Almanac of Clinical Medicine

Rationale: Peripheral artery disease (PAD) is common among the elderly and increases the risk of cardiovascular events, disability and death. PAD course and outcomes depend not only on the condition of macrovasculature but also on the tissue perfusion. We have previously shown that Type 2 diabetic patients with lower extremity ischemia have significantly lower perfusion than healthy volunteers, and the ratio of basal perfusion in the arm and leg (BP1/BP3) measured by incoherent optical fluctuation flowmetry (IOFF) allows to identify hemodynamically significant stenoses. Aim: To analyze associations between perfusion parameters registered by IOFF and the severity of vascular involvement in PAD patients. Methods: This single center cross-sectional study included 38 PAD patients admitted to the Department of Vascular Surgery and Coronary Artery Disease. The arteries were assessed with duplex Doppler ultrasonography (DDU), according to the results of which the PAD severity score and ankle-brachial index (ABI) were calculated. Skin microhemodynamic parameters were recorded by IOFF. The basal perfusion on the arm (BP1), the dorsal foot surface and the toe (BP2 and BP3), the ratio BP1/BP3, local thermal hyperemia (LTH2 and LTH3) and an increase in perfusion after heating on two leg zones (LTH2-BP2, LTH3-BP3) were evaluated and expressed in perfusion units (PU). BP1, BP3, and BP1/BP3 values were additionally measured with laser Doppler flowmetry (LDF). The analysis was performed depending on the degree of arterial involvement determined by DDU for each limb separately (n = 73). There were ≥ 50% stenoses in 15 extremities (Group 1), occlusion of one of the major arteries in 42 (Group 2) and ≥ 2 occlusions in 16 lower extremities (Group 3). Results: In the groups 1, 2 and 3, the values of most parameters estimated by IOFF decreased with an increase in severity of limb lesions. As an example, the respective perfusion parameters for the big toe in the study groups were as follows: BP3 4.0 [2.0; 9.8], 2.2 [0.9; 3.7] and 1.1 [0.7; 2.6] PU (p = 0.007); LTH3 10.0 [6.4; 14.9], 5.0 [1.5; 7.8] and 2.5 [1.4; 4.5] PU (p 0.001), and LTH3-BP3 3.8 [2.6; 7.8], 2.4 [0.6; 4.3] and 1.2 [0.4; 1.5] PU (p = 0.001). The BP1/BP3 ratio in the above mentioned group increased: 1.8 [0.8; 7.7], 7.2 [3.4; 21.3] and 14.2 [6.6; 18.3] (p = 0.004), respectively. No similar trend was found for this parameter registered by LDF. There were significant correlations between the lower extremities perfusion parameters measured by IOFF and ABI, with the correlation coefficients ranging from 0.365 to 0.717 (p 0.05). Conclusion: The functional parameters of the skin microhemodynamics vary with different PAD severity. In addition, they correlate with clinical indicators of atherosclerosis. The IOFF technique can be promising as an additional quantitative method for assessment of microvascular blood flow in patients with PAD.

Ksenia A. Krasulina

Polina A. Glazkova

Alexey A. Glazkov

Darya S. Selivanova

Sergei S. Zagarov

Akhmed V. Vataev

Roman N. Larkov

Dmitry A. Rogatkin

An association between the blood perfusion parameters in foot tissues and the severity of arterial occlusion and stenosis in the lower extremities

下肢动脉闭塞和狭窄程度与足部组织血流灌注参数的相关性

We present a case of a rare lymphoproliferative disease diagnosed while differentiating between the causes of exudative-constrictive pericarditis. An 83-year old man was hospitalized with shortness of breath, edema and newly diagnosed atrial fibrillation (AF). Initially, the signs and symptoms were interpreted as manifestations of heart failure due to old myocardial infarction, arterial hypertension and AF. However, no significant systolic or diastolic dysfunction of the left ventricle and valve disease were identified and natriuretic peptide level was normal. Despite treatment, dyspnea and edema persisted, and pleural effusion (requiring drainage) and pericardial effusion increased. Repeated echocardiography showed signs of exudative-constrictive pericarditis. We consequently excluded the infectious (tuberculosis) and non-infectious (electrolyte disorders, hypothyroidism, solid tumors) etiologies of effusion. Taking into account the long-standing mediastinal lymphadenopathy (the patient had been previously examined, but the cause not identified), anemia, episodes of low-grade fever, weight loss, and polyneuropathy, a lymphoproliferative disease was suspected. Serum protein electrophoresis identified an M spike in the gamma globulin region. Immunophenotyping of peripheral blood lymphocytes and immunohistochemical examination of bone marrow confirmed the diagnosis of mantle cell lymphoma. The patient was referred for specialized treatment. At 5 months of the follow-up, the therapy was successful, the patient was stable with no cardiac complaints, no edema, and no new AF episodes. The case demonstrates the need to strictly follow differential diagnostic algorithms to identify the causes of nonspecific symptoms beyond one medical specialty.

Rostislav V. Binyakovskiy

Svetlana V. Borisovskaya

Oleg D. Zaharov

Dmitry G. Kiselev

Sergey V. Lepkov

Alexander V. Melekhov

Igor G. Nikitin

Alexander V. Salikov

Challenges in the diagnostics of mantle cell lymphoma in an elderly comorbid patient

老年共病患者套细胞淋巴瘤诊断中的挑战

Background: Insulinoma is a neuroendocrine tumor (NET), with its main clinical manifestation being the hypoglycemic syndrome. The symptoms of hypoglycemia are nonspecific, and therefore, in most cases, the diagnosis is made untimely. The Russian clinical guidelines for the diagnosis and treatment of NET suggest as a diagnostic test that the universal circulating marker of all NET, chromogranin A (CgA) be determined. However, the literature data on the sensitivity of CgA in the diagnosis of insulinoma are contradictory. Aim: To evaluate the diagnostic effectiveness of the CgA test in the diagnosis of insulinoma. Materials and methods: This was a hospital-based single-center, cross-sectional comparative (first step) and prospective non-comparative (second step) study conducted from 2016 to 2022. During the first part of the study, we determined serum CgA in 120 patients with suspected non-diabetic hypoglycemia and compared its levels in the patients with and without confirmed insulinoma (n = 87 and n = 33, respectively). During the second study step, CgA was measured in the insulinoma patients at 6 [4.0; 7.0] months after surgery. The CgA levels at baseline and post-surgery were analyzed in 74 patients (those with recurring non-diabetic hypoglycemia were excluded from the analysis). Results: In the study subjects without insulinoma, the median CgA level was 0.7 [0.5; 1.1] (range, 0.1 to 2.0) nmol/l and the difference (with Bonferroni adjustment) from its levels in the patients with insulinoma before surgery was non-significant (1.0 [0.7; 1.4], range, 0.1 to 8.5 nmol/l, р = 0.045). The CgA concentration in the insulinoma patients after surgery was 0.9 [0.7; 1.2], range, 0 to 1.9 nmol/l and significantly differed from that at baseline (1.0 [0.7; 1.4], range, 0.1 to 8.5 nmol/l, p = 0.012, Wilcoxon test). In the patients with insulinoma before surgery the CgA levels exceeding the generally accepted reference range ( 2 nmol/l) was found in 11.5% (n = 10), with its median level of 2.5 [2.3; 4.1], range 2.3 to 8.5 nmol/l. There were no significant associations between the CgA levels and localization, tumor numbers, their size and malignization grade, insulin and proinsulin values, and duration of fasting. The sensitivity and specificity of the CgA test were 12% [95% confidence interval [CI]: 6%–20%] and 100% [95% CI: 97%–100%], respectively. The prognostic value of a positive result (PVPR) was 100% [95% CI: 69%–100%] and the prognostic value of a negative result (PVNR) 30% [95% CI: 28%–32%]. Conclusion: As a diagnostic test, CgA has high specificity and prognostic value of a positive result. However, the uncertainty of the prognostic value of a negative result is unacceptably high. A special study is required to clarify the operational characteristics of CgA in insulinoma.

Marina Y. Yukina

Ekaterina A. Troshina

Nurana F. Nuralieva

Olga Y. Rebrova

Larisa V. Nikankina

Natalia G. Mokrysheva

Low sensitivity of chromogranin A in the diagnosis of insulinoma: a single-center study

胰岛素瘤诊断中嗜铬粒蛋白A的低敏感性：一项单中心研究

Chronic constipation is a global medical, social, and economic problem due to its negative impact on patients’ quality of life and increased risk of colorectal cancer, cardiovascular and cerebrovascular disorders. The gut microbiota plays an important role in the pathophysiology of constipation through its interplay with the immune system, enteral and central nervous system, representing a promising therapeutic target. Gut dysbiosis in patients with constipation is characterized by reduced relative numbers of bacteria producing lactate (Lactobacillaceae, Bifidobacteriaceae) and butyrate (Lachnospiraceae, Oscillospiraceae), as well as with increased numbers of those producing hydrogen sulfide (Desulfovibrionaceae) and methanogenic archaea (Methanobacteriaceae). The leading pathogenetic mechanism related to intestinal dysbiosis in chronic constipation, can be microbial metabolic abnormalities (metabolic dysbiosis) characterized by altered production of short-chain fatty acid, methane, hydrogen sulfide, tryptophan metabolites and by abnormal bile acid biotransformation. It has been proven that dysbiotic abnormalities of the intestinal microbiome play a role in the pathophysiology of constipation, which allows for the use of prebiotics, probiotics, and synbiotics for effective microbiome-modulating therapy in patients with chronic constipation. The proven role of dysbiotic abnormalities of the intestinal microbiome in the pathophysiology of chronic constipation determines the effectiveness of microbiome-modulating therapy (prebiotics, probiotics, synbiotics) in patients with this syndrome. Inulin is the most studied preboitic; it is a soluble food fiber that markedly contributes to the regulation of intestinal microbiota, stimulates the growth of beneficial bacteria, and production of anti-inflammatory metabolites. Inulin normalized the intestinal function in patients with chronic constipation increasing the stool frequency, softening the stool, and reducing the intestinal transit time. In addition, inulin modulates the immune response and impacts the absorption of minerals, appetite, and satiety. Treatment with probiotics is also associated with reduced intestinal transit time, compared to controls. According to a systematic review and meta-analysis of 30 randomized controlled trials, only Bifidobacterium lactis strains (but not other probiotics) significantly increase stool frequencies in chronic constipation in adults. Clinical studies have shown that the targeted probiotic Bifidobacterium lactis HN019 can significantly increase the stool frequencies in patients with low (≤ 3 per week) stool frequency up to 4.7–5.0 per week, reduce the intestinal transit time and the rate of functional gastroenterological symptoms in adults with constipation. Beyond its clinical effects, Bifidobacterium lactis HN019 leads to beneficial changes in intestinal microbiota, significantly increasing the bifidobacteria and decreasing the enterobacteria numbers. The results of trials confirm the importance of synbiotic correction of dysbiotic microbiota in all patients with constipation to increase stool frequencies and improve fecal consistency, as well as to prevent the chronic disorders associated with constipation. Synbiotics, such as a combination of Bifidobacterium lactis HN019 and inulin, with the properties of both complementary and synergic synbiotic, may have the greatest microbiome-modulating and functional potential to significantly improve clinical outcomes in patients with chronic constipation compared to probiotics or prebiotics used alone.

Margarita Y. Serkova

Elena B. Avalueva

Stanislav I. Sitkin

Chronic constipation: focus on microbiome-targeted therapies with prebiotics, probiotics, and synbiotics

慢性便秘：聚焦于益生元、益生菌和合生元微生物群靶向疗法

The irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders. However, at most, one-third of IBS patients are satisfied with the results of their treatment. A combination of pharmaceuticals or multi-target drugs should be used for the treatment to be effective due to the complexity of IBS pathophysiology. The Russian Expert Panel in gastroenterology, including functional gastrointestinal disorders, currently considered to be disorders of gut-brain interaction, at its open session has discussed the possibilities to increase the efficacy of treatment of patients with IBS with a multitargeted agent alverine citrate combined with simethicone registered under the trade name of Meteospasmyl® (Mayoly Pharma, France) and adopted the respective resolution. Based on the results of multiple experimental and clinical studies, the experts declared that the combination of alverine citrate with simethicone relieves pain through the alleviation of its main mechanisms (spasms, flatulence, visceral hypersensitivity, and inflammation), and normalizes bowel movements demonstrating the normokinetic (eukinetic) properties. All clinical effects of the combination of alverine citrate and simethicone are prolonged. Alverine citrate combined with simethicone improves patients’ quality of life, including their psychological well-being. Due to the efficacy and good safety profile, it is possible to use the combination of alverine citrate and simethicone as on-demand and ex juvantibus treatment. The combination of alverine citrate and simethicone is a single selective antispasmodic that allows for a simultaneous solution of two clinical challenges: to rid the patient of abdominal pains and to properly prepare the patient for instrumental examinations (colonoscopy, abdominal ultrasound, and radiological examination), due to a high simethicone dose and spasmolytic properties of alverine citrate. In addition, Meteospasmyl® is a single antispasmodic, which has demonstrated high efficacy and safety in a clinical study of its combination with a probiotic (Probiolog® IBS), containing the strains (Lactobacillus plantarum CECT 7484, Lactobacillus plantarum CECT 7485, and Pediococcus acidilactici CECT 7483) acting on all IBS pathogenesis steps. This is extremely important, considering the proven role of gut dysbiosis in IBS pathophysiology.

Oleg N. Minushkin

Olga V. Khlynova

Emilia P. Yakovenko

Yuri A. Kravchuk

Pavel V. Seliverstov

Elena A. Belousova

The potential for improving the efficacy of treatment for irritable bowel syndrome with a multi-target drug alverine citrate plus simethicone: The Expert Panel Statement

多靶点药物枸橼酸阿佛丁联合西甲硅油改善肠易激综合征治疗效果的潜力：专家小组声明

涉及主题	医学内科学生物病理外科遗传学心理学化学内分泌学生物化学精神科放射科免疫学疾病
出版信息	出版商: Moscow Regional Research and Clinical Institute，出版周期: ，期刊类型: journal，开源期刊: 是
基本数据	创刊年份: 2019，原创研究文献占比: 0.00%，自引率:N.A.， Gold OA占比: 0.00%
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Almanac of Clinical Medicine

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An association between the blood perfusion parameters in foot tissues and the severity of arterial occlusion and stenosis in the lower extremities

Challenges in the diagnostics of mantle cell lymphoma in an elderly comorbid patient

Low sensitivity of chromogranin A in the diagnosis of insulinoma: a single-center study

Chronic constipation: focus on microbiome-targeted therapies with prebiotics, probiotics, and synbiotics

The potential for improving the efficacy of treatment for irritable bowel syndrome with a multi-target drug alverine citrate plus simethicone: The Expert Panel Statement

An association between the blood perfusion parameters in foot tissues and the severity of arterial occlusion and stenosis in the lower extremities

Chronic constipation: focus on microbiome-targeted therapies with prebiotics, probiotics, and synbiotics

Low sensitivity of chromogranin A in the diagnosis of insulinoma: a single-center study

Challenges in the diagnostics of mantle cell lymphoma in an elderly comorbid patient

ISSN	2072-0505, 2587-9294
h-index	6