Aniello Alfieri

Background/Objectives: Hydrogels are highly hydrated, biocompatible polymer networks increasingly investigated as drug-delivery systems (DDS) for analgesics. Their ability to modulate local release, prolong drug residence time, and reduce systemic toxicity positions them as promising platforms in perioperative, chronic, and localized pain settings. This scoping review aimed to systematically map clinical applications, efficacy, and safety of hydrogel-based DDS for analgesics, while also documenting non-DDS uses where the matrix itself contributes to pain modulation through physical mechanisms. Methods: Following PRISMA-ScR guidance, PubMed, Embase, and Cochrane databases were searched without publication date restrictions. Only peer-reviewed clinical studies were included; preclinical studies and non-journal literature were excluded. Screening and selection were performed in duplicate. Data extracted included drug class, hydrogel technology, clinical setting, outcomes, and safety. Protocol was registered with Open Science Framework. Results: A total of 26 clinical studies evaluating hydrogel formulations as DDS for analgesics were included. Most were randomized controlled trials, spanning 1996–2024. Local anesthetics were the most frequent drug class, followed by opioids, corticosteroids, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and neuromodulators. Application sites were predominantly topical/transdermal and perioperative/incisional. Across the DDS cohort, most of the studies reported improved analgesic outcomes, including reduced pain scores and lower rescue medication use; neutral or unclear results were rare. Safety reporting was limited, but tolerability was generally favorable. Additionally, 38 non-DDS studies demonstrated pain reduction through hydrogel-mediated cooling, lubrication, or barrier effects, particularly in burns, ocular surface disorders, and discogenic pain. Conclusions: Hydrogel-based DDS for analgesics show consistent clinical signals of benefit across diverse contexts, aligning with their mechanistic rationale. While current evidence supports their role as effective, well-tolerated platforms, translational gaps remain, particularly for hybrid nanotechnology systems and standardized safety reporting. Non-DDS applications confirm the intrinsic analgesic potential of hydrogel matrices, underscoring their relevance in multimodal pain management strategies.

Background/Objectives: Hydrogels are highly hydrated, biocompatible polymer networks increasingly investigated as drug-delivery systems (DDS) for analgesics. Their ability to modulate local release, prolong drug residence time, and reduce systemic toxicity positions them as promising platforms in perioperative, chronic, and localized pain settings. This scoping review aimed to systematically map clinical applications, efficacy, and safety of hydrogel-based DDS for analgesics, while also documenting non-DDS uses where the matrix itself contributes to pain modulation through physical mechanisms. Methods: Following PRISMA-ScR guidance, PubMed, Embase, and Cochrane databases were searched without publication date restrictions. Only peer-reviewed clinical studies were included; preclinical studies and non-journal literature were excluded. Screening and selection were performed in duplicate. Data extracted included drug class, hydrogel technology, clinical setting, outcomes, and safety. Results: A total of 26 clinical studies evaluating hydrogel formulations as DDS for analgesics were included. Most were randomized controlled trials (69%), spanning 1996–2024. Local anesthetics (46%) were the most frequent drug class, followed by opioids (19%), corticosteroids, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), and neuromodulators. Application sites were predominantly topical/transdermal and perioperative/incisional. Across the DDS cohort, 85% of studies reported improved analgesic outcomes, including reduced pain scores and lower rescue medication use; neutral or unclear results were rare. Safety reporting was limited but tolerability was generally favorable. Additionally, 38 non-DDS studies demonstrated pain reduction through hydrogel-mediated cooling, lubrication, or barrier effects, particularly in burns, ocular surface disorders, and discogenic pain. Conclusions: Hydrogel-based DDS for analgesics show consistent clinical signals of benefit across diverse contexts, aligning with their mechanistic rationale. While current evidence supports their role as effective, well-tolerated platforms, translational gaps remain, particularly for hybrid nanotechnology systems and standardized safety reporting. Non-DDS applications confirm the intrinsic analgesic potential of hydrogel matrices, underscoring their relevance in multimodal pain management strategies.

Cannabis sativa L. is a phytochemically rich plant with therapeutic potential across various clinical domains, including pain, inflammation, and neurological disorders. Among its constituents, terpenes are gaining recognition for their capacity to modulate the pathophysiological processes underlying chronic pain syndromes. Traditionally valued for their aromatic qualities, terpenes such as myrcene, β-caryophyllene (BCP), limonene, pinene, linalool, and humulene have demonstrated a broad spectrum of biological activities. Beyond their observable analgesic, anti-inflammatory, and anxiolytic outcomes, these compounds exert their actions through distinct molecular mechanisms. These include the activation of cannabinoid receptor type 2 (CB₂), the modulation of transient receptor potential (TRP) and adenosine receptors, and the inhibition of pro-inflammatory signalling pathways such as Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Cyclooxygenase-2 (COX-2). This narrative review synthesizes the current preclinical and emerging clinical data on terpene-mediated analgesia, highlighting both monoterpenes and sesquiterpenes, and discusses their potential for synergistic interaction with cannabinoids, the so-called entourage effect. Although preclinical findings are promising, clinical translation is limited by methodological variability, the lack of standardized formulations, and insufficient pharmacokinetic characterization. Further human studies are essential to clarify their therapeutic potential.

Cannabis sativa L. is a medicinally versatile plant rich in phytochemicals, among which terpenes are gaining recognition for their potential roles in modulating pain and inflammation. Traditionally appreciated for their aromatic characteristics, terpenes such as myrcene, β-caryophyllene (BCP), limonene, pinene, linalool and humulene have demonstrated diverse biological effects relevant to chronic pain syndromes. While the analgesic effects of cannabinoids like Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have been widely studied, growing evidence suggests that specific terpenes can exert antinociceptive, anti-inflammatory, and anxiolytic effects through distinct molecular mechanisms. These include activation of cannabinoid receptor 2 (CB₂) receptors, modulation of Transient receptor potential (TRP) and adenosine receptors, and inhibition of pro-inflammatory pathways such as Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and Cyclooxygenase-2 (COX-2). In addition, some terpenes influence glutamatergic, GABAergic, and opioid signalling, contributing to central and peripheral analgesia. This review synthesizes the current preclinical and emerging clinical data on terpene-mediated analgesia, highlighting both monoterpenes and sesquiterpenes, and discusses their potential for synergistic interaction with cannabinoids—the so-called entourage effect. Although preclinical findings are promising, clinical translation is limited by methodological variability, lack of standardized formulations, and insufficient pharmacokinetic characterization. Further human studies are essential to clarify their therapeutic potential.

Methicillin-resistant Staphylococcus aureus (MRSA) represents a major therapeutic challenge due to its multidrug-resistance and the associated clinical burden. Daptomycin (DAP), a cyclic lipopeptide antibiotic, has become a key agent for the treatment of severe MRSA infections owing to its rapid bactericidal activity and favourable safety profile. In this narrative review, we examine studies published between 2010 and April 2025. The data suggest that treatment with high-dose (8–10 mg kg⁻¹) DAP shortened the time to blood-culture sterilisation by a median of 2 days compared with standard-dose vancomycin without increasing toxicity when model-informed area-under-the-curve monitoring was employed. Particular attention is given to the synergistic effects of DAP combined with fosfomycin or β-lactams, especially ceftaroline and ceftobiprole, in overcoming persistent and refractory MRSA infections; this approach results in a reduction in microbiological failure relative to monotherapy. Resistance remains uncommon (mprF, liaFSR, and walK underscore the need for proactive genomic surveillance. Despite promising preclinical and clinical evidence supporting combination strategies, further randomized controlled trials are necessary to establish their definitive role in clinical practice, as are head-to-head cost-effectiveness evaluations. DAP remains a critical option in the evolving landscape of MRSA management, provided its use is integrated with precision dosing, resistance surveillance, and antimicrobial-stewardship frameworks.

Antimicrobial lock therapy (ALT) prevents microbial colonization in central vein catheters and treats existing catheter-related bloodstream infections (CRBSIs); the ALT assessment involves several key considerations. First, identifying which patients are suitable candidates is crucial. Additionally, understanding the clinical contexts in which is utilised provides insight into its applications. Examining when ALT has been employed and analyzing trends in its use over time can highlight its evolving role in patient care. Equally important is understanding how ALT is administered, including the specific agents used. Lastly, determining whether there is sufficient existing literature is essential to evaluate the feasibility of conducting future systematic reviews. This study is a scoping review adhered to the PRISMA-ScR guidelines and followed a five-stage methodological framework. Of the 1024 studies identified, 336 were included in the analysis. Findings highlight the widespread use of ethanol and taurolidine for CRBSIs prevention and the concurrent use of ALT with systemic antimicrobials to treat CRBSIs without catheter removal. ALT improves clinical outcomes, including post-infection survival and catheter retention. From our analysis, we have concluded that both an umbrella review of systematic reviews and a network meta-analysis comparing lock solutions can provide clearer guidance for clinical practice.

Antimicrobial lock therapy (ALT) prevents microbial colonisation in central vein catheters and treats existing catheter-related bloodstream infections (CRBSIs). Our objective was to assess the current scientific literature on the application of ALT and to address the following key questions: 1. Which patients are candidates for ALT? 2. In what clinical contexts is ALT employed? 3. When has ALT been used, and what are the trends in its application over time? 4. How is ALT administered, including specific agents such as antibiotics or ethanol? 5. Is there sufficient existing literature to support conducting a comprehensive systematic re-view on ALT? The scoping review followed a five-stage methodological framework, adhering to PRISMA-ScR guidelines. A total of 1024 studies were identified, with 336 ultimately included in the final analysis. The findings showed that ALT involves the use of ethanol and taurolidine for preventing CLAB-SIs, while ALT is used alongside systemic antimicrobial treatment for CRBSIs when catheter re-moval is not feasible. In conclusion, ALT demonstrates its potential to improve clinical outcomes, including better post-infection survival rates and prolonged catheter retention. Further systematic reviews are needed to strengthen these findings and provide clearer guidance for clinical practice.

Alcohol withdrawal syndrome (AWS) is defined as the cessation or reduction in heavy and prolonged alcohol use within several hours to a few days of cessation. The recommended first-line therapy for AWS ranging from mild to severe or complicated remains benzodiazepines; in cases where benzodiazepines are not adequate in controlling persistent autonomic hyperactivity or anxiety, dexmedetomidine could be utilized. The possible advantage of dexmedetomidine compared to benzodiazepines is that it does not cause respiratory depression, thus reducing the risk of intubation and hospitalization in the ICUs, with the potential reduction in healthcare costs. The purpose of this systematic review and meta-analysis (PROSPERO CRD42018084370) is to evaluate the effectiveness and safety of dexmedetomidine as adjunctive therapy to the standard of care for the treatment of AWS. We retrieved literature from PubMed, EMBASE, and CENTRAL until 10 January 2024. Eligible studies were both randomized trials and nonrandomised studies with a control group, published in the English language and peer-reviewed journals. The primary outcome was tracheal intubation; secondary outcomes were (i) bradycardia and (ii) hypotension. A total of 3585 papers were retrieved: 2635 from EMBASE, 930 from Medline, and 20 from CENTRAL. After eliminating duplicates, 2960 papers were screened by title and abstract; 75 out of the 2960 papers were read in full text. The qualitative synthesis included nine of all manuscripts read in full text. The quantitative synthesis included eight studies for the primary outcome (tracheal intubation), seven for the secondary outcome bradycardia, and six for the secondary outcome hypotension. The meta-analysis showed that Dexmedetomidine, as adjunctive therapy, is not more effective than standard therapy in reducing the risk of tracheal intubation in AWS [RR: 0.57, 95% CI: 0.25–1.3, p = 0.15]. It also appears to be less safe than sedative therapy as it significantly increases the risk of bradycardia [RR: 2.68, 95% CI: 1.79–4.16, p = 0.0016]. Hypotension was not significantly different in patients who received dexmedetomidine [RR: 1.5, 95% CI: 0.69–3.49, p = 0.21].

Abdominal surgical site infections (SSIs) are infections that occur after abdominal surgery. They can be superficial, involving the skin tissue only, or more profound, involving deeper skin tissues including organs and implanted materials. Currently, SSIs are large global health problem with an incidence that varies significantly depending on the United Nations’ Human Development Index. The purpose of this review is to provide a practical update on the latest available literature on SSIs, focusing on causative pathogens and treatment with an overview of the ongoing studies of new therapeutic strategies.

For thousands of years, medicinal cannabis has been used for pain treatment, but its use for pain management is still controversial. Meta-analysis of the literature has shown contrasting results on the addition of cannabinoids to opioids compared with placebo/other active agents to reduce pain. Clinical studies are mainly focused on medicinal cannabis use in chronic pain management, for which the analgesic effect has been proven in many studies. This review focuses on the potential use of medical cannabis for acute pain management in preclinical studies, studies on healthy subjects and the few pioneering studies in the clinical setting.