Introduction: Bisphosphonates (BPs) are commonly used to treat osteoporosis as well as Bone Marrow Edema (BME). Potential adverse effects include hypocalcemia, flu-like symptoms, musculoskeletal pain, gastrointestinal issues, and, rarely, osteonecrosis of the jaw. This study evaluated the safety of intramuscular formulations of neridronate, clodronate, and their sequential combination in patients with BME. Methods: A retrospective observational study was performed on 128 outpatients referred for BME between May 2020 and June 2025. Primary outcome was reduction in clinical symptoms; secondary outcomes included Adverse Drug Reactions (ADRs) and Drug–Drug Interactions (DDIs). results: In this study we enrolled 128 patients (69 females and 59 males) with a median age of 66 years (IQR: 54.5-75). The median number of sessions needed for recovery differed depending on the drug group: Neridronate took 4 sessions (IQR: 3–4), Clodronate took 12 sessions (IQR: 5–23), and the combination of Clodronate and Neridronate took 14 sessions (IQR: 9–23). No significant interactions were observed between drug type and sex, age, or the presence of other diseases. Results: Median age was 66 years (IQR: 54.5–75), with 69 females and 59 males. Median sessions to recovery were 4 (neridronate), 12 (clodronate), and 14 (combination). Negative binomial regression showed that significantly more sessions were required for clodronate and combination therapy compared with neridronate. No severe ADRs occurred, despite polytherapy and potential DDIs. Male patients showed a non-statistically significant trend to a lower number of sessions and potentially inappropriate prescription. The number of medications was the only factor directly related to DDIs (p < 0.05). Discussion: The lower number of median sessions for clodronate was likely due to a small sample size. The low number of side effects is probably related to intramuscular administration. Factors like age and sex can be relevant in the onset of DDIs in other clinical contexts, but our population displayed a relatively low median age. Conclusion: Bisphosphonates were safe and effective for BME in our cohort, with a low risk of clinically relevant DDIs. However, larger studies are needed to confirm these results.

Direct oral anticoagulants (DOACs) are widely prescribed in patients at risk of thromboembolism. Although they are generally safer than warfarin, DOACs still carry a risk of bleeding and drug-drug interactions (DDIs). Nociceptive pain is common and may frequently occur in patients receiving DOAC therapy. In these cases, the European Society of Cardiology recommends avoiding non-steroidal anti-inflammatory drugs (NSAIDs) and preferring acetaminophen. However, acetaminophen is not effective when an inflammatory component is present. Consequently, non-pharmacological approaches or topical NSAIDs are suggested, while, in selected cases, lower-risk NSAIDs such as ibuprofen may be considered. Available evidence clearly indicates that concomitant treatment with NSAIDs and DOACs is associated with an increased risk of bleeding, although the magnitude of risk appears to differ across compounds. In this narrative review, we summarize the current evidence on bleeding risk associated with NSAID-DOAC coadministration, discuss potential DDIs from a pharmacokinetic perspective, and outline directions for future research.

Background/Objectives: Interest in the use of nutraceuticals and phytotherapy for the management of andrological diseases has increased markedly in recent years. In particular, growing attention has been directed toward the treatment of patients affected by erectile dysfunction (ED), male infertility, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and induratio penis plastica (IPP). However, several areas of uncertainty remain. This narrative review aims to examine the role of nutraceuticals and phytotherapeutic agents in the management of andrological disorders. Methods: A narrative review was conducted using PubMed, Scopus, Cochrane CENTRAL, and EMBASE to identify relevant studies published over the past 25 years. Only articles published in English and involving adult populations were included in the analysis. Results: Nutraceuticals and phytotherapeutic compounds have been extensively investigated in the current literature, and certain formulations—particularly specific combinations—have been evaluated in high-quality studies. Conversely, other compounds lack sufficient scientific evidence and therefore should not be recommended in routine clinical practice. In the management of ED, the following compounds, administered either alone or in combination, have demonstrated clinically significant effects: Panax ginseng, Tribulus terrestris, L-arginine, and Withania somnifera. L-carnitine, combined with micronutrients, antioxidants, and various traditional herbal supplements, appears to be an effective therapeutic option for male infertility and subfertility. Pollen extracts play an important role in the management of CP/CPPS, while carnitine, coenzyme Q10, silymarin, bromelain, and curcumin show promising potential in the treatment of IPP. Conclusions: Nutraceuticals and phytotherapeutic agents may provide favorable outcomes in the management of andrological diseases. Although current evidence is encouraging, larger prospective studies employing standardized protocols and treatment schedules are required to confirm long-term efficacy and to optimize therapeutic strategies.

Background: Nutraceuticals are increasingly used in clinical practice for their anti-inflammatory, antiproliferative, and antioxidant properties. This study aimed to evaluate the safety and efficacy of a fixed nutraceutical combination containing chondroitin sulfate, α-lipoic acid, astaxanthin, lycopene, escin, and omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) in improving pain and quality of life in patients with chronic knee osteoarthritis (OA). Methods: This observational study included patients with chronic knee OA who were referred to the ambulatory pain clinic at Dulbecco University Hospital, Catanzaro, Italy. Participants received one tablet daily for three months. Quality of life was assessed using the 36-Item Short Form Health Survey (SF-36), and adverse drug reactions (ADRs) were evaluated using the Naranjo scale. Results: Fifty patients (20 men and 30 women; mean age, 63.6 ± 11.4 years; range, 26–88 years; mean body mass index, 26.9 ± 3.7 kg/m2) were enrolled. Pain symptoms demonstrated a statistically significant improvement over time (p < 0.01). No ADRs were reported during the study period. Conclusions: The fixed nutraceutical combination improved pain and quality of life in patients with chronic knee OA and demonstrated an excellent safety profile.

Tenecteplase, a genetically modified recombinant tissue plasminogen activator with a long half-life, has recently been proposed as a valid alternative to alteplase for thrombolysis in patients with acute ischemic stroke. According to clinical studies and trials, tenecteplase has several practical advantages over alteplase, including administration by single bolus rather than continuous infusion, shorter treatment duration, and possibly associated with fewer complications. Not only do these features increase the efficiency of emergency department workflow, but they also enable faster reperfusion and more rapid transfer to thrombectomy-capable centers. Although clinical evidence strongly suggests that tenecteplase has greater efficacy and safety, its use may lead to implemented "bridging therapy" in terms of rapid administration of a full dose of intravenous fibrinolytics before endovascular thrombectomy, enhanced recanalization rates, and improved efficacy of thrombolytic treatment in ischemic stroke patients.

Background and objectives: Fibromyalgia (FM) is diagnosed using symptom-based criteria, and clinician-assigned labels frequently diverge from them. FM also coexists with pain-generating musculoskeletal disorders. We determined how many patients referred or labeled as having FM fulfilled the 2019 ACTTION-American Pain Society Pain Taxonomy (AAPT) criteria after specialist assessment and compared concomitant pain-related diagnoses and symptom severity by AAPT status. Methods: Single-center cross-sectional pilot study of consecutive adult outpatients attending a pain unit for suspected or previously diagnosed FM. Clinical records were reviewed to determine fulfilment of the AAPT 2019 criteria, identify documented concomitant pain-related diagnoses, and assess symptom severity (FIQR, Zung SAS/SDS, DN4, NRS). Results: Among 76 patients (96.1% female), 28 fulfilled the AAPT criteria (36.8%; 95% CI, 26.9–48.1%). Of these, 25 (89.3%; 95% CI, 72.8–96.3%) had at least one documented concomitant pain-related diagnosis, versus 54.2% of those not fulfilling the criteria (OR, 7.05; 95% CI, 1.87–26.54; p = 0.002). AAPT MET patients had higher FIQR, SAS, SDS and DN4 scores, whereas NRS did not differ significantly. Conclusion: Approximately one-third of patients with an FM label fulfilled the AAPT criteria, and most of those who did also had a concomitant pain-related diagnosis. Comprehensive assessment for coexisting pain generators remains necessary.

In recent years, healthcare strategies have increasingly emphasized a holistic and comprehensive approach in patient management that extends beyond the treatment of isolated physical symptoms. In this context, the use of nutraceuticals has gained interest as a complementary approach, particularly in managing chronic conditions and age-related disorders, such as lower urinary tract symptoms (LUTS) due to benign prostate hyperplasia (BPH). A new dietary supplement, contains a blend of bio-active compounds (Drolessano®)-including lycopene, sulforaphane, silymarin, glutathione, escine, tryptophan, and green tea extract-has been introduced in Italian pharmacopeia as food supplements in urological and andrological diseases. Here, we aim to assess the effects of Drolessano® on serum prostate-specific antigen (PSA) levels and urinary symptoms in individuals with BPH. Fifty-five men presenting with elevated PSA values and mild lower urinary tract symptoms (International Prostate Symptom Score [IPSS] < 7) were recruited in this pilot study. All enrolled patients underwent Drolessano® one tablet daily for 6 months. PSA concentrations and IPSS scores were recorded at baseline (T0), at 3 months (T1), and at the end of the treatment period (T2). Data at the follow-up has been compared with those at baseline. Patients enrolled experienced a statistical significance average PSA declined from 4.8 to 3.7 ng/mL (p < 0.003), as well as in improvement of quality of life, tested by patient reported outcomes. The supplement was generally well tolerated, and no serious adverse effects were reported during the study period. These preliminary data suggest that Drolessano® may offer a supportive benefit in the management of BPH, particularly with respect to reducing PSA levels and improvement quality of life. Otherwise, controlled trials with larger sample sizes are needed to substantiate these findings and to better understand the underlying mechanisms of action.

Lumbar disc herniation is a common cause of low back pain leading to significant functional impairment. High-intensity, low-frequency pulsed electromagnetic field (Diamagnetic therapy) gained attention to treating several diseases. We report a 47-year-old man with severe post-traumatic low back pain radiating bilaterally to the lower limbs (VAS: 8; Douleur-Neuropathique-4: 5/10). MRI showed an annulus fibrosus fissure and a partially extruded left paramedian L4-L5 disc herniation compressing the dural sac. Pharmacological treatments (NSAIDs, corticosteroids, opioids, muscle relaxants) and physical therapy (Capacitive and resistive electric transfer therapy) provided no benefit. At presentation to our Pain Room, clinical findings included positive Lasegue at 30°, bilateral Valleix signs, paraspinal tenderness, and significant quality-of-life impairment (SF-36). The patient underwent a full course of diamagnetic therapy after providing written informed consent and following ethics committee approval. After 16 sessions (twice weekly, 20 minutes each; high-intensity fluids off/biostimulation), the VAS score decreased to 0/10 and the Douleur-Neuropathique-4 to 0/10, with MRI evidence of herniation resorption. This case illustrates that diamagnetic therapy improved the patient's clinical condition in refractory post-traumatic low disc herniation, supporting its potential as a promising noninvasive option for selected patients, although further controlled studies are required to confirm its efficacy.

Pain in children remains frequently underrecognized and undertreated despite significant advances in pediatric analgesia. The pharmacologic management of pediatric pain is challenging due to developmental differences in pharmacokinetics and pharmacodynamics, variability in drug metabolism, age-dependent responses, and the limited availability of high-quality pediatric clinical trials. This narrative review summarizes current evidence regarding the pharmacologic management of nociceptive, neuropathic, and nociplastic pain in children, integrating developmental pharmacology, efficacy data, safety considerations, and limitations of available evidence. A mechanism-based classification of pain provides a useful framework for therapeutic decision-making; however, clinical conditions often involve overlapping mechanisms requiring individualized and multidisciplinary approaches. Evidence supporting pharmacological interventions varies considerably according to pain type. Acetaminophen and NSAIDs remain the most commonly used agents for nociceptive pain, while opioids retain a role in selected cases of moderate-to-severe pain under careful monitoring. Management of neuropathic and nociplastic pain remains particularly challenging due to limited pediatric trials, frequent off-label prescribing, and reliance on extrapolation from adult populations. Future research should focus on age-specific randomized controlled trials, pharmacokinetic and pharmacogenomic variability, long-term safety outcomes, and integration of pharmacologic treatments within multimodal pain management strategies.

Background: Drug-Induced Liver Injury (DILI) is a leading cause of acute hepatic impairment. Underlying liver disease, drug–drug interactions, and multiple hepatotoxic exposures can exacerbate injury. Nutraceuticals may have hepatoprotective potential. Case Presentation: A 37-year-old woman with obesity, hypertension, and PCOS presented with epigastric pain. Two weeks prior, she had taken acetaminophen (1,000–2,000 mg/day), levonorgestrel (three days before admission), and mushrooms one day prior. Laboratory tests revealed elevated AST, ALT, γ-GT, and bilirubin. Imaging showed fatty liver and microlithiasis. DILI was diagnosed, attributed primarily to acetaminophen and methyldopa, in the context of Non-alcoholic fatty liver disease. Offending drugs were discontinued; supportive therapy included ursodeoxycholic acid, dietary modifications, and a nutraceutical formulation (Drolessano®) for 3 months. Liver enzymes peaked on day 11 but gradually improved. By day 64, AST, ALT, and γ-GT normalized, total and indirect bilirubin were normal, and direct bilirubin was slightly elevated (0.55 mg/dL). Conclusion: DILI can result from multiple interacting factors, including polypharmacy and underlying liver disease. Prompt withdrawal of hepatotoxic agents and supportive

BACKGROUND:Fluoroquinolones may have negative effects on the central nervous system; isolated dysarthria has not been thoroughly described. CASE:Piperacillin/tazobactam and high-dose levofloxacin were used to treat a severe case of Legionella pneumophila pneumonia in a 55-year-old man with diabetes and temporary renal failure who was admitted to the hospital. On the eighth day of treatment, he experienced sudden dysarthria without any additional neurological impairment. Magnetic resonance angiography and brain magnetic resonance imaging results were negative. After levofloxacin was stopped two days later and replaced with azithromycin, the patient's dysarthria completely disappeared, and he was discharged on azithromycin (500 mg for 11 days). The Naranjo score (likely adverse reaction) was 6. CONCLUSION:This case report highlights the importance of quickly identifying even mild neurological problems in fluoroquinolone-treated patients, especially when risk factors are present. In a broader sense, it upholds the concepts of patient safety and therapeutic appropriateness, which state that drugs should only be used when necessary and should be stopped immediately if they have negative side effects. In this regard, strict adherence to the current regulatory cautions about fluoroquinolones is necessary.

Background: Osteoarthritis (OA) is a heterogeneous joint disorder traditionally considered mechanically driven; however, evidence indicates that inflammatory mechanisms contribute to symptom expression. Exploratory analyses of peripheral biomarkers may provide insights into systemic inflammation in symptomatic knee OA, but formal phenotypic validation requires dedicated clustering or longitudinal studies. Objective: To examine associations between clinical pain, functional impairment, and circulating inflammatory biomarkers in patients with knee OA compared with healthy controls. Methods: In this prospective, single-center study, patients aged 40-80 years with radiographically confirmed knee OA and chronic knee pain were compared with age- and sex-matched healthy controls. Pain intensity and functional status were assessed using the Visual Analogue Scale (VAS) and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Circulating inflammatory biomarkers, including cytokines and matrix metalloproteinases, were quantified using multiplex immunoassays. Statistical analyses included adjusted linear regression models, with age and BMI as covariates, and multiple testing correction using the Benjamini-Hochberg procedure (FDR alpha error 5%). Results: OA patients exhibited higher circulating levels of TNF-α, IL-6, IL-8, MMP-1, MMP-3, TNFSF13, TNFSF13B, and pentraxin-3 compared with controls (p < 0.01). No significant sex differences were observed. KOOSs correlated with IL-6 and IL-10 levels, suggesting an association between systemic inflammatory activity and functional limitation. All findings are presented as exploratory and associative. Conclusions: Patients with knee OA display systemic inflammatory biomarker differences associated with pain and functional impairment. These results support the role of inflammation in OA symptoms within an exploratory framework. Larger, longitudinal studies are warranted to validate these observations.

INTRODUCTION:There is growing interest in identifying drug interactions between Paxlovid (nirmatrelvir/ritonavir), an antiviral drug used for the management of outpatients with mild to moderate coronavirus disease, and antiepileptic drugs. METHODS:We searched the databases PubMed, MEDLINE, Cochrane, and EMBASE from their inception until 30 May 2025, using the keywords "Paxlovid" or "nirmatrelvir/ritonavir" or "antivirals COVID-19" and then "anticonvulsants" and finally "IDDs" and "drug interaction" in combination with Boolean logic operators. RESULTS:Clinical studies have reported strong and important drug-drug interactions between nirmatrelvir/ritonavir and antiepileptic drugs. Interactions with antiepileptic drugs are bidirectional. Moderate or strong CYP3A4 inducers among antiepileptic drugs should be dose-adjusted in patients taking nirmatrelvir/ritonavir. CONCLUSION:In patients with epilepsy treated with antiepileptic drugs who also use Paxlovid (nirmatrelvir/ritonavir), therapeutic monitoring and intervention on the therapeutic concentration with dose adjustment of the antiepileptic drug is recommended.

Cissus quadrangularis (CQ) is a Vitaceae-derived medicinal plant rich in flavonoids, phytosterols, triterpenoids, vitamins, and bone-relevant minerals, conferring combined antioxidant, anti-inflammatory, phytoestrogenic, and osteoanabolic properties that modulate key pathways involved in bone remodeling. This narrative review aims to synthesize preclinical and clinical evidence on CQ as a potential adjunct in osteoporosis management. Preclinical studies demonstrate that CQ enhances osteoblast differentiation, collagen and matrix deposition, and mineralization, while inhibiting osteoclastogenesis and inflammatory osteoclastogenic cytokines, leading to improved bone microarchitecture, bone mineral density, and callus formation in fracture and estrogen-deficiency models. CQ phytobioactives have also been successfully integrated into advanced biomaterials, exosome-like vesicles, and self‑emulsifying drug delivery systems, improving bioavailability, osseointegration, and regenerative performance in critical-sized defects and implant models. Clinical data, although limited and heterogeneous, consistently indicate that CQ accelerates fracture healing, reduces bone pain, and increases functional recovery in maxillofacial and mandibular fractures, with favorable effects on serum calcium, alkaline phosphatase, and osteopontin expression and without major safety concerns based on available short-term data. In postmenopausal osteopenia, randomized trials show that 24‑week oral CQ stabilizes bone turnover markers and delays bone loss, albeit without short‑term gains in bone mineral density. CQ thus emerges as a multi-target, generally well-tolerated candidate for integrative osteoporosis care, particularly for early bone loss (i.e., osteopenia), fracture healing, and osteoprotection during antiresorptive drug holidays (i.e., temporary suspension of bisphosphonate therapy, particularly in the context of dental procedures). However, the absence of standardized formulations, small sample sizes, short follow-ups, and lack of head‑to‑head comparisons with standard anti‑osteoporotic therapies currently available underscore the need for long-term, multicenter randomized controlled studies using bioavailable, well-characterized CQ preparations.

Background/Objectives: Persistent infections are characterized by recurrent treatment failure and relapse despite apparent antibiotic susceptibility by standard testing, a clinical reality not fully explained by conventional resistance paradigms. Bacterial persister cells, genetically susceptible but phenotypically tolerant subpopulations, survive otherwise lethal antibiotic exposure through reversible physiological adaptations. This review proposes a pharmacological framework linking antimicrobial exposure, bacterial tolerance, persistence, relapse, and the emergence of antimicrobial resistance (AMR). Methods: A structured narrative review was conducted using PubMed/MEDLINE, ClinicalTrials.gov, Centers for Disease Control and Prevention (CDC), and World Health Organization/Global Antimicrobial Resistance and Use Surveillance System (WHO/GLASS) sources (inception to 19 June 2026, priority 2010-2026), following Scale for the Assessment of Narrative Review Articles (SANRA) framework principles. Results: Resistance, tolerance, and persistence are pharmacologically distinct phenotypes. Persistence occurs without minimum inhibitory concentration (MIC) elevation and is shaped by antimicrobial exposure, target-site penetration, biofilm barriers, intracellular localization, and host stress. The review operationalizes persistence prevention exposure (PPE) in relation to minimum duration for killing 99%/99.99% of cells (MDK99/MDK99.99), persister fraction, minimum biofilm eradication concentration (MBEC), and biphasic time-kill modeling. Conclusions: Antimicrobial therapy should evolve from a model centered solely on MIC suppression and killing of actively growing bacteria toward one that also includes the prevention and eradication of persister reservoirs. Persistence prevention may reduce relapse, repeated antibiotic exposure, and the evolutionary path toward stable AMR.

INTRODUCTION:Long COVID syndrome (LCS) is characterized by persistent neurological, respiratory, and systemic symptoms following SARS-CoV-2 infection, with limited effective treatments available. Viusid is an oral antioxidant and immunomodulatory formulation that may improve chronic inflammatory symptoms. This study evaluated the efficacy of Viusid in patients with LCS. METHODS:This randomized double-blind placebo-controlled clinical trial evaluated the efficacy and safety of Viusid in adults with long COVID syndrome. The primary endpoint was the change in brain fog severity at Day 210. Secondary endpoints included changes in neurological, respiratory, musculoskeletal, digestive, and general symptoms measured using a 23-symptom clinical questionnaire. RESULTS:All participants completed the study. Viusid significantly improved the primary endpoint, brain fog, compared with placebo (MD -1.23; 95% CI -2.41 to -0.005; p < 0.001). Significant improvements favoring Viusid were also observed in anxious-depressive mood (p < 0.001), sleep dis-orders (p = 0.003), fatigue (p = 0.023), dyspnea (p = 0.018), chest pain (p = 0.002), cough (p = 0.004), abdominal pain (p = 0.009), and myalgia (p = 0.025). These effects remained consistent after adjusted analyses. DISCUSSION:The intervention showed potential improvement in long COVID symptoms; however, the small sample size and observational design limit conclusions, warranting further randomized con-trolled studies. CONCLUSIONS:Viusid significantly improved multiple long COVID symptoms, particularly neurological and respiratory manifestations. These findings support its potential as a therapeutic option for long COVID and justify further confirmatory studies.

Introduction: Chronic low-grade inflammation is a recognized risk factor for several chronic diseases, including metabolic, cardiovascular, and neurodegenerative disorders. This study aimed to evaluate the effects of a new fixed nutraceutical combination as an add-on to the standard therapy in patients with basal inflammation. Methods: We conducted an observational, prospective, open-label study in patients attending the Clinical Pharmacology Operative Unit, University Magna Graecia of Catanzaro, Italy. Fifty-six patients (aged 33–86 years) were enrolled and received one tablet daily of the fixed nutraceutical combination for three months. Laboratory assessments were performed at baseline (T0), three months after the end of treatment (T1), and six months after the end of the study (T2) to evaluate blood inflammatory biomarkers and metabolic parameters. Quality of life and mood were assessed using the SF-36, Zung Self-Rating Anxiety Scale, and Zung Self-Rating Depression Scale, while adverse drug reactions (ADRs) were assessed using the Naranjo scale. Results: All patients completed the study. A time-dependent improvement in quality of life was observed (SF-36: T0, 52 ± 11; T2, 86 ± 7), along with significant reductions in anxiety and depression scores (P < 0.05). Inflammatory biomarkers decreased significantly in a time-dependent manner (P < 0.01). Liver function markers, low-density lipoprotein cholesterol, and triglycerides improved, while high-density lipoprotein cholesterol increased (P < 0.05). No ADRs were reported during the study period. Discussion: The observed clinical benefits are likely due to the synergistic anti-inflammatory and antioxidant effects of the nutraceutical components. Silymarin and glutathione may reduce oxidative stress and protect liver function, while tryptophan may improve mood and emotional well-being. Conclusions: In this cohort, nutraceutical supplementation was well tolerated and associated with improvements in liver function, lipid profile, inflammatory markers, and quality of life. These preliminary observations warrant further investigation in randomized controlled trials to confirm efficacy and clarify the underlying mechanism.

Background: The landscape of antimicrobial therapy is undergoing a profound transformation; the contemporary arsenal of antimicrobials, particularly those with extended half-lives and enhanced tissue penetration, necessitates critically reassessing these traditional paradigms. The growing emphasis on antimicrobial stewardship programs has underscored the importance of optimizing antimicrobial agents to minimize the development and spread of resistance. Shorter treatment durations, when clinically appropriate, represent a key strategy in this endeavor. Methods: This narrative review provides a comprehensive synthesis of current evidence on the duration of antimicrobial therapy, with a particular focus on the clinical and pharmacological implications of novel agents, including long-acting formulations. Results: We critically examine the pharmacokinetic and pharmacodynamic properties of these agents, evaluate the opportunities and limitations associated with treatment shortening strategies, and underscore the pivotal role of antimicrobial stewardship in optimizing therapeutic outcomes within an increasingly complex and evolving landscape. Conclusions: The future of antimicrobial therapy lies in a personalized approach, where treatment decisions are tailored to the individual patient, but detailed clinical trials are necessary to evaluate these approaches.

Chronic pain is a serious concern for the healthcare system, considering the high public expense. Many drugs, such as opioids, non-steroidal anti-inflammatory drugs, amitriptyline, duloxetine, and pregabalin, can be used considering the type of pain (nociceptive, neuropathic, or nociplastic). This is because prescription drugs have a significant negative impact on patient health and the economy, increasing the risk of drug interactions and side effects. Nutraceuticals/supplements may be useful to reduce safety issues, particularly in elderly patients. A new fixed nutraceutical formulation containing lycopene (Solanum lycopersicum), sulforaphane (Brassica oleracea), silymarin (Silybum marianum), reduced glutathione, escin (Aesculus hippocastanum), tryptophan, and green tea (Camellia sinensis) can be used to manage the pain even if its action on pain has not been proved in clinical trials. Nevertheless, the evidence of a strong anti-nociceptive effect by escin and green tea, alongside the antioxidant and anti-neuropathic pain properties of other components, may be useful as adjuvant therapy to reduce drug dosage and prescription. Additionally, patients in polytherapy may benefit from the presence of two hepatoprotective compounds, such as glutathione and silymarin. The aim of this narrative review is to evaluate the data available on both efficacy and safety of the described nutrients in the management of pain.

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