patients remain limited. Background/Objectives: This multicenter, retrospective, observational cohort study was conducted across four Intensive Care Units (ICUs) in three hospitals in the Marche region of Italy. The primary objective was to evaluate the 30-day clinical outcomes and identify risk factors associated with 30-day clinical failure—defined as death, microbiological recurrence, or persistence within 30 days after discontinuation of therapy—in critically ill patients treated with CAZ-AVI. Methods: The study included all adult critically ill patients admitted to the participating ICUs between January 2020 and September 2023 who received CAZ-AVI for at least 72 h for the treatment of a confirmed or suspected Gram-negative bacterial (GNB) infection. Results: Among the 161 patients included in the study, CAZ-AVI treatment resulted in a positive clinical outcome (i.e., clinical improvement and 30-day survival) in 58% of cases (n = 93/161), while the overall mortality rate was 24% (n = 38/161). Relapse or persistent infection occurred in a substantial proportion of patients (25%, n = 41/161). Notably, acquired resistance to CAZ-AVI was observed in 26% of these cases, likely due to suboptimal use of the drug in relation to its pharmacokinetic/pharmacodynamic (PK/PD) properties in critically ill patients. Furthermore, treatment failure was more frequent among immunosuppressed individuals, particularly liver transplant recipients. Conclusions: This study demonstrates that the mortality rate among ICU patients treated with this novel antimicrobial combination is consistent with findings from other studies involving heterogeneous populations. However, the rapid emergence of resistance underscores the need for vigilant surveillance and the implementation of robust antimicrobial stewardship strategies. Full article

Background: The progression of Alzheimer’s Disease (AD) deeply affects not only the diagnosed person but also their close relatives, who are often called to take on the role of informal caregivers. This transition is frequently unplanned and emotionally complex, yet poorly understood in its deeper processual dimensions. This study aims to explore and theorize the transition experienced by a family member becoming the primary informal caregiver for a person with advanced AD. Methods: A qualitative study based on the Constructivist Grounded Theory according to Charmaz’s approach (2006) was conducted. In-depth interviews were carried out with 10 participants who had become informal caregivers for a loved one with advanced AD. Data were analyzed using initial coding, focused coding, the constant comparative method, and theoretical coding. Results: Ten caregivers (mean age 39 years, range 35–54; nine females) of patients with advanced AD participated in the study. The analysis revealed a complex, emotionally intense caregiving experience marked by sacrifice, feelings of powerlessness, identity loss, and the necessity of sharing caregiving responsibilities. A core category emerged: A Silent and Certain Willingness to Care, representing the caregivers’ deep, often unconscious commitment to prioritize the care of their loved ones above their own needs. Four interconnected phases characterized the caregiving process: (1) The Changing Daily Life—involving significant sacrifices in personal and social life; (2) Feeling Powerless—confronting the inevitable decline without means to alter the course; (3) Losing Oneself—experiencing physical and psychological exhaustion and a sense of identity loss; and (4) Sharing with Others—seeking external support to sustain caregiving. These findings highlight the evolving nature of becoming a caregiver and the enduring dedication that sustains this role despite the challenges. Conclusions: The progression of AD deeply transforms the lives of caregivers, who become co-sufferers and active participants in the disease’s management. The results underscore the urgency of designing integrative care strategies—including psychological, social, and potentially technological support—that can enhance both patient outcomes and caregiver resilience. Grounded in real-world experiences, this study contributes to the broader neurodegeneration discourse by emphasizing caregiving as a critical factor in long-term disease management and therapeutic success. Full article

Background: Pain is a problem faced by critically ill surgical patients and has a major impact on their outcomes. Pain assessment is therefore essential for effective pain management, with a combination of pharmacological and non-pharmacological treatment. Clinical supervision, supported by models such as SafeCare, can improve professional development, safety and the quality of care in intensive care units. Objectives: This study aimed to: (1) assess current pain assessment practices in a polyvalent Intensive Care Unit (ICU) in the Porto district; (2) identify nurses’ training needs regarding the Clinical Supervision-Sensitive Indicator—Pain; and (3) evaluate the impact of clinical supervision sessions on pain assessment practices. Methods: A quantitative, quasi-experimental, cross-sectional study with a pre- and post-intervention design was conducted. Based on the SafeCare model, it included a situational diagnosis, 6 clinical supervision sessions (February 2023), and outcome evaluation via nursing record audits (November 2022 and May 2023) in 31 total critical ill patients. Pain was assessed using standardised tools, in line with institutional protocols. Data was analysed using Software Statistical Package for the Social Sciences v25.0. Results: Pain was highly prevalent in the first 24 h, decreasing during hospitalisation. Generalised acute abdominal pain predominated, with mild to moderate intensity, and was exacerbated by wound care and mobilisation/positioning. Pain management combined pharmacological and non-pharmacological treatment. There was an improvement in all the parameters of the pain indicator post-intervention. Conclusions: Despite routine assessments, gaps remained in reassessing pain post-analgesia and during invasive procedures. Targeted clinical supervision and ongoing training proved effective in improving compliance with protocols and supporting safer, more consistent pain management. Full article

Background/Objectives: Wilson’s disease (WD) is a rare autosomal recessive disorder of copper metabolism that results in hepatic, neurological, and psychiatric manifestations. Despite being described globally, data from the Middle East remains limited. This study presents the first comprehensive national cohort analysis of WD in Oman, examining clinical features, diagnostic challenges, treatment patterns, and long-term outcomes. Methods: A retrospective cohort study was conducted on 36 Omani patients diagnosed with WD between 2013 and 2020 at Sultan Qaboos University Hospital using AASLD diagnostic criteria. Clinical presentation, biochemical parameters, treatment regimens, and progression-free survival were analyzed. Results: The median age at diagnosis was 14.5 years, with a slight female predominance (55.6%). Clinical presentation varied: 25% had hepatic symptoms, 22.2% had mixed hepatic-neurological features, and 16.7% presented with neurological symptoms alone. Asymptomatic cases identified via family screening accounted for 33.3%. Diagnostic delays were most pronounced among patients presenting with neurological symptoms. A positive family history was reported in 88.9% of cases, suggesting strong familial clustering despite a low rate of consanguinity (5.6%). Regional distribution was concentrated in Ash Sharqiyah North and Muscat. Chelation therapy with trientine or penicillamine, often combined with zinc, was the mainstay of treatment. Treatment adherence was significantly associated with improved progression-free survival (p = 0.012). Conclusions: WD in Oman is marked by heterogeneous presentations, frequent diagnostic delays, and strong familial clustering. Early detection through cascade screening and sustained treatment adherence are critical for favorable outcomes. These findings support the need for national screening policies and structured long-term care models for WD in the region. Full article

A global poly-crisis of climate change, biodiversity loss, dwindling natural resources, geopolitical instability, among other complex challenges, is on the rise. Societal transformations are therefore imminent, whether intended or unintended. The key question is how to steward and facilitate such changes where fragmentation and siloed ways of working persist. The concept of synergies and the notion of synergic action could help overcome fragmented efforts to steer transformative changes. However, there exists a critical research gap in understanding the conditions needed to enable synergic action. This paper thus explores how synergic action is currently undertaken and the key essentials needed to deliver synergic action. The study uses a case study of the Yorkshire food system transformation to learn from its exemplar practitioners. The study used semi-structured interviews and a thematic analysis process to reach our two key findings. First, we highlight the three types of synergic action: (1) Non-systemic synergic action, (2) Non-systemic synergic action with multiple outcomes, and (3) Systemic synergic action. Differentiating types of synergic action can help identify where synergic action is already underway and guide more explicit efforts towards transformative change. The second key finding is the five essentials for synergic action, which are (1) leadership for synergic action; (2) networking, partnerships, and collaborations; (3) care and understanding; (4) a systems approach; and (5) intentionality for synergic action. This study brings to the fore the importance of intentionality, without which the first four essentials are less likely to coalesce. This is important to inform the reflection and learning of practitioners of systemic change about how they are currently and could be working more synergistically in the future, driven by clear intentionality. Full article

Introduction: Renal malacoplakia is a rare chronic granulomatous disease, often associated with immunosuppression and persistent Gram-negative infections, particularly Escherichia coli. Case Presentation: We present a case involving a 31-year-old woman with hypertension, gestational diabetes, and prior uterine curettage after labor induction for preeclampsia at 23 weeks. She developed urinary sepsis post-procedure. Imaging revealed bilateral nephromegaly, while laboratory tests showed acute kidney injury (KDIGO stage III), anemia, and thrombocytopenia. Blood and urine cultures grew Escherichia coli. Renal biopsy confirmed malacoplakia, demonstrating PAS-positive Michaelis–Gutmann bodies and Von Hansemann cells. The patient responded to prolonged antibiotic therapy and supportive care. Discussion and Conclusion: This case highlights the importance of considering renal malacoplakia in patients with atypical urinary tract infections and nephromegaly, particularly in obstetric settings. Histopathological confirmation is essential, and timely treatment with intracellularly active antibiotics can lead to favorable outcomes. Early diagnosis is critical to prevent irreversible renal damage. Full article

Background: Accurate and timely prediction of mortality in intensive care unit (ICU) patients, particularly those with COVID-19, remains clinically challenging due to complex immune responses. Proteomic cytokine profiling holds promise for refining mortality risk assessment. Methods: Serum samples from 89 ICU patients (55 discharged, 34 deceased) were analyzed using a multiplex 21-cytokine panel. Samples were stratified into three groups based on time from collection to outcome: ≤48 h (Group 1: Early), >48 h to ≤7 days (Group 2: Intermediate), and >7 days to ≤14 days (Group 3: Late). Cytokine levels, simple cytokine ratios, and previously unexplored complex ratios between pro- and anti-inflammatory cytokines were evaluated. Machine learning-based feature selection identified the most predictive ratios, with performance evaluated by area under the curve (AUC), sensitivity, and specificity. Results: Complex cytokine ratios demonstrated superior predictive accuracy compared to traditional severity markers (APACHE II, SAPS II, SOFA), individual cytokines, and simple ratios, effectively distinguishing discharged from deceased patients across all groups (AUC: 0.918–1.000; sensitivity: 0.826–1.000; specificity: 0.775–0.900). Conclusions: Multiplex cytokine profiling enhanced by computationally derived complex ratios may offer robust predictive capabilities for ICU mortality risk stratification, serving as a valuable tool for personalized prognosis in critical care. Full article

Background/Objectives: Evidence-based nursing practice (EBNP) is essential in high-acuity settings such as intensive care units (ICUs) and emergency departments (EDs), where nurses are frequently required to make time-critical, high-stakes clinical decisions that directly influence patient safety and outcomes. Despite its recognized importance, the implementation of EBNP remains inconsistent, with frontline nurses often facing barriers to accessing and applying current evidence. Methods: This descriptive, cross-sectional study systematically mapped and prioritized clinical questions generated by ICU and ED nurses at a tertiary hospital in South Korea. Using open-ended questionnaires, 204 clinical questions were collected from 112 nurses. Each question was coded and classified according to the Nursing Interventions Classification (NIC) taxonomy (8th edition) through a structured cross-mapping methodology. Inter-rater reliability was assessed using Cohen’s kappa coefficient. Results: The majority of clinical questions (56.9%) were mapped to the Physiological: Complex domain, with infection control, ventilator management, and tissue perfusion management identified as the most frequent areas of inquiry. Patient safety was the second most common domain (21.6%). Notably, no clinical questions were mapped to the Family or Community domains, highlighting a gap in holistic and transitional care considerations. The mapping process demonstrated high inter-rater reliability (κ = 0.85, 95% CI: 0.80–0.89). Conclusions: Frontline nurses in high-acuity environments predominantly seek evidence related to complex physiological interventions and patient safety, while holistic and community-oriented care remain underrepresented in clinical inquiry. Utilizing the NIC taxonomy for systematic mapping establishes a reliable framework to identify evidence gaps and support targeted interventions in nursing practice. Regular protocol evaluation, alignment of continuing education with empirically identified priorities, and the integration of concise evidence summaries into clinical workflows are recommended to enhance EBNP implementation. Future research should expand to multicenter and interdisciplinary settings, incorporate advanced technologies such as artificial intelligence for automated mapping, and assess the long-term impact of evidence-based interventions on patient outcomes. Full article

Introduction: Cystic fibrosis (CF) is a genetic condition affecting several organs and systems, including the pancreas, colon, respiratory system, and reproductive system. The detection of a growing number of CFTR variants and genotypes has contributed to an increase in the CF population which, in turn, has had an impact on the overall statistics regarding the prognosis and outcome of the condition. Given the increase in life expectancy, it is critical to better predict outcomes and prognosticate in CF. Thus, each person’s choice to aggressively treat specific disease components can be more appropriate and tailored, further increasing survival. The objective of our narrative review is to summarize the most recent information concerning the value and significance of clinical parameters in predicting outcomes, such as gender, diabetes, liver and pancreatic status, lung function, radiography, bacteriology, and blood and sputum biomarkers of inflammation and disease, and how variations in these parameters affect prognosis from the prenatal stage to maturity. Materials and methods: A methodological search of the available data was performed with regard to prognostic factors in the evolution of CF in children and young adults. We evaluated articles from the PubMed academic search engine using the following search terms: prognostic factors AND children AND cystic fibrosis OR mucoviscidosis. Results: We found that it is crucial to customize CF patients’ care based on their unique clinical and biological parameters, genetics, and related comorbidities. Conclusions: The predictive significance of more dynamic clinical condition markers provides more realistic future objectives to center treatment and targets for each patient. Over the past ten years, improvements in care, diagnostics, and treatment have impacted the prognosis for CF. Although genotyping offers a way to categorize CF to direct research and treatment, it is crucial to understand that a variety of other factors, such as epigenetics, genetic modifiers, environmental factors, and socioeconomic status, can affect CF outcomes. The long-term management of this complicated multisystem condition has been made easier for patients, their families, and physicians by earlier and more accurate identification techniques, evidence-based research, and centralized expert multidisciplinary care. Full article

Schizophrenia (SCZ) is a debilitating disorder with substantial societal and economic impacts. The clinical high risk of psychosis (CHR-P) state generally precedes the onset of SCZ, offering a window for early intervention. However, treatment guidelines for CHR-P individuals remain contentious, particularly regarding antipsychotic (AP) medications. Although several studies have examined the effects of APs on reducing the risk of conversion to psychosis, the novelty of this narrative review lies in its focus on differentiating APs’ effects on positive and negative symptoms, as well as cognitive functioning, in CHR-P individuals. Evidence suggests that APs may be cautiously recommended for attenuated positive symptoms to stabilize individuals for psychological interventions, but their use in treating negative symptoms is generally discouraged due to limited efficacy and potential side effects. Similarly, the effects of APs on cognitive abilities remain underexplored, with results indicating a lack of significant neurocognitive outcomes. In conclusion, APs’ use in CHR-P patients requires careful consideration due to limited evidence and potential adverse effects. Future research should focus on individual symptom domains and treatment modalities to optimize outcomes in this critical population. Until then, a cautious approach emphasizing non-pharmacological interventions is advisable. Full article

Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical public health threat due to its rapid nosocomial dissemination, limited therapeutic options, and elevated mortality rates. This study aimed to characterize the epidemiology, carbapenemase profiles, and antimicrobial susceptibility patterns of CRKP isolates, as well as the clinical features and outcomes observed in infected or colonized patients. Materials and Methods: We conducted a retrospective analysis of clinical and microbiological data from patients with CRKP infections or colonization admitted between January 2023 and January 2024. Descriptive statistics were used to assess prevalence, resistance patterns, and patient outcomes. Two binary logistic regression models were applied to identify independent predictors of sepsis and in-hospital mortality. Results: Among 89 CRKP isolates, 45 underwent carbapenemase typing. More than half were metallo-β-lactamase (MBL) producers, with 44.4% co-harbouring NDM and OXA-48-like enzymes. Surgical intervention was associated with a significantly lower risk of sepsis (p < 0.01) and in-hospital mortality (p = 0.045), whereas intensive care unit (ICU) stay was a strong predictor of both outcomes. ICU admission conferred a 10-fold higher risk of sepsis (95%Cl 2.4–41.0) and a 40.8-fold higher risk of in-hospital death (95% Cl 3.5–473.3). Limitations: This single-center retrospective study included a limited number of isolates in certain groups. Additionally, cefiderocol (FDC) susceptibility was assessed by disk diffusion rather than by the broth microdilution method. Conclusions: Our study underscores the increasing prevalence of metallo-beta-lactamase-producing CRKP, particularly strains harbouring dual carbapenemases. Timely recognition of high-risk patients, combined with the implementation of targeted infection control measures and the integration of novel therapeutic options, is crucial to optimize clinical management and reduce mortality associated with CRKP. Full article