Natural Health Products (NHPs) have long been considered a valuable therapeutic approach for the prevention and treatment of various diseases, including cancer. However, research on this topic has led to inconclusive and often controversial results. This review aims to provide a comprehensive update of the effects and mechanisms related to the use of NHPs, to describe the results of randomized clinical trials (RCTs) on their effects in cancer patients, and to critically discuss factors influencing clinical outcomes. RCTs available in the literature, even those studying the same NHP, are very heterogeneous in terms of indications, doses, route and timing of administration, and outcomes evaluated. Silymarin, ginsenoside, and vitamin E appear to be useful in attenuating adverse events related to radiotherapy or chemotherapy, and curcumin and lycopene might provide some benefit in patients with prostate cancer. Most RCTs have not clarified whether NHP supplementation provides any real benefit, while harmful effects have been shown in some cases. Overall, the available data suggest that although there is some evidence to support the benefits of NHPs in the management of cancer patients, further clinical trials with the same design are needed before their introduction into clinical practice can be considered.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is very complex and heterogeneous. If not adequately treated, RA patients are likely to manifest excess of morbidity and disability with an important impact on the quality of life. Pharmacological treatment is based on the administration of the disease-modifying antirheumatic drugs (DMARDs), subdivided into conventional synthetic (csDMARDs), targeted synthetic (tsDMARDs), and biological (bDMARDs). bDMARDs are now frequently administered in patients, both as alternative treatment and together with csDMARDs. Unfortunately, there is a therapeutic response variability both to old and new drugs. Therefore, to identify pre-therapeutic and on-treatment predictors of response is a priority. This review aims to summarize recent advances in understanding the causes of the variability in treatment response in RA, with particular attention to predictive potential of autoantibodies and DMARD pharmacogenetics. In recent years, several biomarkers have been proposed to personalize the therapy. Unfortunately, a magic bullet does not exist, as many factors concur to disease susceptibility and treatment outcomes, acting around the patient’s congenital background. Models integrating demographic, clinical, biochemical, and genetic data are needed to enhance the predictive capacity of specific factors singularly considered to optimize RA treatment in light of multidisciplinary patient management.

Heart Failure (HF) is a syndrome, which implies the existence of different phenotypes. The new categorization includes patients with preserved ejection fraction (HFpEF), mid-range EF (HFmrEF), and reduced EF (HFrEF) but the molecular mechanisms involved in these HF phenotypes have not yet been exhaustively investigated. Sirt1 plays a crucial role in biological processes strongly related to HF. This study aimed to evaluate whether Sirt1 activity was correlated with EF and other parameters in HFpEF, HFmrEF, and HFrEF. Seventy patients, HFpEF (n = 23), HFmrEF (n = 23) and HFrEF (n = 24), were enrolled at the Cardiology Unit of the University Hospital of Salerno. Sirt1 activity was measured in peripheral blood mononuclear cells (PBMCs). Angiotensin-Converting Enzyme 2 (ACE2) activity, Tumor Necrosis Factor-alpha (TNF-α) and Brain Natriuretic Peptide (BNP) levels were quantified in plasma. HFpEF showed lower Sirt1 and ACE2 activities than both HFmrEF and HFrEF (p < 0.0001), without difference compared to No HF controls. In HFmrEF and HFrEF a very strong correlation was found between Sirt1 activity and EF (r² = 0.899 and r² = 0.909, respectively), and between ACE2 activity and Sirt1 (r² = 0.801 and r² = 0.802, respectively). HFrEF showed the highest TNF-α levels without reaching statistical significance. Significant differences in BNP were found among the groups, with the highest levels in the HFrEF. Determining Sirt1 activity in PBMCs is useful to distinguish the HF patients’ phenotypes from each other, especially HFmrEF/HFrEF from HFpEF.

Data supporting the use of Tocilizumab (TCZ) in COVID-19 are contrasting and inconclusive. This meta-analysis aimed to assess TCZ effectiveness in reducing the mortality rate in COVID-19 patients. PubMed, Scopus, Embase, Cochrane, WILEY, and ClinicalTrials.gov were searched to evaluate observational studies and RCTs. The outcome was the mortality rate. Forty observational studies and seven RCTs, involving 9640 and 5556 subjects treated with Standard Therapy (ST) + TCZ or ST alone, respectively, were included. In patients treated with ST+TCZ, a higher survival (Log odds ratio = −0.41; 95% CI: −0.68 −0.14; p < 0.001) was found. Subgroups analyses were performed to better identify the possible interference of some parameters in modifying the efficacy of TCZ therapy on COVID-19 mortality. Separating observational from RCTs, no statistically significant (p = 0.70) TCZ-related reduction of mortality regarding RCTs was found, while a significant reduction (Log odds ratio = −0.52; 95% CI: −0.82 −0.22, p < 0.001) was achieved regarding the observational studies. Stratifying for the use of Invasive Mechanic Ventilation (IMV), a higher survival was found in patients treated with TCZ in the No-IMV and IMV groups (both p < 0.001), but not in the No-IMV/IMV group. Meta-regression analyses were also performed. The meta-analysis of observational studies reveals that TCZ is associated with reducing the mortality rate in both severe and critically ill patients. Although the largest RCT, RECOVERY, is in line with this result, the meta-analysis of RCTs failed to found any difference between ST + TCZ and ST. It is crucial to personalize the therapy considering the patients’ characteristics.

Highly active antiretroviral therapy has led to a significant increase in the life expectancy of people living with HIV. The trade-off is that HIV-infected patients often suffer from comorbidities that require additional treatment, increasing the risk of Drug-Drug Interactions (DDIs), the clinical relevance of which has often not been determined during registration trials of the drugs involved. Therefore, it is important to identify potential clinically relevant DDIs in order to establish the most appropriate therapeutic approaches. This review aims to summarize and analyze data from studies published over the last two decades on DDI-related adverse clinical outcomes involving anti-HIV drugs and those used to treat comorbidities. Several studies have examined the pharmacokinetics and tolerability of different drug combinations. Protease inhibitors, followed by nonnucleoside reverse transcriptase inhibitors and integrase inhibitors have been recognized as the main players in DDIs with antivirals used to control co-infection, such as Hepatitis C virus, or with drugs commonly used to treat HIV comorbidities, such as lipid-lowering agents, proton pump inhibitors and anticancer drugs. However, the studies do not seem to be consistent with regard to sample size and follow-up, the drugs involved, or the results obtained. It should be noted that most of the available studies were conducted in healthy volunteers without being replicated in patients. This hampered the assessment of the clinical burden of DDIs and, consequently, the optimal pharmacological management of people living with HIV.

Supplementation with natural compounds, referred to as Natural Health Products (NHPs), is emerging as an applicable strategy in all phases of Alzheimer’s disease (AD) management, alongside pharmacological therapy. Several studies have investigated the potential of NHPs to modulate neurochemical and inflammatory processes associated with clinical decline; however, the results remain inconclusive. To evaluate the influence of NHPs on the clinical outcomes of AD patients, a systematic review was performed by searching the PubMed, Scopus, Cochrane, and Clinical Trials.gov databases for randomized clinical trials (RCTs) exploring the effects associated with NHP supplementation for the treatment of AD. Out of the 34 RCTs analyzed, 50% reported improvements in cognitive function and reductions in neuroinflammatory markers following NHP supplementation, suggesting a potential but inconsistent therapeutic effect. The strongest evidence of benefit in AD patients was found with the use of vitamin D, selenium, and probiotics. A certain incidence of depressive disorders and delirium highlights the necessity to better evaluate the safety and tolerability of B vitamin supplements. Overall, this systematic review found mixed results regarding the use of NHPs in the management of AD. Further evidence is needed to support their use in clinical practice.