Terapevticheskii arkhiv

Aim. To highlight the relevance of gastrointestinal manifestations of cytomegalovirus infection (CMVI), to highlight the main risk factors for the development of this pathology, current trends in diagnosis and treatment.

Key points. CMVI is one of the most common opportunistic diseases, characterized by a variety of manifestations from asymptomatic to severe generalized forms affecting internal organs and body systems. The prevalence of CMVI worldwide ranges from 20 to 95%. Particular attention is paid to timely diagnosis, treatment and prevention of CMVI. The “gold standard” in the diagnosis of digestive diseases associated with CMVI is immunohistochemical examination and detection of cytomegalovirus (CMV) DNA in tissues using the polymerase chain reaction (PCR). Of undoubted interest in the diagnosis of CMV is the detection of CMV DNA in stool using digital PCR. Compared to quantitative PCR, digital PCR has higher accuracy and sensitivity. As first-line therapy, the drugs of choice are ganciclovir and valganciclovir. Maribavir has been successfully used to treat patients with CMV infection refractory to one or more previous therapies. One of the promising directions in the treatment of cytomegalovirus colitis in patients with ulcerative colitis is fecal microbiota transplantation.

Conclusion. Timely identification of risk factors for the development of CMV infection, the introduction of innovative methods and approaches in diagnosis, and the use of effective methods for treating diseases of the digestive system associated with CMV infection can improve the prognosis of the underlying disease and reduce the risk of developing urgent conditions in gastroenterology.

Aim. To define the role of clinical, endoscopic, laboratory and immunomorphological parameters in predicting the occurrence and course of colorectal cancer (CRC) in patients with diverticular disease of the colon (DDC).

Materials and methods. One hundred and seventy five people with DDC were examined, divided into 3 groups: group 1 – 85 patients with DDC; group 2 – 45 with DDC in combination with adenomatous polyps (AP); 3rd group – 45 with DDC with established CRC (I or II stage). The control group consisted of 30 practically healthy people. Patients and healthy people were examined according to a single program: clinical, laboratory, instrumental data and immunomorphological research methods [use of primary antibodies to p53 (mAb clone DO-7 product no. PA0057, Leica Biosystems, Leica Bond III) and Ki-67 (Ab16667, Abcam, UK)].

Results. Among the main complaints in patients with DDC and CRC, constipation was more common than in patients with DDC and DDC with AP (p<0.05). In patients with DDC and colorectal neoplasia, a positive reaction to occult blood in the feces was more often verified, compared with the group with DDC (p<0.05). Higher levels of glucose and cholesterol in blood plasma, as well as body mass index were found in patients with DDC with AP and CRC, compared with the DDC group (p<0.05). A higher level of expression of Ki-67 and p53 was found in patients with DDC combined with AP and CRC, compared with patients with DDC without colorectal neoplasia (p<0.05). At the same time, in patients with DDC with CRC, the expression level of Ki-67 and p53 was higher than in patients with DDC with AP (p<0.05)

Conclusion. In patients with DDC combined with AP and CRC, higher levels of glucose, plasma cholesterol, as well as body mass index were observed compared to the group of patients with DDC alone (p<0.05). Of note, the results of the determination of Ki-67 and p53 in the mucous membrane of the colon should be considered important prognostic markers for the development of CRC in patients with DDC.

Background. Medication errors can cause preventable adverse events. For example, inappropriate use of anticoagulants (AC) can result in bleeding and thromboembolic complications. Detection and analysis of AC medication errors allow to reveal deficiencies in the safety systems in healthcare organizations.

Aim. The study was aimed to develop a method of systematic detection of anticoagulant medication errors for consequent audit, analysis and development of medication safety improvement measures.

Materials and methods. The study was conducted in the multidisciplinary hospital and included 4924 patients admitted from January 2019 to December 2021 who received AC. Three laboratory triggers (international normalized ratio ≥4, serum creatinine ≥133 μmol/l, and glomerulofiltration rate <30 ml/min/1.73 m²) helped to reveal 4304 cases. Their matching with patient’s data helped to develop combined triggers. Two clinical pharmacologists reviewed all cases identified by combined triggers for checking medication errors. The trigger was considered positive when anticoagulant medication error was detected in the history selected by combined trigger.

Results. Of the 4924 patients 253 (5.3%) were selected by combined triggers. Combined trigger allowed to reduce the amount of medical health records audit by 97.3%. Medication errors were detected in 137 patients. Positive predictive value of selected combined triggers varied from 0 to 63.9%. Aggregated positive predictive value of all combined triggers amounted to 54.2%. AC medication errors were detected in 2.8% patients.

Conclusion. Method of systematic detection of AC medication errors using combined triggers in all hospitalized patients receiving AC allowed to reveal typical medication errors for consequent analysis and elaboration of measures to reduce preventable patient harm in healthcare settings.

Aim. To determine the phenotypic variants of patients with symptoms of gastroesophageal reflux disease (GERD), non-erosive reflux disease (NERD), hypersensitive esophagus (HSE), functional heartburn (FH) using 24-hour pH-impedance testing and high-resolution esophageal manometry (HSEM).

Materials and methods. Fifty-five treatment-native symptomatic patients with newly diagnosed GERD and 48 control group subjects (CG) were examined. The mean age of the subjects was 45.0 years (95% confidence interval [CI] 41.0–48.9). Patients were grouped based on typical symptoms (heartburn, belching, regurgitation, odynophagy, dysphagia), medical history, endoscopy results, and 24-hour pH-impedance testing. Patients with typical symptoms of GERD and Grade B, C, D erosive esophagitis (EE) according to the Los Angeles Classification (LA) based on endoscopy were excluded from the further study. All patients without changes in the esophageal mucosa on endoscopy or with LA grade A EE (presumably NERD) underwent 24-hour pH-impedance testing and HSEM without proton pump inhibitors. Acid exposure, acid reflux count, symptom association with reflux (with symptom index and symptom association with reflux), mean nocturnal impedance, and post-reflux swallow-induced peristaltic wave index were assessed. The structure (presence or absence of a hiatal hernia) and function (presence or absence of the lower esophageal sphincter hypotonia) of the esophagogastric junction, as well as the motor function of the thoracic esophagus, were assessed using HSEM. The results of the HSEM were interpreted according to the Chicago Classification, 3rd edition (2015).

Results. The number of acid refluxes in patients with NERD was 71.0 (95% CI 58.4–83.7), in subjects with HSE – 38.5 (95% CI 28.3–49.0), with FH – 13.0 (95% CI 6.5–18.2), in CG – 16.5 (95% CI 9.0–21.0). The average nocturnal basal impedance was 1300 ohms (95% CI 1000–1986) in patients with NERD, 1725 ohms (95% CI 1338–2261) in patients with HSE, 2760 ohms (95% CI 2453–3499) in FH, 2515 ohms (95% CI 2283–2700) in CG. The index of post-reflux swallow-induced peristaltic wave in patients with NERD was 61% (95% CI 57–71), with HSE – 85% (95% CI 82–88), with FH – 71% (95% CI 64–78), in CG – 66% (95% CI 63–69). Hiatal hernia and/or hypotonia of the LES were more common in patients with NERD (23%) than in CG (13.3%). Ineffective motility was detected in 34% of patients with NERD, in 23% of subject with FH and in 66.7% of patients with HSE.

Conclusion. The results support the hypothesis that patients with GERD symptoms represent a heterogeneous population. 24-hour pH-impedance testing and HSEM helps to differentiate endoscopically negative patients with GERD symptoms and patients with Grade A EE by LA to NERD, HSE and FH.

Aim. To evaluate the clinical and economic effectiveness of dapagliflozin in patients with chronic heart failure (CHF) with reduced left ventricular ejection fraction (HFrEF) in the Russian Federation in various subgroups of standard therapy for CHF.

Materials and methods. A clinical and economic analysis of the use of the drug dapagliflozin in addition to standard therapy was carried out in comparison with standard therapy in various subgroups of standard therapy for HFrEF using a modeling method. Cost calculations were carried out in a mathematical model adapted to the healthcare conditions of the Russian Federation by using Russian cost indicators and characteristics of the patient population.

Results. The present study demonstrates that the addition of dapagliflozin is beneficial in terms of clinical and cost-effectiveness, regardless of the initial regimen (angiotensin receptor-neprilysin inhibitors [ARNI] or angiotensin-converting enzyme inhibitors [ACEi]/angiotensin II receptor blockers [ARB]) of standard drug therapy for HFrEF and in all cases leads to an increase in life expectancy, a decrease in the number of hospitalizations and emergency visits due to CHF, as well as cardiovascular mortality. The obtained values of added value per additional year of life in all cases are significantly lower than the willingness-to-pay threshold, which indicates the clinical and economic effectiveness of the strategy of prescribing dapagliflozin as part of standard therapy for patients with HFrEF. In the case of adding dapagliflozin the values of the additional cost of an added year of life in the 3 considered standard therapy options (ARNI or ACEi/ARB, only ACEi/ARB and only ARNI) were 291,256, 279,571 and 338,374 rubles respectively. Thus, the scenario of using dapagliflozin with standard therapy, which included only ACEi/ARB, is characterized by the lowest additional cost and has the best clinical and economic characteristics. At the same time the scenario of use with standard therapy, which included only ARNI, is characterized by the highest value of the additional value of the added year of life.

Aim. To study the association of comorbidities and treatment outcomes in tuberculosis (TB) patients.

Materials and methods. A retrospective study includes all TB patients aged 18 years and older registered for treatment in Moscow in period 2021 the end of the 3rd quarter of 2022 using data of regional epidemiological TB monitoring system, a total of 3039 patients. The frequency and spectrum of comorbidities, its impact on the risk of adverse treatment outcome (ATO) and mortality using univariate and regression analysis were assessed.

Results. Comorbidities were identified in 1528 (50.3%) patients (95% confidence interval – CI 48.5–52.1); HIV infection (18.0%), chronic nonspecific lung disease (9.6%) and cardiovascular disease (8.2%) were predominant. The presence of comorbid pathology increased the odds of uneffective treatment (odds ratio – OR 2.56, 95% CI 2.22–3.03) and death (OR 2.45, 95% СI 1.67–3.59). Independent risk factors for ATO were HIV infection (OR 4.10, 95% CI 3.36–5.10), substance use (OR 2.57, 95% CI 1.70–3.66), chronic nonspecific lung disease (OR 1.39, 95% CI 1.04–1.88), diabetes mellitus (OR 1.69, 95% CI 1.15–2.48), liver pathology (OR 2.10, 95% CI 1.46–3.03), mental illness (OR 2.01, 95% CI 1.32–3.06). The death rate was 13.4%; the most significant predictors of mortality were HIV infection (OR 3.89, 95% CI 2.42–6.22) and liver disease (OR 1.90, 95% CI 1.27–2.82). A comorbidome model was constructed to assess the importance of different comorbidities for patient prognosis.

Conclusion. The presence of comorbidity (predominantly HIV infection and liver disease) is a significant risk factor for ATO and mortality in TB patients, which should be taken into account when organizing and providing TB care to comorbid patients.

Aim. To evaluate the efficacy of seven-day treatment with rabeprazole (Razo^®) 20 mg once daily in patients with NERD and esophagitis based on monitoring the results of pH-impedancemetry of the stomach and esophagus and assessment of clinical symptoms.

Materials and methods. Thirty patients with typical GERD manifestations were examined. The study included patients who underwent pH-impedancemetry, endoscopic examination, and were prescribed treatment with rabeprazole at a dose of 20 mg once a day. Clinical monitoring was performed during three visits: before treatment, after 3 days, and after 7 days of treatment. Control pH-impedancemetry was performed after 7 days of therapy. The third visit was the endpoint of the study.

Results. After 7 days of treatment, the response rate for heartburn was 86.7% in the overall group of patients with GERD, 94.4% in those with NERD, and 75.0% in patients with esophagitis stage A and B. After 7 days of therapy with rabeprazole, we registered a significant decrease in the total number of refluxes (from 88 to 54; p<0.001), the number of acid refluxes (from 53 to 22; p<0.001), the DeMeester index (from 23.81 to 7.62; p<0.001), and AET (from 7.54 to 2.01; p<0.001) in the esophagus and an increase in the median daily pH (from 1.8 to 5.4; p<0.001) and the time with pH>4 in the stomach (from 2.57 hours and 10.7% up to 12.3 hours and 51.3%; p<0.001). 7-day therapy with rabeprazole was accompanied by a significant improvement in GERD patients in all parameters of quality of life. 100% of patients with GERD rated their satisfaction with therapy as “good” and “very good”.

Conclusion. As a result of 7-day therapy of patients with NERD and esophagitis with Razo^® at a dose of 20 mg per day, an excellent clinical response was obtained, confirmed by a marked optimization of pH-impedancemetry parameters.

Barth syndrome is a rare genetic disease caused by abnormal cardiolipin metabolism, characterized by high mortality within 5 years of diagnosis due to heart failure and/or infectious complications. This article describes a clinical case of an adult patient with Barth syndrome. The peculiarities of the course of the disease are described, including the transformation of the hypertrophic type of cardiomyopathy into the hypokinetic type as the patient grew older. This article demonstrates the difficulty in selecting the optimal treatment of a patient with Barth syndrome in real clinical practice, in the absence of clearly prescribed recommendations and pathogenetic therapy.

Ferritin, an iron transport protein, is an acute phase protein of inflammation and oxidative stress (OS), a biomarker of cytolysis and ferroptosis. Inflammation, OS and iron overload are characteristic processes of the pathophysiology of aging. Human placental hydrolysates (HPHs) are promising hepatoprotective agents for anti-aging therapy. The goal of the team of authors was to systematize data on ferritin as a marker of aging and to identify peptides that counteract the aging pathophysiology, including through the regulation of iron and ferritin metabolism, in the HPH Laennec (manufactured by Japan Bioproducts). The results of basic and clinical studies confirm the above relationships and indicate that blood ferritin levels characterize the chronological and biological aging of the human body.

Diagnosis of asthma and chronic obstructive pulmonary disease (COPD) remains an actual problem in Russia. The lack of diagnostics and control of these diseases leads to serious consequences for public health and economic damage. Effective initiatives to improve the level of diagnosis and control of asthma and COPD include the organization of educational activities, instrumental methods of examination, the use of mobile offices for outreach work in remote communities and the introduction of medical information systems. The introduction of digital technologies into medical practice will help to improve the quality of medical care, increase the efficiency of medical centers, and ensure timely diagnosis and control of respiratory diseases. The introduction of modern approaches and methods in the diagnosis of asthma and COPD, active use of validated questionnaires and medical information systems will improve the quality of life of patients and reduce the risks of complications and exacerbations of diseases.

For the first time, the authors conducted a historical analysis of primary sources and identified 3 stages in the history of Russian pulmonology, naming 8 of its founders. The content is disclosed in two articles (the first one was published in No. 3 of our journal for 2024). This article tells about the second (pulmonology as an independent scientific and educational discipline within the clinic of internal diseases) and the third (as a new medical specialty) stages of the history of Russian pulmonology in the XX century.