What is already known about this topic?

1. Therapeutic drug monitoring (TDM) is a personalized medicine tool that allows the monitoring of the concentration of drugs in a patient’s biological fluids.
2. TDM is especially important for drugs with a narrow therapeutic range, where the efficacy and safety directly depend on the concentration of the drug in the blood.
3. TDM is already used for many drugs, such as immunosuppressants, antiepileptics, psychotropic drugs, and some antimicrobials.
4. Pharmacogenetic testing is an "a priori" technology of personalized medicine, while TDM is "posterior", applied during treatment.
5. TDM helps to assess patient compliance with treatment and adjust the dosage or choice of drug.

What is new in the article?

1. Discussion of new prospects for TDM for drugs such as direct oral anticoagulants, antiretroviral, anti-tuberculosis drugs, and methotrexate.
2. Emphasis is placed on the need for TDM for the following risk groups: premature infants, elderly patients with polymorbidity, patients with impaired liver and kidney function, and carriers of pharmacogenetic markers.
3. The problems of TDM implementation are discussed: lack of payment by compulsory medical insurance, high cost, lack of knowledge and lack of mention in clinical guidelines.
4. The integration of TDM into clinical guidelines, standards, and payment through compulsory medical insurance is proposed.
5. The need for educational programs for doctors on TDM, including clinical pharmacologists, laboratory diagnosticians, and other specialists is mentioned.

How can this affect clinical practice in the foreseeable future?

1. Expanding the use of TDM for a larger number of drugs and patients, especially from risk groups, will increase the effectiveness and safety of treatment.
2. The integration of TDM into clinical guidelines and standards will make it more accessible and mandatory for use in practice.
3. Payment for TDM through compulsory medical insurance will reduce the financial burden on patients and medical institutions, which will accelerate the implementation of the method.
4. Educational programs will improve the competencies of doctors in the field of TDM, which will lead to a wider and more competent use of the method.
5. The development of new methods for detecting drug concentrations in biological fluids will improve the accuracy and availability of TDM.
6. Pharmacoeconomic studies will help to justify the economic efficiency of TDM, which can contribute to its more active implementation in clinical practice.

What is already known about this topic?

1. Metabolic syndrome (MS) is a global health problem, especially in developed countries. Over the past 40 years, the incidence of MS has doubled, and now about a third of the population suffers from it.
2. Genetic mutations in genes such as MC4R, LEP, LEPR, PCSK1, ADCY3, POMC and MRAP2 are known to be associated with the development of obesity and MS. These genes are involved in the leptin-melanocortin signaling pathway, which regulates energy metabolism.
3. MS includes obesity, arterial hypertension, dyslipidemia, and insulin resistance. These conditions increase the risk of cardiovascular diseases, diabetes, and cancer.
4. Chronic inflammation and dysfunction of adipokines (e.g., leptin and adiponectin) play an important role in the development of MS.

What is new in the article?

1. The article describes in detail the role of specific genes (MC4R, LEP, LEPR, PCSK1, ADCY3, POMC, MRAP2) in the development of MS, including their impact on energy metabolism and eating behavior.
2. The article emphasizes that MS increases the risk of developing cancer, such as esophageal, gastric, colon, and other cancers. This is due to chronic inflammation, oxidative stress, and microRNA dysfunction.
3. The article focuses on the role of microRNA in the progression of cancer in patients with MS, which opens up new opportunities for the development of anti-cancer therapy.

How can this affect clinical practice in the foreseeable future?

1. Understanding the genetic factors that contribute to the development of MS can improve the early diagnosis and prevention of the disease. Doctors will be able to use genetic markers to identify patients with an increased risk.
2. Knowledge of the genetic predictors of MS will allow the development of individual approaches to treatment, considering the genetic characteristics of the patient.
3. Understanding the relationship between MS and oncogenesis may lead to the development of new strategies for the prevention and treatment of cancer in patients with MS, including the use of microRNAs as therapeutic targets.
4. Introduction of new knowledge about the genetic and molecular mechanisms of MS may help in the development of more effective methods for monitoring the condition of patients, thereby reducing the risk of complications such as cardiovascular diseases and diabetes.

What is already known about this topic?

1. Cough is a common side effect of angiotensin-converting enzyme inhibitors (ACEIs), occurring in 1.5%–11% of patients, and according to some data, up to 35%.
2. The main theory links cough with the accumulation of bradykinin and substance P in the airways due to ACE inhibition.
3. Studies have shown a connection between cough and polymorphisms of the ACE gene (I/D) and the bradykinin B2 receptor gene (BDKRB2).
4. The frequency of cough varies depending on the specific ACE inhibitor drug, as well as the ethnicity of the patient.

What is new in the article?

1. This article presents the results of genome-wide association studies (GWAS) that identified new candidate genes associated with the development of cough during ACE inhibitor use, such as CLASP1, KCNIP4, PREP, NTSR1, L3MBTL4, SRBT1, PNPT1, and PCGF3.
2. The article suggests the possibility of polygenic prediction of the risk of developing cough and discontinuing ACE inhibitors, which may help in identifying patients at increased risk.
3. The role of neurobiological and inflammatory mechanisms in the development of ACE inhibitor-associated cough is emphasized.

How may this affect clinical practice in the foreseeable future?

1. The introduction of genetic testing to identify patients at increased risk of developing cough during ACE inhibitor use may lead to a more personalized approach to treatment.
2. Physicians will be able to choose alternative drugs for patients with a high genetic risk of developing cough, which will increase adherence to treatment and reduce the frequency of therapy discontinuation.
3. The identification of patients with a low risk of cough will allow the safe administration of ACE inhibitors, which is especially important for patients with cardiovascular diseases.
4. The article contributes to the further development of pharmacogenomics, which may lead to the creation of new drugs with fewer side effects.

What is already known about this topic?

1. There is growing interest in personalized treatment approaches that consider the genetic characteristics of patients. Pharmacogenetic testing is used to select individual therapies, especially in patients with cardiovascular diseases.
2. ACE inhibitors are widely used to lower blood pressure in patients with hypertension, but their efficacy and safety may vary depending on the patient’s genetic characteristics.
3. The polymorphisms of genes associated with the renin-angiotensin-aldosterone system (RAAS) can affect the efficacy and safety of ACE inhibitors.

What is new in the article?

1. The authors summarized data from various studies to identify clinically significant correlations between gene polymorphisms and the efficacy of ACE inhibitors.
2. The article provides a detailed review of candidate genes (e.g., ACE, ACE2, AGT, AGTR1, SLCO1B1, etc.) that affect the pharmacological response to ACE inhibitors.
3. New data are presented on how specific polymorphisms (e.g., rs2106809 in the ACE2 gene) can affect the effectiveness of therapy and the risk of side effects.
4. It is emphasized that the impact of polymorphisms can vary depending on the ethnicity of the patients.

How can this affect clinical practice in the foreseeable future?

1. The introduction of pharmacogenetic testing before prescribing ACE inhibitors can help doctors select a more effective and safe therapy for each patient.
2. Taking into account the genetic characteristics of patients can reduce the incidence of unwanted side effects, such as dry cough, which often occurs when taking ACE inhibitors.
3. Genotyping can help determine the optimal dosage of drugs, which is especially important for patients with comorbid conditions and chronic diseases.
4. Based on the data obtained, new clinical guidelines can be developed that consider the genetic characteristics of patients for treating hypertension.

What is already known about this topic?

1. CRISPR-Cas9 is a revolutionary genome editing technology that provides high precision and versatility.
2. CRISPR is used for both diagnostics and therapy of various diseases, including genetic, oncological and infectious diseases.
3. CRISPR-based diagnostic platforms such as SHERLOCK and DETECTR demonstrate high sensitivity and speed of detection of pathogens and genetic mutations.
4. CRISPR is used to treat monogenic diseases such as sickle cell anemia and to modify T cells in cancer therapy.
5. Ethical and regulatory issues related to germline editing and the availability of the technology remain relevant.

What is new in the article?

1. The article discusses the latest advances in CRISPR technology, such as base editing and prime editing, which allow for more precise genetic modifications without breaking DNA.
2. New methods for delivering CRISPR components, including lipid nanoparticles and viral vectors, are discussed, improving the efficacy and safety of therapeutics.
3. The article highlights the potential of CRISPR in diagnosing infectious diseases (e.g. COVID-19) and cancer, including the use of liquid biopsies for early detection of tumors.
4. The article focuses on the need for responsible use of CRISPR, especially in the context of germline editing and ensuring equal access to the technology.

How might this impact clinical practice in the foreseeable future?

1. CRISPR platforms may become the standard for rapid and accurate detection of infections, genetic mutations, and cancer markers, allowing for earlier treatment.
2. CRISPR can be used to develop individualized treatments based on a patient’s genetic profile, especially in the treatment of cancer and genetic diseases.
3. CRISPR gene editing could lead to new therapeutic approaches for previously untreatable diseases, such as neurodegenerative disorders and chronic infections.
4. The article highlights the need to develop clear ethical and regulatory standards for the use of CRISPR, which could impact legislation and clinical protocols.
5. Improving delivery methods and reducing the cost of CRISPR therapies could make them more accessible to patients in resource-limited countries, benefiting global health.

What is already known about this topic?

1. One of the main problems in the treatment of tuberculosis (TB) is the low efficiency of chemotherapy associated with the poor tolerability of anti-tuberculosis drugs (ATDs) and their insufficient concentration in the blood serum.
2. It is known that genetic polymorphisms, especially in the genes encoding liver enzymes such as NAT2, CYP2E1, GST, UGT and ALDH, affect the metabolism of ATDs and can lead to the development of hepatotoxic reactions.
3. Hepatotoxic reactions are the most common side effect for treating tuberculosis, especially when using isoniazid and rifampicin.
4. The level of evidence for the relationship between NAT2 gene polymorphism and ATD toxicity (especially isoniazid) is estimated as 1-2B, while for other genes (CYP2E1, GST, UGT, ALDH) the level of evidence is lower (level 3).

What is new in the article?

1. This article provides an overview of current studies on the impact of genetic polymorphisms on the metabolism of anti-TB drugs, including isoniazid, rifampicin, ethambutol, moxifloxacin, levofloxacin, linezolid, bedaquiline, and delamanid.
2. The article highlights the role of gene polymorphisms (ABCB1, SLCO1B1, PXR, CAR, FOXO1) of organic substance transporters in maintaining therapeutic concentrations of anti-TB drugs and their impact on the efficacy and safety of treatment.
3. The article analyzes the levels of evidence on the impact of various genetic markers on the toxicity of anti-TB drugs, which helps to identify the most significant markers for clinical practice.
4. The article notes that pharmacogenetic markers are rarely mentioned in the instructions for the use of anti-TB drugs in different countries, except for isoniazid in the FDA registry.

How can this affect clinical practice in the foreseeable future?

1. The use of pharmacogenetic tests to determine gene polymorphisms (especially NAT2) can help personalize the dosage of anti-TB drugs, which will reduce the risk of hepatotoxic reactions and increase the effectiveness of treatment.
2. The introduction of genetic testing before the start of therapy will help identify patients with an increased risk of hepatotoxicity and adapt the treatment regimen, minimizing side effects.
3. Taking into account the genetic characteristics of patients can lead to the optimization of anti-TB drug dosages, which is especially important for patients with slow metabolism (for example, slow NAT2 acetylators).
4. The data obtained can be used to develop new clinical guidelines that consider pharmacogenetic parameters when prescribing anti-TB drugs.
5. More accurate dosing and reduced interruptions in treatment due to side effects can help reduce the development of drug resistance in the causative agent of TB.