Search Results (4,049)

Background/Objectives: Biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) have expanded treatment options for inflammatory rheumatic diseases, highlighting the need for continuous pharmacovigilance. This study evaluated changes in prescribing patterns and safety profiles of b/tsDMARDs between 2018–2019 and 2023–2024 in routine clinical practice. Methods: A retrospective observational study was conducted in patients with rheumatoid arthritis (AR), psoriatic arthritis (PsA), ankylosing spondylitis (AS), or juvenile idiopathic arthritis (JIA) treated at a rheumatology outpatient clinic in Southern Italy. Demographic and clinical characteristics, prescribed therapies, treatment switches/swaps, therapeutic failures, and adverse events (AEs) were collected through a structured pharmacovigilance program. Prescribing trends between the two study periods were compared using chi-square analysis. Results: A total of 342 patients were included (202 in 2018–2019 and 140 in 2023–2024). Prescribing patterns changed significantly over time (χ² = 83.24, p < 0.0001), with increased use of newer therapeutic classes and biosimilars, while tumor necrosis factor (TNF) inhibitors remained the most frequently prescribed drugs. The proportion of biologic-naïve patients increased from 52.0% to 66.4%, whereas AEs decreased from 31.7% to 15.0%, with no serious adverse events (SAEs) reported. Conclusions: Prescribing strategies for inflammatory rheumatic diseases evolved substantially between 2018 and 2024, reflecting the availability of new therapeutic options and a more personalized treatment approach. b/tsDMARDs showed a favorable real-world safety profile, supporting the importance of ongoing pharmacovigilance. Full article

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) remain the cornerstone of pharmacological treatment for osteoarthritis (OA) and are recommended by international guidelines for the management of symptomatic pain. Despite their well-established efficacy, substantial interindividual variability exists in treatment response, with some patients experiencing meaningful pain relief while others derive little clinical benefit despite appropriate drug selection and dosing. This variability reflects, at least in part, the biological heterogeneity of OA pain. Objective: To review the mechanisms underlying variability in NSAID responsiveness in OA and to propose a practical framework for personalized NSAID prescribing based on pain phenotype, individual safety profile, and treatment timing. Methods: A narrative review of the contemporary scientific literature was conducted using major biomedical databases to summarize the current evidence on phenotype-guided NSAID therapy in OA. Particular attention was given to the emerging concepts of nociceptive, nociplastic, and neuropathic-like pain phenotypes and their implications for personalized anti-inflammatory therapy. Results: Current evidence indicates that OA pain is a heterogeneous and dynamic condition in which inflammatory nociceptive, nociplastic, and neuropathic-like mechanisms coexist to varying degrees. NSAIDs primarily target inflammatory nociceptive pain by inhibiting cyclooxygenase (COX)-mediated prostaglandin synthesis and reducing peripheral sensitization. Consequently, patients with predominantly inflammatory nociceptive pain are the most likely to benefit from NSAID therapy, whereas those with predominant nociplastic or neuropathic-like pain mechanisms may require alternative or multimodal treatment strategies. Beyond pain phenotype, optimal NSAID selection should integrate cardiovascular, gastrointestinal, and renal risk assessment, recognizing the important pharmacological and safety differences among individual agents. Treatment timing is also clinically relevant, as anti-inflammatory therapy appears most effective when initiated during periods of active inflammatory nociceptive pain. Based on the available evidence, we propose a conceptual clinical decision framework integrating patient selection, NSAID choice, and treatment timing. Conclusions: Personalized NSAID prescribing should move beyond a diagnosis-based approach toward a mechanism-based strategy that integrates pain phenotyping, individualized safety assessment, and appropriate treatment timing. The proposed framework is built upon three complementary principles, identifying the right patient, selecting the right treatment, and initiating therapy at the right time. It provides a practical foundation for implementing precision medicine in the pharmacological management of OA. Full article

The temporomandibular joint (TMJ) is a highly specialized synovial joint responsible for essential functions such as mastication, speech, and swallowing. Owing to its unique anatomical organization, complex biomechanics, and heterogeneous tissue composition, regeneration of the TMJ remains one of the greatest challenges in craniofacial reconstructive surgery. Conventional treatment modalities, including autologous grafts, alloplastic prostheses, and total joint replacement, are associated with several limitations, including donor-site morbidity, prosthetic wear, limited biological integration, and the inability to restore native tissue architecture. Three-dimensional (3D) bioprinting has emerged as a promising regenerative strategy capable of fabricating patient-specific living constructs that closely mimic the structural and functional characteristics of the native joint. This review summarizes recent advances in TMJ bioprinting, with particular emphasis on the regeneration of the mandibular condylar fibrocartilage, subchondral bone, articular disc, and integrated osteochondral constructs. The literature search covered publications from January 2010 through March 2026, and it was conducted using major scientific databases, including PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Current progress in cellular sources, including mesenchymal stem cells and induced pluripotent stem cells, biomaterials and bioinks, growth factor delivery, and multimaterial bioprinting technologies is discussed. Particular attention is given to the challenges associated with reproducing the complex osteochondral interface, achieving adequate vascularization, ensuring long-term mechanical stability, and directing tissue-specific cell differentiation. Emerging technologies, including four-dimensional (4D) bioprinting, decellularized extracellular matrix-based bioinks, artificial intelligence-assisted design, patient-specific computational modeling, and bioreactor-mediated tissue maturation, are highlighted as promising approaches to improve construct functionality and clinical translation. Although the clinical application of TMJ bioprinting remains in its early stages, rapid advances in regenerative medicine and biofabrication technologies indicate that personalized bioengineered joint reconstruction may become a viable therapeutic option for the treatment of severe temporomandibular joint disorders in the future. Full article

Antiretroviral therapy (ART) is essential for preventing HIV transmission and improving the health outcomes of people living with HIV (PLHIV). However, many barriers limit PLHIV from starting and adhering to ART, which explains why HIV responses in many settings, including Indonesia, have produced limited gains. This qualitative phenomenological study explored multilevel barriers to ART adherence in urban Yogyakarta (locally known as Jogja) and rural Belu, Indonesia, from the perspectives of PLHIV and healthcare professionals (HCPs). Data were collected through one-on-one in-depth interviews with 92 PLHIV and 20 HCPs. Participants were recruited using the snowball sampling technique. Data were analysed using framework analysis informed by the Access to Healthcare Framework. The findings showed that PLHIV in Belu and Jogja had different experiences in terms of the provision of and ability to access and adhere to ART or HIV treatment. In rural Belu, ART was less available and visible, harder to approach, often unaffordable, less aligned with patients’ needs, and strongly influenced by the widespread use of traditional medicine. PLHIV in Belu also reported a more limited ability to perceive the need for ART, reach services, pay costs, engage in care, and seek ART than those in urban Jogja. Personal, psychological, and social barriers were also reported to hinder PLHIV’s ART adherence in both settings. These findings highlight the need for HIV policies that promote the equitable distribution of ART services and targeted interventions to improve understanding and acceptance of HIV care among PLHIV and the wider community. Full article

Background: Hypertrophic scarring remains a common and clinically challenging consequence of burn injury. Although compression therapy is widely used, its effectiveness is limited by variability in pressure delivery, lack of personalization and inconsistent treatment protocols. Methods: This prospective single-centre feasibility study included adult patients with post-burn scars following deep partial-thickness or full-thickness injuries. The study was designed as a two-phase workflow. In Phase I, scars were documented using standardized photography and 3D surface scanning and were evaluated using the Vancouver Scar Scale (VSS). Scars were stratified based on a predefined threshold (VSS >6) for progression to intervention. In Phase II, patient-specific compression matrices will be designed from 3D surface data and fabricated using biocompatible material. Computational modeling using finite element analysis (FEA) will be applied to simulate pressure distribution. Follow-up is planned at 1, 3, and 6 months, with the VSS as the primary outcome measure. Results: A total of 27 scars were included. The median VSS score was 7 (IQR 5–8). Based on stratification, 14 scars (51.9%) were eligible for personalized compression therapy. Three-dimensional imaging was feasible in all cases and allowed for improved qualitative visualization of scar morphology compared to standard photography. Preliminary findings support the applicability of the proposed workflow, while longitudinal outcome analysis is ongoing. Conclusions: This feasibility study presents and evaluates a clinical workflow combining 3D imaging, objective scar stratification, and personalized compression therapy. This approach provides a structured framework for personalized compression therapy, while its clinical effectiveness remains to be established. Further studies are required to evaluate long-term outcomes. Full article

Background/Objectives: Male chronic pelvic pain syndrome (CPPS) is a heterogeneous condition involving overlapping urinary, psychosocial, organ-specific, infectious, neurological, myofascial, and sexual phenotypes. This complexity limits the effectiveness of routine symptom assessment and empirical treatment strategies. Artificial intelligence (AI) may support more reproducible interpretation, differential diagnosis, phenotyping, and personalized management. This up-to-date narrative mapping review aimed to identify AI-assisted approaches that are directly or indirectly relevant to the assessment of males with CPPS, classify them according to UPOINTS phenotypic domains and clinical functions, and critically discuss the extent to which current evidence is disease-specific or extrapolated from related conditions. Methods: A literature search was performed in PubMed/MEDLINE, the Cochrane Library, and Google Scholar from database inception to May 2026 using terms related to male CPPS, UPOINTS domains, diagnosis, treatment, prognosis, digital solutions, artificial intelligence, machine learning, deep learning, natural language processing, computer vision, and decision support. Studies were included if they described AI-based or AI-adjacent computational approaches relevant to male CPPS or to related conditions important for UPOINTS-based phenotyping, differential diagnosis, or phenotype-specific assessment. Results: Available evidence remains fragmented and is largely extrapolated from related urological, chronic pain, pelvic floor, infectious, neurological, and sexual medicine conditions. AI applications were most developed in urinary and organ-specific domains, including uroflowmetry analysis, bladder volume assessment, cystoscopy, prostate imaging, urinary biomarkers, and differential diagnosis of lower urinary tract disorders. AI tools also showed potential for infection detection, psychosocial screening, chronic pain monitoring, neuroimaging-based phenotyping, pelvic floor dysfunction assessment, and evaluation of sexual dysfunction. However, male-CPPS-specific validation remains limited. Conclusions: AI has promising potential to improve differential diagnosis, multidomain phenotyping, and individualized management in males with CPPS. Current evidence is mainly translational and hypothesis-generating. Future studies should focus on prospective male-CPPS-specific cohorts, external validation, explainable multimodal models, and integration of AI tools into clinically meaningful, patient-centered workflows. Full article

Background: Carotid free-floating thrombus (CFFT) is an uncommon but clinically significant cause of transient ischemic attack and ischemic stroke, carrying a substantial risk of recurrent cerebral embolization. Despite advances in vascular imaging, the optimal management of CFFT remains controversial because available recommendations are largely based on retrospective studies, case series, and expert opinion. The present study reports a single-center experience with CFFT and provides an updated narrative review of current diagnostic and therapeutic strategies, with particular attention to the timing of intervention. Methods: A retrospective review of patients diagnosed with CFFT and managed at our institution over a 20-year period was performed. Clinical presentation, imaging findings, treatment strategy, and outcomes were analyzed. In parallel, a narrative review of the contemporary literature was conducted to summarize current evidence regarding medical management, carotid endarterectomy, endovascular techniques, hybrid approaches, and emerging concepts related to thrombus composition and maturation. Results: Five patients with symptomatic CFFT were identified. Four patients underwent carotid thromboendarterectomy, whereas one patient was managed medically with anticoagulation and antiplatelet therapy, resulting in complete thrombus resolution. Two patients experienced neurological deterioration while receiving initial anticoagulation and subsequently required urgent surgical intervention. No postoperative strokes occurred after carotid endarterectomy. Review of the literature confirmed that anticoagulation remains the cornerstone of initial therapy and achieves thrombus resolution in a substantial proportion of patients. However, recurrent neurological events continue to occur under medical treatment, while the indications and timing of invasive intervention remain poorly defined. Recent advances in high-resolution magnetic resonance imaging and optical coherence tomography suggest that thrombus age and composition may become important determinants of future treatment selection. Conclusions: CFFT represents a rare but potentially unstable vascular condition for which high-quality evidence is still lacking. Initial anticoagulation remains the most widely accepted treatment strategy, while carotid endarterectomy, endovascular thrombectomy, carotid artery stenting, and hybrid procedures may be appropriate in selected patients. Future management algorithms may ultimately move beyond a one-size-fits-all approach by incorporating thrombus biology, imaging characteristics, and individual patient risk profiles. Although this concept remains preliminary, advances in thrombus characterization may provide the foundation for more personalized treatment strategies as further clinical evidence becomes available. Full article

Background/Objectives: Achieving guideline-recommended low-density lipoprotein cholesterol (LDL-C) targets in patients with chronic coronary syndrome (CCS) remains challenging despite intensive lipid-lowering therapy. Bempedoic acid (BA) offers an oral therapeutic option, although data on its clinical performance and patient-level determinants of response in real-world Spanish settings are limited. Methods: We conducted a prospective multicentre study across the four healthcare areas of Cáceres province, Spain, including consecutive CCS patients with LDL-C ≥ 55 mg/dL despite stable intensive lipid-lowering therapy. BA 180 mg/day was added to background treatment. Lipid parameters, metabolic profile, and safety outcomes were assessed after a median follow-up of 28 weeks (IQR 23–47). Multivariable analyses were performed to identify factors associated with of LDL-C reduction and target attainment. A total of 118 patients were analyzed for outcomes. Results: A total of 118 patients (mean age 62.4 ± 10.0 years; 79.2% male) were included. BA reduced LDL-C by 22.8% (−16.36 mg/dL; p < 0.001), enabling 48.3% of patients to achieve LDL-C < 55 mg/dL. Higher baseline LDL-C (β = −0.515; p = 0.001) and the presence of diabetes mellitus (B = 13.8 mg/dL; p = 0.024) were independently associated with greater LDL-C reduction. Notably, 56.3% of patients presented with elevated baseline lipoprotein(a) levels (>50 mg/dL), describing a high underlying burden of residual risk. BA was well tolerated, with a modest increase in uric acid levels but no gout events and a high treatment persistence rate (94.4%). Conclusions: In a real-world CCS population receiving intensive lipid-lowering therapy, BA provides clinically meaningful LDL-C reduction with a favorable safety profile in this multicentre cohort from Cáceres province. Patients with higher baseline LDL-C and diabetes derive greater benefit, supporting a more personalized approach to therapy. These findings reinforce the role of BA in Spanish patients as an intermediate step in lipid-lowering strategies before escalation to more costly therapies, addressing the scarcity of local real-world data. Full article

Background: Although the diagnostic and treatment pathway for Obstructive Sleep Apnea (OSA) is well established, long-term management is still not standardized. Methods: We conducted a narrative review of studies published between 2000 and 2026 in PubMed/MEDLINE. Results: Continuous Positive Airway Pressure (CPAP) adherence and healthcare resource allocation remain the real critical issue of long-term management for OSA patients. Early proactive interventions like phone calls and early medical visits may be particularly valuable for improving CPAP nightly usage. Telemedicine, educated and trained home-care providers or primary care can lead to improved adherence, long-term monitoring and earlier identification of treatment-related issues. Patient-reported outcomes, comorbidities, endotypes, and phenotypic stratification should be integrated into follow-up management. Conclusions: OSA long-term care should shift from a device-centered approach toward a personalized, patient-centered model with the integration of multidimensional risk stratification, multidisciplinary care, telemedicine and primary care support. Full article

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide despite substantial advances in surgery, chemotherapy, targeted therapies, and immunotherapy. The limited efficacy of current treatment strategies in advanced disease and the emergence of therapeutic resistance highlight the urgent need for novel adjunctive therapeutic approaches. Increasing evidence indicates that chronic stress and sustained activation of β-adrenergic signaling promote colorectal tumor initiation, progression, angiogenesis, metastatic dissemination, and immune evasion, thereby identifying this pathway as a potential therapeutic target. Drug repurposing has emerged as an attractive strategy for accelerating the development of new anticancer therapies by identifying novel applications for clinically approved drugs with well-established safety profiles. Among these, β-blockers have gained considerable attention because of their ability to inhibit β-adrenergic signaling and modulate multiple oncogenic pathways implicated in CRC progression. Although accumulating preclinical and observational clinical evidence suggests that β-blockers may possess anticancer potential, the underlying molecular mechanisms and their translational relevance have not yet been comprehensively integrated. This review provides a critical overview of the current evidence regarding the therapeutic potential of β-blockers in CRC by integrating findings from preclinical and clinical studies. Particular emphasis is placed on the regulation of key signaling pathways, including cAMP/PKA/CREB, PI3K/AKT/mTOR, and RAS/RAF/MEK/ERK, as well as on the effects of β-blockers on tumor cell proliferation, apoptosis, angiogenesis, epithelial–mesenchymal transition, metastasis, and modulation of the tumor microenvironment and antitumor immune responses. However, significant barriers limit the translation of these findings into routine clinical practice, including the limited representativeness of preclinical models, potential hemodynamic adverse effects, and the inherent limitations of observational studies. Importantly, owing to the lack of prospective randomized clinical trials, the current evidence remains insufficient to establish the clinical efficacy of β-blockers in CRC. Although β-blockers possess several characteristics that make them attractive candidates for drug repurposing, including a well-established safety profile, widespread availability, and low cost, further mechanistic studies, prospective randomized clinical trials, and biomarker-based patient stratification are essential to determine their clinical efficacy and define their role in personalized CRC therapy. Full article

The integration of precision nutrition with pharmacological therapies has been proposed as a strategy to optimize therapeutic efficacy, tolerability, and patient-centered outcomes in chronic metabolic diseases. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have substantially advanced the treatment of obesity and type 2 diabetes mellitus by promoting substantial weight loss and improving glycemic control and cardiometabolic risk profiles. However, significant interindividual variability in therapeutic response, frequent gastrointestinal adverse events leading to treatment discontinuation, and the potential loss of lean body mass remain major clinical challenges that limit real-world therapeutic efficiency. Emerging evidence suggests that nutritional status, dietary patterns, body composition, inflammatory burden, and gut microbiota composition may influence both the efficacy and tolerability of GLP-1-based therapies. This review explores the role of precision nutrition as an adjunctive strategy to support GLP-1 RA treatment outcomes through personalized dietary interventions and targeted nutritional support. Particular attention is given to protein intake optimization for lean mass preservation, micronutrient adequacy, microbiota modulation, anti-inflammatory dietary approaches, and the management of gastrointestinal symptoms. Furthermore, the review explores the emerging contribution of nutrigenomics, metabolomics, microbiome-based stratification, digital health technologies, and artificial intelligence in advancing pharmacometabolic personalization. The potential pharmacoeconomic implications of integrated nutritional–pharmacological strategies are discussed, including the potential for improved adherence to reduce treatment-related costs, prevent complications, and enhance long-term metabolic sustainability. While current evidence supports the mechanistic rationale for combining precision nutrition with GLP-1 receptor agonist therapy, it must be emphasized that direct evidence from prospective clinical trials evaluating such integrated strategies is limited. Most recommendations are based on indirect evidence from general weight-loss or metabolic disease populations, and their efficacy, specifically in GLP-1 RA-treated patients, remains to be demonstrated. Full article

The widespread adoption of in vitro fertilization (IVF) has profoundly transformed the management of infertility and established IVF as the most effective assisted reproductive technology for many clinical indications. Nevertheless, intrauterine insemination (IUI) remains widely used because of its lower invasiveness, reduced treatment burden, lower costs, and broader accessibility. The contemporary role of IUI in an IVF-dominated era remains a subject of ongoing debate. This narrative review aims to critically evaluate the current role of IUI in modern reproductive medicine by examining its clinical indications, effectiveness, limitations, cost-effectiveness, and patient-centered implications in comparison with IVF. A narrative review of the literature was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar. Relevant studies, systematic reviews, meta-analyses, randomized controlled trials, and international guidelines published primarily between 2010 and 2025 were identified and synthesized. Particular attention was given to recommendations from the European Society of Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM). Current evidence supports the use of IUI, particularly when combined with ovarian stimulation, as an appropriate first-line treatment in selected couples with unexplained infertility, mild male-factor infertility, and minimal-to-mild endometriosis. Although IVF generally provides higher live birth rates per treatment cycle and remains the preferred option for several infertility diagnoses, IUI continues to offer meaningful clinical benefits in appropriately selected patients. Beyond effectiveness, treatment decisions should also consider cost-effectiveness, accessibility, treatment burden, safety, and patient preferences. Recent evidence increasingly supports individualized and prognosis-based approaches to fertility treatment selection. Evidence also highlights the importance of female age, infertility duration, and ovarian reserve in determining the relative benefit of IUI versus IVF. Despite the clinical dominance of IVF, IUI remains an evidence-based and clinically relevant component of contemporary fertility care. Rather than being viewed as competing interventions, IUI and IVF should be considered complementary treatment options within a personalized infertility management strategy. Appropriate patient selection, particularly considering female reproductive prognosis, remains essential to maximize reproductive outcomes while minimizing treatment burden and healthcare costs. Full article

Glomerulosclerosis is not an independent disease entity but rather a common histopathological endpoint shared by diverse glomerular diseases and chronic kidney disorders. It represents the final common pathway of progressive glomerular injury and is a major determinant of chronic kidney disease (CKD) progression. Accordingly, this review focuses on the shared cellular and molecular mechanisms that drive glomerulosclerosis, together with current diagnostic strategies, mechanism-based therapeutic approaches, and future directions toward precision nephrology. We begin by summarizing the structural and functional features of the glomerulus and outlining the key molecular mechanisms that drive sclerosis, including podocyte loss, mesangial matrix expansion, endothelial dysfunction, inflammation, and fibrosis-related signaling pathways. The clinical and pathological classifications of glomerular diseases associated with glomerulosclerosis—ranging from primary and secondary focal segmental glomerulosclerosis (FSGS) to diabetic, hypertensive, and immune-mediated forms—are discussed in detail. We further review current diagnostic approaches, including renal biopsy patterns, emerging biomarkers, and novel imaging and digital pathology tools that enable earlier and more precise assessment of disease severity. Recent advances in treatment are summarized across conservative, immunologic, and targeted therapeutic categories, with emphasis on SGLT2 inhibitors, endothelin receptor antagonists, immunomodulatory agents, and antifibrotic compounds. Finally, we highlight rapidly evolving therapeutic and technological advances, including podocyte-directed interventions, APOL1-targeted therapies, RNA- and gene-based therapeutics, and artificial intelligence-driven precision nephrology. These emerging approaches are reshaping the management paradigm of glomerular diseases by enabling molecular disease stratification and personalized treatment strategies. Despite substantial progress, significant unmet needs remain, particularly concerning early detection, individualized treatment selection, and the marked heterogeneity of disease mechanisms across patient populations. Overall, this review provides an integrated framework for understanding glomerulosclerosis as a shared pathological endpoint of diverse glomerular diseases and highlights emerging mechanism-based therapeutic strategies that support the transition toward precision nephrology. Full article

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that arises from a complex interplay of genetic susceptibility, immune dysregulation, environmental exposures, and altered host–microbiome interactions. Increasing evidence identifies the gut microbiota as a central component of IBD pathogenesis. In healthy individuals, the intestinal microbiota supports epithelial integrity, metabolic homeostasis, immune education, colonization resistance, and bidirectional gut–brain communication. In IBD, this ecosystem is disrupted by reduced microbial diversity, expansion of pathobionts, and broader functional alterations affecting community stability and metabolic output. Importantly, these changes are increasingly viewed not merely as consequences of inflammation, but as active contributors to disease development and persistence. Dysbiosis may also influence neuroimmune signaling through the gut–brain axis, linking microbial metabolites, intestinal barrier dysfunction, enteric nervous system activity, and psychological comorbidities frequently observed in patients with IBD. This review provides a comprehensive overview of the role of the gut microbiota in IBD, beginning with its physiological functions in intestinal homeostasis and the evidence linking dysbiosis to disease pathogenesis, followed by a critical evaluation of current microbiome-based therapeutic strategies, their translational challenges, and prospects for personalized microbiota-directed interventions. Approaches such as fecal microbiota transplantation (FMT), probiotics, live biotherapeutic products, and genetically engineered bacteria aim to restore microbial balance and modulate intestinal inflammation. Among these, FMT has provided the strongest proof-of-concept for microbiome restoration, whereas probiotic efficacy remains variable and strain-dependent. Emerging defined microbial consortia and engineered bacterial platforms offer improved standardization and mechanistic precision, but their clinical application remains limited by challenges related to engraftment, durability of response, safety, and treatment optimization. Collectively, current evidence supports gut microbiota as both a key determinant of IBD pathogenesis and a promising therapeutic target, underscoring the need for more precise and personalized microbiota-directed approaches in IBD management. Full article

Sepsis and septic shock remain leading causes of disability, mortality and healthcare utilization worldwide. Increasing evidence has established sepsis as a time-dependent emergency in which delays in diagnosis and treatment are associated with worsening organ dysfunction and increased mortality. To standardize early management, the Surviving Sepsis Campaign (SSC) developed evidence-based care bundles, culminating in the current Hour-1 Bundle, which emphasizes rapid implementation of key diagnostic and therapeutic interventions. This narrative review critically examines the scientific rationale, clinical evidence, implementation challenges, and future perspectives surrounding the SSC Hour-1 Bundle. Lactate remains a valuable marker of illness severity and treatment response, although its interpretation requires consideration of multiple non-hypoperfusion-related mechanisms. Blood cultures represent the microbiological gold standard, while emerging rapid diagnostic technologies are transforming pathogen identification and antimicrobial stewardship. Early effective antimicrobial therapy remains strongly associated with improved outcomes, although balancing prompt treatment with antimicrobial stewardship remains challenging. Fluid resuscitation strategies have evolved from fixed-volume approaches toward individualized assessment of fluid responsiveness and tolerance, whereas early vasopressor initiation is increasingly recognized as complementary to fluid administration. Although observational studies frequently associate bundle adherence with improved outcomes, real-world compliance remains variable and evidence supporting strict one-hour completion targets remains heterogeneous. Future developments are expected to move beyond standardized protocols toward personalized sepsis management integrating rapid diagnostics, immune phenotyping, advanced haemodynamic monitoring, and artificial intelligence-driven clinical decision support. These innovations may enable more precise therapeutic strategies while preserving the fundamental principles of sepsis management, that remain the cornerstone of contemporary sepsis care. Full article