搜索结果：Drugs in context

Osteoarthritis (OA) significantly impairs mobility and quality of life, with its prevalence rising due to ageing populations. Intra-articular hyaluronic acid (HA) injections, or viscosupplementation, restore synovial fluid viscosity, enhancing lubrication and joint function. Hymovis®/Hymovis ONE®, an advanced HA-based viscosupplement, incorporates hydrophobic modifications via MO.RE. technology, forming a reversible network that enhances viscoelasticity and lubrication. Hymovis exhibits self-healing properties, retaining elasticity and viscosity under mechanical stress, and demonstrates enhanced resistance to oxidative damage and enzymatic degradation. Evidence also supports its shock absorption and lubricating efficacy, which may exceed that of some cross-linked HA products. Clinical trials confirm its effectiveness in reducing OA-related pain and improving function in the knee, shoulder and hip. Additionally, Hymovis supports meniscal healing, as evidenced by MRI, highlighting its role in conservative meniscal tear management. In sports medicine, Hymovis alleviates joint overuse injuries, reducing pain, enhancing function, and potentially delaying OA progression. Hymovis ONE, specifically indicated for mild-to-moderate knee and hip OA, offers a single-injection solution with long-term benefits. Limitations of this narrative review include a predominance of observational studies and relatively small sample sizes in some clinical trials. Nonetheless, current evidence suggests that Hymovis/Hymovis ONE represent effective intra-articular viscosupplementation options, leveraging MO.RE. technology to improve HA properties. Their clinical efficacy and safety make them valuable for OA management, meniscal injury treatment and joint health maintenance in active individuals, ultimately contributing to improved quality of life. Osteoarthritis is a common joint disease that causes pain and limits movement, especially in the knees, hips and hands. As people age or overuse their joints, such as during sports, this condition becomes more frequent. To help relieve symptoms, doctors often inject a natural substance called hyaluronic acid directly into the affected joint. This article looked at a special form of hyaluronic acid called Hymovis®, to understand how it works for joint pain and injury.What is Hymovis ® and how does it work?: Hymovis® is a hydrogel injected into the joint. It is made from low-modified hyaluronic acid using a special technology called MO.RE.® that gives it unique abilities. Unlike older treatments, Hymovis® can return to its shape after pressure, stays longer in the joint, and protects the joint from damage caused by overuse. These features help reduce pain, improve how the joint works and may slow down the progression of joint damage over time. This article summarizes results from many previously published studies about how Hymovis® works in people with joint problems. The authors examined clinical data and patient experiences to see when and how Hymovis® is most effective.Main findings from the reviewed studies include: Less pain and better movement: People with joint problems who received Hymovis® injections felt less pain and moved better. In many cases, the improvements lasted up to 1 year.Better than steroid injections:Hymovis® gave longer-lasting pain relief than steroids and had fewer side effects.Supports better quality of life:Imaging tests showed that joints treated with Hymovis® had improved structure and less inflammation, suggesting it helps protect the joint slowing down all the symptoms.Helps athletes and active people: People who are physically active, including athletes, saw improved joint function and were able to stay active longer without needing surgery.Useful for meniscus injuries: In people with meniscal tears in the knee, Hymovis® reduced pain and helped the injury heal, which could avoid the need for surgery.Two different posologies: Hymovis ONE® works with just one injection, which may be more convenient for patients who need time saving procedures. Osteoarthritis is becoming more common worldwide due to ageing and more active lifestyles. Many people need safe and effective treatments that help them move better and reduce pain without surgery. Hymovis® offers these benefits and is supported by many studies. It works in different joints and is helpful for both older adults and active individuals. Hymovis® is a modern joint injection that reduces pain, improves movement and supports joint movement. It may help people stay active and delay surgery, making it a valuable option for those living with joint problems.

Cough is a common symptom associated with many mild and severe medical conditions such as acute and chronic respiratory disorders. However, it can also be linked to extrapulmonary pathologies such as gastroesophageal reflux. Whilst often beneficial in clearing secretions, a persistent dry cough can significantly impair quality of life and necessitate pharmacological intervention. Cloperastine, a non-opioid antitussive agent with central and peripheral mechanisms of action, is widely used in clinical practice. This narrative review critically examines the pharmacological properties, clinical efficacy and safety profile of cloperastine in the management of non-productive cough across adult and paediatric populations. In preclinical studies, cloperastine demonstrated antitussive efficacy 1.9 times greater than that of codeine, without narcotic effects. Moreover, cloperastine exhibits a quarter of the antihistaminic potency of diphenhydramine, does not impair mucociliary clearance and relaxes bronchial smooth muscle. Across more than 40 clinical studies, cloperastine was consistently effective in reducing cough frequency and intensity, with typical doses of 20-60 mg/day (hydrochloride) or 10-106 mg/day (fendizoate) in adults, and 6-106 mg/day (fendizoate) or 5-400 mg/day (hydrochloride) in children, where dosing was fixed or adjusted for age or weight. The onset of action was observed as early as 20 minutes. It demonstrated superior or comparable efficacy to codeine, clobutinol, dextromethorphan, levodropropizine, butamirate and dihydrocodeine. In paediatric populations, it improved sleep quality and sputum quality. Cloperastine is a well-tolerated and effective antitussive with a rapid onset, favourable safety profile and low risk of central nervous system side-effects, supporting its role as a valuable therapeutic option for dry cough across all ages. Cough is one of the most common reasons people visit a doctor, especially when it occurs in children. Cough can be productive (clearing mucus) or dry (no mucus). Dry cough often results from viral infections but can also be linked to conditions like asthma or reflux. In many cases, particularly in viral or post-viral infections, it may persist after the infection, disrupting sleep and daily life. Many medicines are available to treat dry cough but not all are effective or suitable for all patients. Some, such as the opioid codeine, work by suppressing the brain’s cough reflex and may carry serious side effects such as drowsiness, nausea or even dependence, risks that are particularly concerning for children and older adults, who are more sensitive to such effects. Others, like levodropropizine, act only peripherally on the airways and, although safer, are considered less effective. Cloperastine is a non-opioid cough suppressant used for many years in several countries. It acts in two main ways: first, it acts on the brain’s cough centre to reduce the urge to cough; second, it has peripheral effects, such as relaxing the muscles in the airways and exerting antihistaminic effects, reducing inflammation and irritation. Unlike many older cough medicines, cloperastine does not cause sedation or dependence and preserves the lungs’ natural ability to clear mucus. In this review, we looked at more than 40 clinical studies on the use of cloperastine in adults and children with dry cough. We found strong evidence that cloperastine is effective in reducing both the intensity and frequency of cough, with benefits noticeable within 20 30 minutes of taking the medicine. It also improved sleep quality, especially when a larger dose was given in the evening. A comparison against other established molecules is also included. What sets our review apart is its separate focus on paediatric and adult data. Many medical reviews focus only on adult patients, even though cough is extremely common in children and can cause significant distress for both the child and their caregivers. In the studies we analysed, cloperastine was shown to be safe and effective in children of all ages, including infants. It reduced nighttime coughing, helped children sleep better, and improved overall recovery while side effects were rare, mild, and temporary. Similar results were achieved in adults with acute or chronic cough, even when caused by serious underlying diseases. Another advantage of cloperastine is the variety of formulations, such as syrups, drops, tablets and chewable forms. This allows doctors to tailor the treatment to the patient’s age, weight and preference, especially in children who may have difficulty swallowing pills. In conclusion, cloperastine is a well-tolerated, fast-acting and effective treatment for dry cough in both adults and children. Its unique dual mechanism, lack of sedative or narcotic effects, and favourable safety profile make it a valuable option for managing cough, particularly when symptoms interfere with daily life or sleep. Including children in the evidence base helps ensure that treatment decisions can be made with greater confidence across all age groups.

Pruritus is an early and often debilitating symptom of primary biliary cholangitis (PBC), significantly impairing quality of life through fatigue, sleep disturbance, anxiety and social withdrawal. Traditional management relies on a stepwise approach, with bile acid sequestrants as first-line therapy and rifampin, naltrexone, or sertraline for refractory cases, but these agents often provide incomplete relief and are limited by tolerability and drug-drug interaction concerns. Advances in understanding the mechanisms of cholestatic itch have expanded treatment options to include peroxisome proliferator-activated receptor (PPAR) agonists, such as seladelpar, elafibranor and bezafibrate that uniquely offer both antipruritic effects and improvement in biochemical markers of disease activity. Therapies targeting specific pruritogenic pathways now include ileal bile acid transporter (IBAT) inhibitors, one of which is now approved specifically for PBC-related pruritus, as well as κ-opioid receptor agonists, MrgprX4 antagonists, and autotaxin inhibitors. Optimal management integrates pharmacological therapy with supportive strategies, including skin care, lifestyle modifications and psychosocial support tailored to the individual patient's disease activity, symptom severity, and comorbidities. By addressing both the biological and experiential dimensions of pruritus, this comprehensive framework enables clinicians to improve symptom control and enhance overall quality of life for patients living with PBC. Emerging therapies and a mechanism-informed treatment approach offer promise for more effective, individualized care in this challenging clinical context. Primary biliary cholangitis (PBC) is a long-term liver disease that often causes severe itching (called pruritus). This itching can begin early in the disease and significantly affect daily life by disrupting sleep, causing fatigue, and contributing to anxiety or social withdrawal. Unfortunately, treatments traditionally used to manage this symptom do not work well for many patients or can cause side effects. For years, healthcare professionals have followed a step-by-step approach to treat PBC-related itching. The first option is usually medications that bind bile acids in the gut (such as cholestyramine). If these do not help, other drugs like rifampin, naltrexone or sertraline may be tried. However, these treatments are often only partly effective and may interact with other medications or cause safety concerns. Recent research has improved understanding of why itching occurs in PBC. Rather than being caused by a single factor, it appears to involve multiple pathways, including bile acids, nerve signalling and certain molecules in the blood. This has led to the development of newer treatments that target these underlying mechanisms more directly. Among the most promising newer therapies are drugs called PPAR agonists, which not only help reduce itching but also improve liver disease activity. Another class of drugs, called IBAT inhibitors (such as linerixibat and volixibat), works by reducing bile acid levels and has also shown benefit, although side effects like diarrhoea are common. Other experimental treatments, including drugs targeting opioid receptors, specific itch receptors or enzymes involved in itch signalling, are still being studied and are not yet widely available. Managing PBC-related itching often requires a personalized approach. In addition to medications, supportive strategies such as skin care, avoiding heat, wearing loose clothing, and addressing sleep or mental health issues are important. Overall, newer therapies and a better understanding of the causes of PBC-related itching are helping to improve treatment options. These advances offer hope for more effective and individualized care, ultimately improving quality of life for people living with PBC.

Allergic rhinitis is a highly prevalent inflammatory disease that significantly impairs sleep, daily functioning and quality of life, with symptoms increasingly amplified by environmental changes such as prolonged pollen seasons and urban pollution. Despite effective therapies, many patients remain poorly controlled due to delayed diagnosis, inappropriate self-selection of over-the-counter medications, limited adherence and incorrect intranasal technique. The fixed-dose intranasal combination of mometasone furoate and olopatadine addresses these gaps by uniting rapid antihistaminic, mast-cell stabilizing effects with potent, sustained anti-inflammatory activity. Clinical trials demonstrate superior improvement of nasal and ocular symptoms, faster onset of action, and favourable long-term safety compared with monotherapies. Its single-device formulation may enhance adherence and reduce inappropriate polypharmacy, offering a practical, guideline-aligned option for optimizing management of allergic rhinitis and mitigating risks associated with patient self-treatment. Allergic rhinitis (AR) is a common inflammatory condition that affects the nose and eyes, causing symptoms such as sneezing, congestion, runny nose, itching and watery eyes. It significantly impacts daily life, sleep, work, and school performance and often occurs alongside asthma. Environmental factors like pollution, climate change and longer pollen seasons are increasing both its prevalence and symptom duration. Current treatments for AR include oral antihistamines, nasal corticosteroids, leukotriene blockers and allergen immunotherapy. However, many patients do not achieve full relief due to delayed drug effects, poor adherence, incorrect nasal spray use, or reliance on over-the-counter medications without professional guidance. Self-diagnosis and self-treatment are common, which can delay proper management, worsen symptoms, and overlook related conditions like asthma. AR involves two phases of inflammation. The early phase is triggered by histamine release, causing immediate symptoms like sneezing and itching. The late phase involves other inflammatory cells and cytokines, leading to persistent congestion and swelling. Because no single medication addresses both phases fully, combining treatments is often necessary. The fixed-dose combination of mometasone furoate (MF), a potent anti-inflammatory nasal steroid, and olopatadine (OLO), a rapid-acting antihistamine, targets both phases. OLO provides quick relief from histamine-driven symptoms, while MF reduces long-term inflammation and congestion. Using a single spray simplifies treatment, improves adherence and avoids the complexity of taking multiple separate medications. Clinical trials have shown that MF/OLO effectively improves nasal and eye symptoms more than either drug alone or placebo. Benefits appear quickly, sometimes within 30 minutes, and are maintained with long-term use. The combination is safe, with low rates of mild side effects, and has minimal systemic steroid exposure. MF/OLO is particularly useful for moderate-to-severe or persistent AR, where monotherapy often fails. Addressing self-diagnosis and self-treatment is crucial. Many patients rely on over-the-counter antihistamines alone, which do not control congestion or inflammation, and often misuse nasal sprays. Educating patients, involving pharmacists and following guideline-based care can improve outcomes. MF/OLO can reduce inappropriate polypharmacy and deliver consistent relief across nasal and eye symptoms. Future AR management may become more personalized, using biomarkers, digital adherence tools, and combination therapies alongside allergen immunotherapy to optimize long-term control. In summary, allergic rhinitis is widespread, burdensome and often poorly controlled due to self-treatment and treatment gaps. The fixed-dose MF/OLO combination offers rapid, comprehensive symptom relief in a convenient single spray, addressing both early and late phases of inflammation and helping patients achieve better, more consistent disease control.

This systematic review assessed the potential effectiveness and safety of Serenoa repens (saw palmetto) for benign prostatic disorders, mainly benign prostatic hyperplasia and associated lower urinary tract symptoms. Following PRISMA guidance (PROSPERO: CRD420251032255), we searched PubMed, Cochrane and ScienceDirect for human studies from January 2020 to May 2025. Sixteen studies (>3000 participants) met criteria, including randomized trials, observational cohorts, a post hoc analysis, an open-label comparative study and a pharmacovigilance analysis. Overall, S. repens was associated with improvements in symptom severity (International Prostate Symptom Score) in several trials, with variable effects on urinary flow, post-void residual volume, and patient-reported quality of life. Signals of benefit appeared more consistently with hexanic lipidosterolic extracts and β-sitosterol-enriched preparations, and some real-world and head-to-head comparisons suggested outcomes comparable to alpha-blockers with fewer adverse events. Combination therapy, especially with the addition of alpha-blockers, showed larger symptom reductions in select populations, particularly with more pronounced baseline symptoms or prostatic inflammation. However, heterogeneity in extract formulations, dosing, study design, and outcome reporting limited cross-study comparability. Safety findings were generally favourable, with mostly mild gastrointestinal events and fewer sexual adverse effects than reported for conventional pharmacotherapies. Taken together, recent evidence supports S. repens as a potentially useful, well-tolerated option for benign prostatic hyperplasia-related symptoms - especially in certain formulations and as part of combination strategies - whilst underscoring the need for standardized, adequately powered trials to clarify which patients benefit most, optimal dosing, and durability of effects. Benign prostatic disorders (BPDs) are non-malignant diseases commonly found in ageing men. They include benign prostatic hyperplasia (BPH; where the prostate is enlarged) and prostatitis (where the prostate is inflamed). These diseases present symptoms that impair the quality of life of the affected men. They include increased urinary frequency and urgency during the day and exacerbated during the night. The total harm that these illnesses cause around the world is high and continues to rise. Current clinical treatments for BPDs range from lifestyle changes (for example, reducing caffeine and fluid intake, promoting exercise) to various pharmacological treatments and, in more severe cases, surgical procedures. Among the drugs that have beneficial effects on BPDs, there are two different groups: synthetic and natural drugs. Alpha-blockers and 5-alpha-reductase inhibitors are the most used synthetic drugs; however, although these drugs are effective, most men abandon the treatment because they have marked sexual side effects. Natural drugs include a variety of phytotherapeutic agents, with Serenoa repens being the most widely used. However, a standardized formulation or ideal dosage have not yet been established. This study determines whether Serenoa repens formulations can benefit men with BPDs in reducing their symptoms. The authors reviewed articles from several studies where Serenoa repens was used in the treatment of BPDs, either alone or in combination with other treatments. The evaluated clinical studies were published within the past 5 years in renowned international journals, and the authors revised these articles in a systematic way (with a scientific and rigorous method to summarize the evidence in the most impartial and complete way). The authors evaluated the efficacy and safety of Serenoa repens formulations, aiming to register the following parameters: symptom relief, objective urinary measures (for example, peak flow, prostate volume), and tolerability. Overall, treatment of BPDs with Serenoa repens was associated with improvements in symptom severity in most of the studies. Several studies show that Serenoa repens offers similar benefits to synthetic drugs but with a lower risk of adverse events. Combination therapy using Serenoa repens along with alpha-blockers showed several advantages. First, the beneficial effects of alpha-blockers are known to be brief, and the addition of Serenoa repens seems to prolong their duration. Second, combination therapy has shown larger symptom reductions. Finally, as Serenoa repens has been associated with significantly lower sexual side effects, it has been shown that, when administered in combination with an alpha-blocker, it can counteract those side effects — this advantage will make men more predisposed to adhering to treatment. Taken together, this review supports Serenoa repens as a potentially useful, well-tolerated option for the treatment of BPD-related symptoms, especially in combination with alpha-blockers. This review makes it clear that it is worth the effort to standardize drug formulations and dosages. Doing so would benefit patients and enable greater comparability between studies, which in turn would lead to stronger conclusions.

Recombinant human erythropoietin (rHuEpo) is widely used to treat anaemia in patients with cancer. Concerns regarding its safety arose from early experimental studies suggesting erythropoietin receptor (EpoR) expression in tumour cells and potential pro-tumorigenic effects. However, many of these findings were generated using non-specific antibodies or incomplete molecular validation, leading to uncertainty about the clinical relevance of EpoR in oncology. A structured narrative review was conducted through a PubMed/MEDLINE search (1990-2025) using predefined terms related to EpoR and cancer. Additional references were identified via citation tracking. Studies evaluating EpoR expression in tumour-derived cell lines or human tumour tissues or exploring the clinical implications of rHuEpo therapy were included. A bibliometric analysis was also performed to contextualize historical trends in publication volume. Early studies reported widespread EpoR expression in cancer models; however, most used non-validated polyclonal antibodies and lacked molecular confirmation. When more rigorous approaches were adopted, EpoR detection in tumours was inconsistent or negligible. Clinical trials reporting adverse outcomes with rHuEpo were largely conducted before current regulatory restrictions, used variable haemoglobin targets or enrolled patients who would not be eligible for treatment today. Current evidence does not support a biologically meaningful role of EpoR in solid tumours. When used within approved indications and modern safety guidance, rHuEpo has not been consistently associated with tumour progression or reduced survival. Continued methodological rigour is essential to clarify remaining uncertainties and optimize rHuEpo use in oncology. Erythropoietin (Epo) is a hormone that stimulates the production of red blood cells. In patients with cancer, anaemia (low red blood cell levels) is a frequent complication, often caused by the disease itself or by chemotherapy. To reduce the need for blood transfusions and improve quality of life, doctors commonly use synthetic forms of Epo, known as erythropoiesis-stimulating agents (ESAs).However, over the past two decades, concerns have emerged about whether these drugs might accidentally stimulate tumour growth. Some early studies suggested that cancer cells could carry receptors for Epo (called EpoR), raising the possibility that ESA treatment could promote cancer progression. These findings generated significant debate and led to stricter clinical guidelines. This review re-examines the scientific evidence behind this controversy. We found that many early studies claiming that cancer cells had many EpoR were based on unreliable laboratory methods and non-specific antibodies that produced false-positive results. When more accurate techniques are used, functional EpoR is not consistently found on most solid tumour cells.However, recent high-quality research suggests that Epo may still influence cancer biology in more complex ways. For example, Epo signalling can affect components of the tumour microenvironment – particularly immune cells such as macrophages – potentially shaping how the body responds to the tumour. It may also play a role in specific cell populations like cancer stem cells. These findings highlight that the biological interactions between Epo and tumours are context-dependent and not simply a matter of direct stimulation of cancer cell growth. Major medical societies, including ASCO, ESMO and NCCN, now recommend that ESAs should only be used in specific circumstances: for patients with chemotherapy-induced anaemia whose cancer treatment is not curative, and only when haemoglobin levels fall below 10 g/dL. The goal is to reduce transfusions and improve quality of life while avoiding unnecessary risks. When used according to current guidelines, ESA therapy remains a safe and effective option for managing cancer-related anaemia. It helps reduce fatigue and the need for blood transfusions without consistent evidence of promoting tumour progression. A balanced understanding of both the benefits and the remaining uncertainties is essential for doctors and patients to make informed decisions together.

Women in perimenopause or postmenopause experience an increased susceptibility to cardiometabolic disorders due to hormonal and physiological changes. This study assessed the effects of a multi-ingredient nutraceutical formulation (Syndrema®, Ghimas S.p.A.) on metabolic, inflammatory and anthropometric parameters in at-risk women in perimenopause. The formulation was designed to simultaneously target several components: body fat mass, insulin resistance, dyslipidaemia, glycaemic homeostasis, arterial hypertension and oxidative stress. Twenty-four women in perimenopause or postmenopause (aged 45-60 years, BMI ≥27) participated in a 90-day prospective, single-arm observational study conducted in a real-life clinical setting. They received the nutraceutical alongside an isocaloric diet and a standardized physical activity regimen. Assessments of clinical, biochemical and body composition parameters were conducted at baseline and at the 90-day follow-up. Evaluations included anthropometrics, bioelectrical impedance analysis, lipid profile, inflammatory and metabolic markers, insulin and glucose levels and haemodynamic variables. Paired t-tests were used to evaluate changes over time. After 90 days, participants showed significant reductions in body weight, body mass index, waist circumference, systolic blood pressure, low density lipoprotein cholesterol, triglycerides, C-reactive protein, homocysteine and uric acid. Bioelectrical impedance analysis indicated improved body composition with reductions in fat mass and fat mass percentage. Liver enzymes and azotaemia also declined, suggesting systemic benefits. The combination of a multi-ingredient nutraceutical and lifestyle modifications was associated with favourable changes in cardiometabolic, inflammatory and body composition parameters in women in perimenopause and postmenopause. These results support the role of early, non-pharmacological interventions in mitigating cardiometabolic risk during menopause. Further randomized controlled trials are needed to confirm efficacy and long-term outcomes. During the transition to menopause, many women experience weight gain, changes in body composition, and an increased risk of heart and metabolic diseases. These changes are often linked to higher abdominal fat, inflammation, and worsening cholesterol and blood sugar levels. Finding safe and effective strategies to reduce these risks early is therefore very important. This study looked at whether a multi-ingredient nutraceutical supplement, used together with a balanced diet and regular physical activity, could help improve body composition and cardiometabolic health in women before and after menopause. The study followed women with overweight for 90 days in a real-life clinical setting.At the beginning of the study and after 3 months, researchers measured body weight, waist circumference, body fat, blood pressure, and several blood markers related to cholesterol, inflammation and metabolism. Body composition was assessed using a non-invasive method that estimates fat mass and lean mass. After 3 months, participants showed meaningful improvements. On average, they lost weight and reduced abdominal fat, while improving their cholesterol levels and blood pressure. Markers of inflammation and cardiovascular risk also decreased. Importantly, these benefits were achieved without significant safety concerns and within a realistic lifestyle programme that participants could follow in everyday life.Overall, the results suggest that combining a nutraceutical supplement with a healthy diet and physical activity may help women during the menopausal transition improve their metabolic health and reduce future cardiovascular risk. These findings support the use of non-drug, preventive approaches and provide a basis for future, larger studies.

The COMPASS trial showed the benefits of dual pathway inhibition (DPI) in patients with atherosclerotic vascular disease. However, the characteristics of patients initiated on DPI have not been previously defined in clinical practice. This study aims to determine the clinical profile, management and outcomes of patients with coronary artery disease (CAD), peripheral artery disease (PAD) or both, initiating DPI using rivaroxaban 2.5 mg twice daily plus aspirin in clinical practice in Latin America. XATOA was an international, multicentre, prospective and single-arm registry that consecutively included adults with CAD, PAD or both, receiving DPI within 4 weeks before enrolment, according to clinical practice. Data from XATOA in Latin America are presented. A total of 311 patients were included (mean age 67.74±11.63 years, 29.6% women, 74.3% with CAD, 40.5% with PAD and 14.8% with both conditions). The most frequently reported reason for initiating DPI was the presence of existing, worsening or newly diagnosed atherothrombotic risk characteristics (74.9%). Mean follow-up was 445.2±145.7 days. The incidence of major adverse cardiovascular events, cardiovascular death, major adverse limb events, and acute or severe limb ischaemia was 1.72 (95% CI 0.63-3.75), 1.15 (95% CI 0.31-2.94), 1.15 (95% CI 0.31-2.95) and 0.57 (95% CI 0.07-2.07) per 100 patient-years, respectively. Permanent discontinuation of rivaroxaban treatment was observed in 15.8% of patients, and serious adverse events related to rivaroxaban occurred in 0.3% of patients. Although patients with DPI in Latin America presented with a high vascular risk profile, the incidence of major adverse cardiovascular events and major adverse limb events, as well as the risk of major bleeding, remained low during follow-up. These results support the use of rivaroxaban 2.5 mg twice daily combined with aspirin in this population in clinical practice. XATOA registry (NCT03746275). Many people have coronary artery disease (CAD), a disease where the arteries supplying the heart are narrowed, or peripheral artery disease (PAD), a disease where blood flow to the legs is reduced. These patients are at high risk of heart attacks, strokes or serious leg problems.Doctors often use a ‘dual pathway inhibition’ (DPI) approach to treat these patients. This involves combining a low dose of a blood thinner called rivaroxaban (2.5 mg twice daily) with aspirin.While we know this treatment works from large clinical trials, an international study (called the XATOA registry) wanted to see how it performs in everyday medical practice. Here, we report the results obtained specifically for patients in Latin America. The researchers followed 311 adults from Latin America who were prescribed the DPI treatment by their doctors. Most patients had CAD (74.3%), some had PAD (40.5%), and about 15% had both. The researchers monitored their health for over a year to see if they experienced any major health events or side effects. The study showed that, even though these patients were at high risk for vascular problems, the rates of serious events were low:Heart-related events: only a small number of patients experienced serious heart or brain problems, including heart attack, stroke or death caused by heart disease.Leg-related events: very few patients had serious leg problems caused by severe loss of blood flow to the limbs or needed amputations.Safety: the treatment was generally well tolerated. Only 0.3% of patients experienced serious side effects related to the medication. These results are important because they confirm that the combination of low-dose rivaroxaban and aspirin is both safe and effective for patients at high risk in Latin America. It provides ‘real-world’ evidence, beyond the controlled environment of a clinical trial, that this treatment helps protect patients from life-threatening heart and limb complications without causing significant safety concerns.

Non-alcoholic fatty liver disease (NAFLD) has now become a major global health concern. Lifestyle modifications are the first line of treatment; however, their effectiveness is often limited. Silymarin extracted from Silybum marianum is effective and well tolerated in patients with liver disorders. This study aimed to assess the effect of administration of silymarin along with lifestyle changes on lowering liver enzymes in patients with NAFLD and metabolic syndrome in a real-world setting. Patients enrolled in this observational study were prescribed standard of care (diet and physical exercise) and one capsule of 140 mg of silymarin thrice daily for 6 months. Laboratory tests, non-invasive tests, ultrasonography, quality of life questionnaire, lifestyle changes and safety were assessed at 3-month and 6-month visits. Of 360 patients enrolled in the study, 315 (88%) completed the study. At baseline, aspartate transaminase (AST), alanine transaminase (ALT) and gamma-glutamyl transferase (GGT) levels were elevated in 45%, 90% and 47% of patients, respectively. By end of study, 45% (148/328) of patients achieved normalization in at least one enzyme (AST: 42%, ALT: 34%, GGT: 28%), and overall, 78% of patients showed reduction in levels for at least one liver enzyme. Enzyme levels including AST, ALT, and GGT, underwent a clinically relevant decrease (>30%) in 42%, 40%, and 34% of patients, respectively. Silymarin was well tolerated with no serious side-effects. Silymarin combined with lifestyle modifications is a safe and effective treatment option for reducing and normalizing liver enzyme levels in patients with NAFLD and associated metabolic syndrome. ClinicalTrials.gov Identifier: NCT05051527. Many people today live with fat building up in their livers, a condition called NAFLD. It often shows up along with metabolic syndrome (MetS), which means having health problems such as high blood pressure, high blood sugar or extra body weight. People who have both NAFLD and MetS are at a higher risk of developing diabetes, heart issues or liver damage later in life.Doctors usually advise people to exercise more and follow a healthier diet. These changes help, but many people find them hard to maintain, or they may not see enough improvement.Silymarin, a natural extract from the milk thistle plant, has been known for its liver-protecting effects. It may calm inflammation and protect liver cells. Researchers wanted to see what would happen if people with NAFLD and MetS used silymarin alongside healthier habits. A group of 360 adults from Thailand, Malaysia and the Philippines joined the study. Everyone had NAFLD and MetS. Each person was asked to try and follow a healthier diet and add regular exercise to their routine. On top of that, they took silymarin (Legalon®) three times a day for 6 months.Every few months, doctors checked their liver enzyme levels, blood sugar, cholesterol and liver fat and how the participants felt overall. High liver enzymes usually mean the liver is irritated or under strain. When the numbers fall, it is often a sign that the liver is healing or working more smoothly. Most people started out with liver enzymes that were higher than normal. In 6 months, many of them saw improvements. In almost half the group, at least one liver enzyme went back to normal levels. About 78% saw their enzyme levels drop. AST levels improved in 42 out of 100 people, ALT levels improved in 40 out of 100 and GGT levels improved in 34 out of 100.There were also small but positive changes in blood sugar and liver tests that look at fat buildup and stiffness. Many people said they simply felt better physically and emotionally. The treatment was generally safe, and only a few side effects were reported, with everyone recovering. The number of people with NAFLD and MetS is increasing in many regions of the world. This study suggests that adding silymarin to everyday healthy habits might give the liver some extra support. It is not meant to replace diet or exercise, but it may offer a small boost, especially for people who feel their progress has slowed down. Lower liver enzyme levels are a good sign, and they often mean less inflammation and less stress on the liver. The results from this study are promising, but we still need more research to understand how silymarin might affect long-term heart health and overall metabolic health.

Immunostimulants were established many years ago to improve the capacity of the immune system to react to exogenous noxae. Immunostimulants can be synthesized in the lab or extracted from bacterial cultures. For example, bacterial lysates have been shown to have a significant effect on the number of infectious episodes, duration of fever and use of antibiotics in patients affected by recurrent respiratory tract infections. The capacity of bacterial lysates to induce the maturation of human monocyte-derived dendritic cells (DCs) has been indicated as the first and fundamental effect focused on the activation of an efficient immune response. Synthetic drugs, used in clinics in the prophylaxis of recurrent respiratory tract infections, have also been described to induce the maturation of DCs. Pidotimod, one of the most representative immunostimulant drugs, has been proposed to induce DC maturation. However, an optimal maturation of DCs is needed to achieve an efficient immune response. We evaluated the capacity of pidotimod in inducing the maturation of DCs using a prototypic bacterial lysate, Lantigen B, as a control. This maturation was detected using a monocyte-derived DC maturation assay, measured as an increase in the expression of the CD83 and CD86 and the secretion of IL-1β, IL-12 and IL-23, three pivotal cytokines for the activation of an efficient immune response. In the current experimental conditions, 10, 1 and 0.1 μg of pidotimod had no effects on DCs, whilst Lantigen B was able to induce complete maturation of DCs in vitro. Additionally, the same doses of pidotimod used in conjunction with Lantigen B also had no further effect on DC maturation induced by the bacterial lysate. These findings seem to support the concept that bacterial lysates are more effective than other synthetic immunostimulants in inducing an efficient immune response able to affect the incidence and severity of airway infections. PLAIN LANGUAGE SUMMARY: It has been claimed that chemically synthesized immunostimulants can induce the maturation of dendritic cells (DCs), thus mediating an efficient immune response suitable to control the number and the severity of respiratory tract infections. Bacterial-derived immunostimulants, obtained either by chemical or mechanical lysis, have been shown to enhance the immune system’s response against recurrent airway infections by directly promoting the activation of DCs thought specific receptors (such as the so-called pattern recognition receptors) on the cell surface. Optimal DC maturation is essential to drive an efficient and long-lasting immune response, but it is also fundamental to avoid the generation of a tolerogenic immune response, associated with a defective maturation of DC. While immunostimulants of bacterial origin, as stated in many different experiments and related references, induce complete activation of DCs, the extent of activation induced by synthetic ones seems lower, at least as described in specific literature. For this reason, the capacity of a prototypic synthetic immunostimulant to induce the maturation of monocyte-derived DCs in a well-established experimental protocol has been evaluated in vitro. The ability of pidotimod, alone or in combination with the prototypic bacterial lysate Lantigen B, to induce the maturation of DCs derived from monocytes of peripheral blood was evaluated. We not only by quantified the expression of surface markers (CD83 and CD86, widely expressed on mature DCs) but also measured the secretion of IL-1β, IL-12 and IL-23, which are soluble mediators involved in the activation of an efficient immune response. Pidotimod failed to induce the complete activation of DCs, unlike Lantigen B, which was used as positive control; notably, an additional effect of pidotimod on Lantigen B was found. These findings were observed both on the modification of the expression of CD83 and CD86, and on the secretion of IL-1β, IL-12 and IL-23. Synthetic immunostimulants, such as pidotimod, seem to trigger a less efficient immune response than do bacterial lysates. This finding could impact on the strategy used to attempt a reduction of the number and severity of acute episodes in patients with recurrent upper respiratory tract infections.

Cardio-metabolic-renal (CMR) conditions, including type 2 diabetes mellitus, cardiovascular disease and chronic kidney disease, represent some of the most pressing public health challenges of the 21st century. In recent years, sodium-glucose co-transporter 2 (SGLT2) inhibitors (SGLT2is) have emerged as promising therapeutic agents across these interconnected disease areas. In Europe, the four currently approved SGLT2is for the treatment of type 2 diabetes mellitus - dapagliflozin, empagliflozin, canagliflozin and ertugliflozin - all have demonstrated cardiovascular and renal benefits in large cardiovascular outcomes trials. Notably, empagliflozin and dapagliflozin have also received approval for the treatment of heart failure and chronic kidney disease. This narrative review provides an overview of the role of SGLT2is in the management of CMR diseases. Overall, SGLT2is have demonstrated consistent cardiovascular safety and clinically meaningful benefits in selected outcomes across CMR conditions, with variations amongst individual agents reflecting differences in trial populations, study design and approved indications. This review summarizes current evidence to support individualized therapeutic decision-making rather than comparative positioning within the class. People with type 2 diabetes mellitus often develop other serious health problems over time. These include heart disease, heart failure and chronic kidney disease. These conditions are closely linked and can worsen each other. Together, they are sometimes called cardio-metabolic-renal disease. Treating these conditions early and effectively is important to help people live longer and healthier lives. This article reviews recent evidence about a group of medicines, called sodium–glucose cotransporter 2 inhibitors, often shortened to SGLT2 inhibitors, that were first developed to lower blood sugar in people with type 2 diabetes mellitus. Over the last decade, large clinical studies have shown that they also protect the heart and kidneys, even in some people who do not have diabetes. The authors reviewed published medical studies on four SGLT2 inhibitors currently approved in Europe. They looked at how these medicines work, how effective they are, how safe they are, and whether they are good value for healthcare systems. The aim was to help doctors understand when and how to use these medicines in people with type 2 diabetes mellitus, heart failure or chronic kidney disease. All SGLT2 inhibitors lower blood sugar by helping the kidneys remove excess glucose through the urine. Beyond this effect, they also reduce body weight and blood pressure. More importantly, they lower the risk of being admitted to hospital for heart failure and slow the worsening of kidney disease.Large studies showed that some agents of this group are effective treatments for heart failure and chronic kidney disease, even in people without diabetes. These medicines reduced the risk of kidney failure, hospital stays and early death. Benefits were seen across many patient groups, including older adults and people taking multiple medications. Side effects were generally mild and manageable. The most common problems were genital infections and dehydration, which usually improved with simple treatment or dose adjustments. Serious side effects were rare. Overall, the benefits of treatment were much greater than the risks for most patients. Heart disease and kidney disease are major causes of illness, hospitalization and healthcare costs. This review shows that SGLT2 inhibitors do more than control blood sugar — they help protect vital organs, improve quality of life and may help people live longer.Using these medicines earlier in the course of disease may prevent serious complications before they occur. Studies also suggest that SGLT2 inhibitors can reduce long-term healthcare costs by delaying the need for dialysis, hospital care and other expensive treatments.In summary, SGLT2 inhibitors represent an important advance in the treatment of diabetes, heart failure and chronic kidney disease. They offer a simple, once-daily treatment that benefits the heart and kidneys, as well as blood sugar levels, making them a valuable option for many patients and an important tool for modern healthcare.

The growing population of cancer survivors has brought to light the critical challenge of cancer therapy-related cardiac dysfunction, particularly with the use of anthracyclines, HER2-targeted agents and other novel therapeutics. This review aims to support the personalized integration of cardiovascular risk management into oncology care to optimize long-term patient outcomes. We summarize the outline approaches to patient risk assessment and surveillance, and present evidence-based non-pharmacological and pharmacological strategies for cardioprotection during cancer treatment. These strategies highlight recent data supporting the emerging cardioprotective role of exercise training, as well as the use of SGLT2 inhibitors, ACE inhibitors, angiotensin receptor blockers, sacubitril/valsartan, beta-blockers, mineralocorticoid receptor antagonists, statins and dexrazoxane. We present a comprehensive synthesis emphasizing the critical role of cardio-oncology in identifying patients at high risk, understanding clinical outcomes, and implementing practical, evidence-based strategies. Our findings underscore the need for proactive cardiovascular risk management to enhance long-term care in oncology patients. Advances in cancer treatment have greatly improved survival, allowing many patients to live longer after their diagnosis. However, some anticancer therapies can unintentionally affect the heart. This condition, known as cancer therapy-related cardiac dysfunction (CTRCD), may lead to problems such as heart failure, abnormal heart rhythms or inflammation of the heart muscle. Several widely used treatments, including anthracycline chemotherapy, HER2-targeted therapies and certain immunotherapies, have been associated with an increased risk of cardiovascular complications. To address this challenge, the field of cardio-oncology has emerged, combining expertise from cardiology and oncology to protect the heart during cancer treatment. An important first step is identifying patients at a higher risk of cardiovascular complications before therapy begins, assessing factors such as age, existing heart disease and traditional cardiovascular risk factors. During treatment, heart function can be monitored using imaging tests such as echocardiography and blood biomarkers. Advanced techniques, including global longitudinal strain imaging, can detect subtle heart dysfunction earlier than traditional measures of cardiac function. Several strategies may help reduce the risk of cardiotoxicity. Regular physical activity can improve cardiovascular fitness and overall wellbeing during cancer treatment. In addition, medications commonly used for heart disease, including ACE inhibitors, beta-blockers, statins and newer drugs such as SGLT2 inhibitors, may help protect the heart. Certain agents, such as dexrazoxane, are specifically designed to prevent chemotherapy-related heart damage. Overall, early risk assessment, careful monitoring and preventive treatment can help reduce cardiac complications while allowing patients to benefit from effective cancer therapies.

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality globally. Even with significant advances in the synthesis of chemically based anti-cancer drugs, the unfavorable prognosis of the disease continues to pose a significant challenge. The most frequently encountered limitation of standard cancer treatments is drug resistance. Furthermore, newer target-specific therapies such as immunotherapy and stem cell therapy are costly enough and beyond the reach of most patients. Natural products, being affordable and less toxic, offer multi-targeted strategies to overcome drug resistance and improve therapeutic outcomes. Therefore, this study aims to investigate the therapeutic potential of glycoside compounds derived from Moringa oleifera: Niazirinin (NZR), Niazimicin A (NZA), 4-(Rhamnosyloxy) phenylacetonitrile (RPA), and Moringyne (MRG) in the context of CRC. An integrative network pharmacology strategy was used with the help of multiple databases and web tools. Glycoside compounds derived from Moringa oleifera were selected from the IMPPAT 2.0 database. Compound-target prediction was performed with Super Pred and STRING, while colorectal cancer (CRC)-associated genes were retrieved from the Gene Cards database. Overlapping genes between the compounds and CRC were determined with Venny 2.1. Protein-protein interaction (PPI) enrichment and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out with the STRING database (v12.0). Network building and identification of hub genes were carried out in Cytoscape (v3.10.3) and Cyto Hubba plugin respectively. Validation of the hub genes included mRNA expression profiling, overall survival, and tumor stage-specific analysis using GEPIA 2 webserver. Lastly, molecular docking of Moringa oleifera glycosides with the key hub CRC proteins was performed using the CB-Dock2 web server. Eleven hub genes (NFKB1, PIK3R1, PIK3CD, PIK3CB, CHUK, GRB2, NOS2, SLC2A1, ABL1, PDGFRA, and STAT1) were identified. Five major pathways, PI3K-Akt, cAMP, Ras, HIF-1 signaling, and MicroRNAs in cancer were highly enriched. Of the eleven hub genes, six (PIK3R1, NOS2, SLC2A1, ABL1, PDGFRA, and STAT1) were significantly dysregulated in colon (COAD) and rectal (READ) cancer tissues. In particular, NOS2, SLC2A1, and STAT1 were significantly upregulated, and PIK3R1, ABL1, and PDGFRA were significantly down regulated, indicating possible oncogenic and tumor-suppressive functions, respectively. Stage-specific analysis identified that expression of SLC2A1 differed significantly among pathological stages (F = 4.31, p = 0.00531), which warrants its consideration as a stage-specific prognostic biomarker. Molecular docking revealed that NOS2 and SLC2A1 exhibited high-affinity interactions with all Moringa oleifera glycosides, suggesting their potent inhibitory potential against metabolic and inflammatory targets in CRC. NOS2 and SLC2A1 emerged as key upregulated hub genes in CRC, showing strong binding affinities with all selected Moringa oleifera glycosides, demonstrating their therapeutic potential. Notably, SLC2A1 also presented stage-specific expression, highlighting its potential as a stage specific prognostic biomarker. Additionally, PDGFRA, a downregulated hub gene, demonstrated strong interactions and may serve as a tumor suppressive target modulated by these glycosides. The online version contains supplementary material available at 10.1007/s40203-025-00461-y.

Peptide hormone-based weight-loss therapeutics have gained increasing attention, driven amongst other reasons, by the clinical and commercial success of semaglutide. Their increasing accessibility raises concerns about their potential misuse in sports, especially in disciplines where weight management is decisive for athletic performance. Semaglutide has been included in the World Anti-Doping Agency's monitoring program since 2024. Given that amylin signalling is a key therapeutic target for next-generation weight-loss drugs, amylin receptor agonists such as pramlintide, cagrilintide and KBP-066 also warrant consideration as to metabolism and detection strategies in sports drug testing programs. This study aimed to characterize the metabolic profiles of pramlintide, cagrilintide and KBP-066, identify analytically suitable metabolites and develop and validate a LC-MS/MS-based detection approach. Comprehensive in vitro models, including human skin S9 fraction, kidney S9 fraction and biological fluids, were used to investigate metabolic pathways. HRMS/MS was employed to characterize metabolites and evaluate their suitability as analytical targets. For comparison, authentic post-administration rat samples were analysed for cagrilintide and respective biotransformation products. All three peptides underwent N-terminal and C-terminal degradation, yielding multiple stable metabolic products suitable as detection targets. Cagrilintide metabolites predicted from in vitro experiments were observed in authentic post administration rat plasma samples, confirming in vivo relevance. Finally, suitable preparation and detection methods were established and validated. This study provides the first systematic metabolic characterization of pramlintide, cagrilintide and KBP-066. The identified metabolites and LC-MS/MS detection approach offer a foundation for future monitoring of emerging weight-loss peptide hormone analogues in anti-doping contexts.

Virtually all patients with extensive-stage small cell lung cancer (SCLC) develop resistance to first-line platinum-based chemoimmunotherapy and experience relapse. Second-line therapy is therefore an integral part of the treatment paradigm. Evidence was reviewed for key second-line regimens recommended in major guidelines for treatment of patients with platinum-sensitive relapse (chemotherapy-free interval ≥90 days), focusing on recent prospective clinical trials and post hoc analyses. Case studies of second-line lurbinectedin are presented as examples of the current management approach to platinum-sensitive relapsed SCLC. Subject to the limitations of cross-trial comparisons, the evidence review allowed us to draw broad conclusions about the place in therapy of approved options for platinum-sensitive relapse. Platinum rechallenge is more effective and better tolerated than topotecan and is a reasonable second-line choice in suitable patients. Topotecan provides modest clinical benefit and has the potential to cause dose-limiting haematological toxicities. Cyclophosphamide-doxorubicin-vincristine combination therapy offers no clear advantages over topotecan. Efficacy outcomes with second-line lurbinectedin are similar or better than those reported with platinum rechallenge, and lurbinectedin has a more favourable safety profile and simpler administration schedule. Second-line lurbinectedin preserves platinum rechallenge for later use and may resensitize tumour cells to platinum with potential survival advantages. Lurbinectedin safety is not affected by advanced age (≥65 years). Case studies highlight objective and durable responses to second-line lurbinectedin, along with good tolerability and quality of life. Available evidence supports second-line lurbinectedin as a useful alternative to platinum rechallenge, topotecan and cyclophosphamide-doxorubicin-vincristine in patients with platinum-sensitive relapsed SCLC.

The pineal gland is a neuroendocrine gland located in the epithalamus. Primary pineal tumours are uncommon and metastatic cancer spreading to the pineal gland is even more unusual. Brain metastases from adenocarcinoma of upper gastrointestinal tract occur in less than 1.5% of patients, yet no clear data about the incidence of metastases in the pineal region are available. This study presents the case of a 73-year-old man who presented to the emergency room with neurological symptoms. MRI revealed a pathological lesion in the pineal gland with histological findings of metastasis from adenocarcinoma of gastrointestinal origin. An oesophagogastroduodenoscopy was performed and a distal lesion was found, which was biopsied and histologically defined as oesophageal adenocarcinoma. A literature search identified six articles regarding pineal metastases from oesophageal carcinoma. Our clinical case was compared to the literature cases examining, in particular, nine parameters of analysis: age, sex, histological diagnosis, timing of metastatic pineal onset, overall metastatic sites, clinical presentation, imaging features, size and specific treatment for the pineal lesion. Despite the small sample and 'niche' topic in the medical literature, some important conclusions can be drawn: pineal metastases are rare, their origin is difficult to define, they require multidisciplinary management, and they can produce neurological symptoms; consequently, they must be treated through a well-timed locoregional approach (surgical or radiotherapy). Finally, further scientific research is needed to better understand the pathological mechanisms of malignant cellular homing at the pineal level.

Chronic venous disease and lymphoedema frequently coexist, leading to significant symptom burden and impaired quality of life (QoL). Phlebotonic agents, such as diosmin, Ruscus aculeatus, Melilotus officinalis and Vitis vinifera, have demonstrated complementary anti-inflammatory, venotonic and lymphokinetic effects. However, real-world evidence on their combined use remains limited. The VIVEMA Stasis study was a retrospective observational analysis conducted in a real-world clinical setting. Adult patients with lower limb venous and/or lymphatic oedema received a 30-day treatment with a standardized formulation containing diosmin, R. aculeatus, M. officinalis and V. vinifera extracts, in addition to compression therapy. The primary endpoint was improvement in health-related QoL, assessed using the CIVIQ-14 questionnaire. Secondary endpoints included changes in symptom burden and limb circumference measurements. Fifty-one patients (mean age 54.0 years; 84.3% female) were included. After 30 days, significant improvements were observed in QoL (global CIVIQ-14 score: p<0.001), with reductions in pain, sleep disturbance and functional limitations. Objective measurements showed significant reductions in both ankle and calf circumferences (median reduction: 0.40 cm and 0.50 cm, respectively; p<0.001). Symptom burden scores improved significantly (median increase from 19.0 to 25.0; p=0.002), especially for swelling, heaviness and fatigue. No adverse events were reported. In this real-world setting, a short-term integrative treatment with a phlebotonic formulation combining diosmin, R. aculeatus, M. officinalis and V. vinifera significantly improved QoL, symptom burden and oedema in patients with chronic venous and lymphatic disease. These findings support the therapeutic potential of combined phlebotonic therapy alongside standard care.

Testosterone is a steroid hormone produced primarily in the testes in men and ovaries in women, playing crucial roles in androgenic, anabolic, and psychological functions, including muscle growth, bone formation, erythropoiesis, risk-taking, and aggression, making it important for athletes. Sports performance is linked closely to testosterone level, prompting athletes to explore legal and illegal ways to boost testosterone. This review examines testosterone physiology and legal strategies for optimizing testosterone levels in athletes, as well as their practical applications. Database search. Narrative review. Level 5. Maintaining healthy testosterone levels requires energy balance and optimal nutrition with adequate macronutrients and micronutrients, especially for athletes prone to dieting and food restriction. Testosterone boosters are marketed widely but lack strong evidence for efficacy and may pose risks. While some substances show promise, further research is needed. Sleep is critical as testosterone secretion is linked to the rapid eye movement phase, highlighting the need for proper sleep hygiene and addressing sleep disorders. Moderate-to-high intensity free-weight resistance exercises are most effective for increasing testosterone, while the effects of sexual activity remain unclear. Endocrine-disrupting chemicals can lower testosterone levels and should be avoided. While cold-water immersion may decrease testosterone, sauna bathing appears to be neutral. Radiofrequency electromagnetic radiation from modern electronic devices may harm the hypothalamic-pituitary-gonadal axis, warranting limited use. Over-the-counter analgesics, such as nonsteroidal anti-inflammatory drugs and acetaminophen, may decrease testosterone levels, suggesting cautious use. Seasonal changes in testosterone levels require further study. Testosterone-optimizing strategies excluding banned substances may aid in treating functional low testosterone or reducing harm in anabolic-androgenic steroid users. Educating athletes on safe and effective strategies to increase testosterone is crucial, with ongoing research needed to explore additional methods.Strength-of-Recommendation Taxonomy:B.

Colorectal cancer (CRC) is extremely rare in paediatrics with aggressive histopathology and advanced presentation. Whilst pembrolizumab has shown efficacy in adult microsatellite instability-high or mismatch repair deficiency CRC, paediatric data remain scarce. A 12-year- old boy with Lynch syndrome-associated CRC developed severe cardiac toxicity after initial chemotherapy. Treatment was switched to off-label pembrolizumab, resulting in a complete response after 24 cycles. Despite good tolerability, the patient developed a delayed bowel stricture at the tumour site. After surgery, there was no pathological evidence of residual adenocarcinoma. This case demonstrates the potential of pembrolizumab in paediatric CRC, highlighting the importance of molecular-guided rather than age-restricted therapy selection. Colorectal cancer (CRC) is exceptionally rare in children and adolescents. When it does occur at a young age, it is often linked to inherited genetic conditions. Lynch syndrome is one such condition, caused by inherited faults in genes responsible for correcting errors in DNA replication. Patients with Lynch syndrome carry a substantially elevated lifetime risk of developing CRC and other cancers. This article presents the case of a 12-year-old boy diagnosed with Lynch syndrome-associated CRC. Molecular analysis of his tumour revealed a profile known as microsatellite instability-high (MSI-H) and mismatch repair deficiency (dMMR). Standard chemotherapy was started but had to be discontinued after the first cycle, when the patient developed serious heart toxicity. Faced with this situation, the multidisciplinary team decided to use pembrolizumab, a monoclonal antibody targeting PD1. Pembrolizumab is approved for MSI-H/dMMR CRC in adults but was used here off-label, as no approved indication exists for children in Italy. After 24 treatment cycles, the patient achieved a complete response: all detectable tumour activity resolved, and biopsies of residual lymph nodes confirmed the absence of cancer. The treatment was generally well tolerated. However, approximately 1 year after completing immunotherapy, the patient developed a severe narrowing (stricture) of the bowel at the site where the tumour had been. This complication &#x2014; believed to result from scarring as the tumour regressed &#x2014; has been rarely described in adults following immunotherapy, but this is the first reported case in a paediatric patient. Surgical removal of the affected bowel segment was performed, and pathological examination confirmed no residual cancer. The patient remains without cancer more than 2 years later. This case carries important messages for patients and clinicians. Tumour biology &#x2014; not patient age &#x2014; should guide treatment selection for young people with CRC. Off-label immunotherapy can be considered in MSI-H/dMMR paediatric CRC when standard options are unavailable or not tolerated. Clinicians should be aware that bowel obstruction may occur as a delayed complication of successful immunotherapy, even in children. Finally, expanding access to clinical trials for paediatric oncology patients remains an urgent priority to ensure that younger patients benefit equally from advances in cancer treatment.