Therapeutic archive

Over the past 40 years, nuclear medicine has grown to be the largest non-invasive diagnostic and therapeutic industry in the world, playing a pivotal role in various fields and disciplines of clinical practice and contributing to improved quality of life and patient prognosis. Over the first 20 years of the XXI century, the number of radionuclide procedures in the world has increased significantly, primarily due to innovations in radiopharmaceuticals, continuous improvement of the technical properties of equipment and the expansion of the boundaries of multimodal imaging. The review examines the historical and current trends in the development of nuclear medicine in the world and in Russia, including those related to radionuclide diagnostics, therapy and theranostics.

Aim. To detect the effect of the feature of the pulmonary vascular obstruction on the clinical manifestations of pulmonary embolism (PE).

Materials and methods. The 127 patients with PE were included in this study. PE verified with multidetector computed tomography with pulmonary angiography. Among them were 57 patients with high-risk PE, and 39 patients with intermediate-risk PE and 31 patients with low-risk PE. The pulmonary artery obstruction index and the obstruction level were determined.

Results. The mean values of the pulmonary artery obstruction index in high and intermediate risk patients were 42.5%, and in low risk patients – 12.5% (p<0.001). The trunk or main branches obstruction was in 80.7% of high-risk PE patients, the main or lobar branches obstruction – in 92.3% of intermediate-risk patients and lobar or segmental branches obstruction – in 93.5% of low-risk patients. Pulmonary infarction was detected in 89.2% of patients with the segmental branches obstruction and with another level of obstruction – in 28.0% of patients only (p<0.001).

Conclusion. The hemodynamic disorder in pulmonary embolism associate with the pulmonary artery obstruction index of more than 30%. The development of obstructive shock is associated with the pulmonary artery trunk obstruction, and the development of pulmonary infarction associated with the segmental branches obstruction.

Aim. To analyze diagnostic performance of cardiovascular magnetic resonance (CMR) in patients, presented with myocardial infarction with nonobstructed coronary arteries (MINOCA).

Materials ant methods. 46 consecutives patients presented with myocardial infarction without evidence of obstructive coronary disease on angiography between January, 1 2018 and October 1, 2019 were included in the study. All patients underwent CMR within 10 days after admission. MRI was performed on 1.5 T Magnetic Resonance Imaging (MRI) using comprehensive protocol (T2-images, Cine-CMR, late gadolinium enhancement (LGE)).

Results. CMR revealed myocardial infarction (MI) pattern in 14 patients (30.4%), myocarditis in 12 (26.1%), hypertrophic cardiomyopathy in 6 (13.1%). In 14 patients (30.4%) no LGE was observed. Notably in 2 patients without LGE features of takotsubo syndrome were noted. Mean age was significantly lower in patients with MI versus patient with non-ischemic causes of MINOCA (56.1±12.3 vs 64.6±12.8; p=0.04). ST elevation at admission frequency didn’t differ between MI and non-ischemic patients (35.7% vs 25.0%; p=0.76). However MI patients had significantly increased troponin level, 0.87 [0.22; 1.85] vs 0.22 [0.07; 0.38]; p=0.008. CMR allowed to establish the précised clinical diagnosis in 73.9% of the cases.

Conclusion. Clinical data doesn’t allow to differentiate ischemic or non-ischemic causes of MINOCA. However, CMR establish the correct diagnosis in most cases.

Aim. To study the prognostic value of determining Chromogranin A blood level in the diagnosis of PHEO.

Materials and methods. We conducted a comparative analytical study of 157 patients with suspected PHEO, statistical analysis of 24-hour urinary metanephrine and normetanephrine excretion test was performed, as well as a blood test for CrA, in groups that included patients without PHEO, with primary tumor or its recurrence, confirmed according to MSCT and/or scintigraphy with MIBG and/or the clonidine suppression test.

Results. The parameters of efficiency of these methods were calculated by groups and it was noted that the lowest sensitivity of the CrA determination method was observed in the group with recurrence of PHEO (43.8%), their exclusion from the entire sample didn’t change specificity of the method and it remained at a high level (85.45%), though sensitivity significantly increased up to 87.1%. Sensitivity of determining 24-hour urinary metanephrine excretion also increased significantly up to 96.8%, with 98.2% of specificity. The correlation between diameter of the tumor and its secretory activity was identified: small – with CrA level (rho 0.491) and strong – with total level of methylated catecholamines (rho 0.765). False positive results were more often observed in patients present with other neuroendocrine tumors (37.5%), as well as those taking proton-pump inhibitors (43.75%). The sensitivity and specificity of CrA determining method in the group of patients with methanephrins elevated within “gray zone” appeared to be 50 and 86.1%, respectively.

Conclusion. A blood test for CrA can be recommended as a confirmatory test for diagnosing PHEO in cases of questionable methylated catecholamines indicators or in cases of suspected relapse of PHEO. The use of the test as a first-line method is only possible if there is no possibility to study methylated catecholamines. When interpreting CrA level, it is necessary to take into account the conditions that may cause false-positive results.

Aim. The main aim of this study was to model the effectiveness of multiple myeloma (MM) therapy using machine learning, which was based on the analysis of various methods of MM treatment, a number of prognostic factors and their results in the daily routine clinical practice of medical centers in European countries.

Materials and methods. The present study was retrospective, non-interventional, multicenter. A structured database of MM patients provided by the Oncology Information service (O.I.s.) was used for the study. Registration took place in medical institutions in eight countries: Austria, Belgium, Switzerland, Germany, Spain, France, Greece and Great Britain.

Results. In total, 57% of men and 43% of women were analyzed in the base of 6074 patients with MM. The median age was 71 years. The median follow-up time along the lines was 387 days. High-risk cytogenetics are represented in 15% of cases. The efficacy endpoint was the best response to each line of therapy, as measured by time to death (TTD) as an indirect indicator of overall survival and time to next treatment (TTNT) as an indirect indicator of progression-free survival. The median TTD and TTNT were 730 and 399 days respectively. After a multi-step selection process, characteristics with the greatest importance for the therapy prognosis were selected: age at the beginning of therapy, line of therapy, time after MM verification, ECOG (Eastern Cooperative Oncology Group), cytogenetic risk, transplant eligibible or not, TTNT after the previous line of therapy, therapy regimen.

Discussion. To continue the study it is necessary to analyze literature data and compare with real practice. Also analysis and comparison with Russian data on the treatment of patients with MM is required.

Conclusion. The analysis of the presented data provides a basis for modeling a tool for assessing the effectiveness of MM therapy (prognosis of TTD and TTNT) for each patient, based on a number of prognostic factors and the results of routine clinical practice in various medical centers in European countries.

Aim. To assess the impact of summer heat waves on key parameters of oxidative stress in patients with coronary heart disease.

Materials and methods. We included 30 male patients aged 52±13 years with stable angina pectoris of II–III functional class with at least one coronary artery stenosis proved by angiography (ischemic group) in comparison with 10 male patients aged 48±7 years with no angiographic sings of significant coronary stenosis and without angina manifestation (non-ischemic group). The following parameters were studied: activity of superoxide dismutase (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), the level of malondialdehyde (MDA) and MDA-modified low-density lipoproteins (MDA-LDL). The analysis of indicators was performed at normal average daily temperature (daytime temperature not higher than 20°С) and after a heat wave (daytime temperature above 27°C for more than 2 consecutive days).

Results. Our study revealed the decrease of CAT and GSH-Px activities with increased activity of Cu,Zn-SOD in both groups after the heat wave. At the same time we observed accumulation of MDA and increased MDA-LDL level in both groups. Initially ischemic patients showed significantly increased level of CAT and GSH-Px activity compared to the non-ischemic group, while it was no difference in activity of Cu,Zn-SOD and MDA and MDA-LDL level. We observed significant reduce of Cu,Zn-SOD activity in ischemic patients compared to non-ischemic group with no significant differences in all other studied parameters of oxidative stress after heat wave.

Conclusion. Changes in the key parameters of oxidative stress in patients with ischemic heart disease during summer heat waves are comparable to those in patients without ischemia, however significantly greater inhibition of GSH-Px activity and significantly lower increase in Cu,Zn-SOD activity was noted. These results may indicate misregulation of free radical processes in patients with ischemic heart decease

Aim. To study the effectiveness of the combined probiotic Bifiform and the enzyme lactase in the treatment of secondary lactase deficiency (SLD).

Materials and methods. We examined 79 patients with SLD, isolated from the group of patients with post-infectious irritable bowel syndrome (IBS) with a predominance of diarrhea. The age of patients reached 27±3.5 years, women predominated by gender – 62%. Diagnosis of SLD was carried out in biopsies of the small intestine mucosa using a color rapid test. To diagnose small intestinal bacterial overgrowth (SIBO) all patients underwent lactulose breath test (LBT) during 2 hours by gas analyzer. All patients with lactase deficiency (LD) were divided into 2 groups: group 1 included 54/79 patients who received the combined probiotic Bifiform (1 capsule per day), group 2 was treated with the enzyme lactase [1 capsule (3450 ME) 3 times a day]. The effectiveness of therapy was evaluated by the dynamics of clinical symptoms, indicators of LBT and the detection of hypolactasia in biopsies of the small intestine mucosa twice, before and 2 weeks after treatment.

Results. In the group of patients with LD, as a result of 14-day therapy with the combined probiotic Bifiform, 85.2% showed positive clinical dynamics, the values of SIBO in the small intestine decreased from 58±14 to 21±9 ppm, p≤0.05, and the activity of the lactase enzyme was completely restored. In 14.8% of patients, LD was preserved against the background of persistent SIBO. In the second group of 25 patients, 84% of patients did not achieve a positive dynamics of the disease as a result of taking the lactase enzyme, and hypolactasia and changes in the lumen microflora of the small intestine were preserved after repeated examination of small intestine biopsies. Recovery of the activity of the lactase enzyme was observed in a small percentage of patients, which was 16%.

Conclusion. In 85.2% of patients, as a result of therapy with the combined probiotic Bifiform, the activity of the lactase enzyme was restored, due to the suppression of bacterial contamination in the lumen of the small intestine. Replacement therapy with the enzyme lactase only led to remission of LN in 14.2%, while in the majority – 85.8% – hypolactasia and SIBO remained. Pathogenetic therapy of LN in the adult population includes the appointment of a combined probiotic Bifiform 1 capsule 3 times a day, a course of at least 14 days. As a symptomatic therapy for LN, replacement therapy with the enzyme lactase can be prescribed.

Analysis of routine clinical practice of hypertensive patient management represents one of the important tools in the search for further ways to minimize hypertension-associated cardiovascular and renal adverse outcomes.

Aim. To compare the strategies for hypertension management and features of clinical use of I₁-imidazoline receptor (I₁-IR) agonists in the Russian Federation and other countries where the STRAIGHT (Selective imidazoline receptor agonists Treatment Recommendation and Action In Global management of HyperTension) study was conducted.

Materials and methods. It was a cross-sectional online study involving physicians of various specializations. The study was conducted from January 18 to July 1, 2019, in seven countries with a high rate of I₁-IR agonist prescription, including Russia.

Results. A total of 125 (4.5%) responders filled out the survey in the Russian Federation, which was somewhat lower than in other countries (6.8%). The participants were mostly general practitioners (54.0%) and cardiologists (42.0%), while in other countries greater diversity was seen. Most Russian physicians (83.0%) seemed to rely on national clinical guidelines in their routine practice, while in other countries the US guidelines were more popular (66.0%). The majority of responders stated that they took into account the traditional risk factors of hypertension when initiating the therapy; every second responder noted if sleep apnea was present. Awareness of I₁-IR agonists, their prescription rate and their preference were higher in Russia. The main reported benefits of I₁-IR agonists were their efficacy, including in resistant hypertension, and their metabolic effects (in Russia). Most participants preferred I₁-IR agonists as third-line therapy (65.0% in Russia vs 60.0% in other countries) and in combination with an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blockers (ARB) (55.0% in Russia vs 54.0% in other countries). Compared to responders from other countries, Russian physicians prescribe I₁-IR agonists as first-line (15.0% vs 5.0%) and second-line (48.0% vs 21.0%) therapy more often.

Conclusion. Russian physicians were the most aware of I₁-IR agonists and tended to prescribe drugs of this class for hypertension management more often, and I₁-IR agonist combination with ACEi was preferable compared to physician responders from other countries. Antihypertensive efficacy and metabolic effects were reported as the major benefits of I₁-IR agonist therapy.

Aim. To determine the clinical efficacy and safety of the sorbed probiotics Bifidobacterium bifidum 1 (5×10⁸ KОЕ) and B. bifidum 1 (5×10⁷ KОЕ) in combination with Lactobacillus plantarum 8P-А3 in the complex therapy of pneumonia caused by SARS-CoV-2 in adult patients without severe risk factors.

Materials and methods. An open, randomized prospective study included 100 patients (45 men, 55 women), aged 18 to 60 years without risk factors for severe COVID-19 with pneumonia confirmed by computed tomography, and an area of lung lesion no more than 75% (moderate forms). SARS-CoV-2 RNA in nasal and oropharyngeal swabs (RT-PCR) was detected in 72% of the participants, in the rest it was highly probable in terms of the aggregate parameters. Diagnostics of COVID-19 and its severity, the appointment of a standard examination and treatment were carried out in accordance with the Temporary Methodological Recommendations of the Ministry of Health of Russia, version 8 of 09.03.2020. This publication presents the results of using B. bifidum 1 (3 capsules twice a day for 10 days) during the peak of clinical manifestations (in a hospital).

Results. In those who received sorbed B. bifidum 1, by the 10th day of treatment, the frequency of weakness was 32% lower (RR 0.55 [95% CI 0.24–0.73], OR 0.25 [0.11–0.59]); hypoosmia/dysgeusia – by 22% (RR 0.42 [0.05–0.65], OR 0.40 [0.17–0.90]) and cough – by 24% (RR 0.39 [0.07–0.60], OR 0.38 [0.17–0.84]). B. bifidum 1 reduced the average duration of weakness by 3 days [1.1–4.9], hypoosmia/dysgeusia by 3.2 days [1.3–5.1], cough by 1.9 days [0.4–3,4], dyspnea – by 1.8 days [0.7–2.7], diarrhea – by 1.7 days [0.1–3.5]; reduced the risk of antibiotic-associated diarrhea by 20% (RR 0.77 [0.24–0.93], OR 0.18 [0.05–0.68]). Due to the deterioration of the condition and the increase in the symptoms of respiratory failure, additional treatment was required less often by 24% (p=0.005). After the end of the intervention, the frequency of virologic debridement, levels of CRP, leukocytes, lymphocytes, platelets and the degree of lung damage on computed tomography did not statistically differ in the compared groups. No side effects of B. bifidum 1 (5×10⁸ KОЕ) have been identified.

Conclusion. The use of sorbed B. bifidum 1 (5×10⁸ KОЕ) improved the well-being of patients without risk factors with moderate viral (SARS-CoV-2) pneumonia and reduced the duration of diarrheal syndrome in a short time. The safety profile of their use was high. More research is needed to clarify the anti-inflammatory effects of the sorbed probiotic.

The tachycardia-induced cardiomyopathy is a rare case of reversible heart failure and left ventricle disfunction. The diagnostic approach and treatment strategy are described in this article. Also the clinical case of heart failure compensation in the patient with left ventricle dilatation and atrial flutter after the reverse to sinus rhythm is after catheter ablation presented.

Differential diagnosis of causes of the pulmonary embolism in patients can be associated with certain difficulties and requires the exclusion of a wide range of diseases. There is a description of a clinical case of pulmonary embolism caused by verified thrombophilia. Features of tactics of management and treatment of the patient according to modern views are given.

There are presented the literature data and a description of the clinical course of the disease in isolated/predominant cardiac amyloidosis. Amyloid cardiomyopathy is the most common phenocopy of hypertrophic cardiomyopathy. The modern possibilities of non-invasive diagnostics using osteoscintigraphy for the differential diagnosis between amyloid cardiomyopathy caused by AL- and transthyretin amyloidosis are described in detail.

Cardiogenic shock is the pathology most commonly encountered by intensive care physicians. Its frequency averages 4–10% in STEMI (ST-elevation myocardial infarction) patients and 2–4% in NONSTEMI (non-ST-elevation myocardial infarction) patients. Effective shock therapy is impossible without understanding the hemodynamic mechanisms of its occurrence. Many authors emphasize that cardiac output is the most important indicator of cardiac function, which necessitates its monitoring. Meanwhile, the cardiac output monitoring is associated with a number of difficulties, including those related to the technology of recording this function. In this article, the authors emphasize the importance of measuring central hemodynamic parameters in patients with predominantly cardiogenic shock. We have tried to structure the knowledge about different techniques of central hemodynamics monitoring, considered advantages and disadvantages of each of them. We believe that the data obtained by hemodynamic monitoring should be closely studied and used, because sometimes multidirectional mechanisms may be involved in the genesis of shock; therefore, therapy should be based on the data obtained in a particular patient.

In this review, we discussed the epidemiological and pathogenetic aspects of mixed steatohepatitis (SH), developed due to non-alcoholic fatty liver disease, metabolic associated fatty liver disease, drug-induced liver injury. We discussed the mechanisms of the mutually aggravating influence of etiological factors. Drugs can cause steatosis and SH, as well as contribute to the progressive course of existing SH, primarily of metabolic origin. The issues of interaction of pathogenetic factors, peculiarities of diagnostics and perspectives of pathogenetic and symptomatic treatment are considered. Therapy of mixed SH is based on avoidance of hepatotoxic drugs and lifestyle modification, medications with demonstrated efficacy (such as ademetionine) in certain SH might be used.

The arterial pressure is an important physiological indicator. The review describes the different techniques of measurement of arterial pressure, their advantages and limitations. Moreover, it also represents a historical reference about the main stage of the development of clinical sphygmomanometrya that nowadays is a relevant method for measuring arterial pressure. The emergence and the development of devices for daily monitoring of arterial pressure and modern techniques for non-invasive arterial pressure measurement are described too.