A diaphragmatic tumor mimicking gastric neoplasm: a clinical case report

The vast majority of patients with tumors arising from the diaphragm do not have any specific clinical symptoms, therefore, computed tomography (CT) and magnetic resonance imaging (MRI) are the techniques required for the diagnosis. This is particularly relevant when a pathological mass has grown to an extent producing a “mass effect” on the adjacent organs. In some cases, clinical symptoms of arise due to the local invasion of the neoplasm to the adjacent tissues or distant metastases. We present a rare clinical case of a mesenchymal diaphragmatic tumor in a 34-year-old patient. After a review of her clinical status and imaging of the abdomen, including CT and MRI, the preliminary diagnosis of the gastric neoplasm of uncertain behavior (D37.1) was made, despite the initial diagnostic assumption of the exogastric location of the mass based on MRI. After careful consideration of the diagnostic assessment results, a multidisciplinary decision was made to perform laparoscopic resection of the mass. The intraoperative finding was a tumor originating from the left diaphragmatic cupula with no involvement of the stomach. The patient's recovery was uneventful. Pathological examination revealed a solitary calcifying fibrous tumor of the diaphragm. This clinical case shows that a mass arising from the diaphragm can mimic one arising from the gastric fundus, leading to an incorrect diagnosis and subsequent inappropriate management.

Real world practice of medical treatment for moderate and severe inflammatory bowel diseases in Russian Federation, Republic of Belarus and Republic of Kazakhstan: intermediate results of the INTENT study

Background: The analysis of data obtained from real world clinical practice of management of patients with inflammatory bowel diseases (IBD) is an effective tool to improve medical care for this patient category. Studies of the kind are rare in Russia, which hinders a critical assessment of the current situation and optimization of the established approaches.Aim: To study real world practice of medical treatment of patients with moderate and severe IBD in the Russian Federation, Republic of Belarus and Republic of Kazakhstan.Materials and methods: We analyzed intermediate results from the INTENT study (NCT03532932), which is a multinational, multicenter, retrospective and prospective, non-interventional observation trial being performed in the Russian Federation, Republic of Belarus and Republic of Kazakhstan. The retrospective analysis included data from 706 patients above 18 years of age with confirmed diagnosis of moderate/severe ulcerative colitis (UC) and Crohn's disease (CD) made at least 2 years before the study entry, with acute exacerbations of the disease at the study entry or within the last 2 years. Data were collected during routine management; at the study entry the patients were treated with a standard regimen including 5-aminosalicylic acid (5-ASA) agents, glucocorticosteroids (GCS) and immunosuppressants (IS), as well as genetically engineered biological agents (GEBA).Results: Among 706 IBD patients, 465 had UC and 241 had CD. The male to female ratios in both groups were similar. Mean age of the UC patients was higher than that of the CD patients (41.8 [95% confidence interval (CI) 40.6–43.0] years vs 35.6 [95% CI 33.9–37.3] years, p = 0.0001). The same difference was noted for the mean age of disease manifestation (34.5 [95% CI 33.29–35.61] vs 29.7 [95% CI 28.03–31.3] years, p = 0.0001) and for mean duration of disease from the time of diagnosis to the study entry (7.3 [95% CI 6.77–7.9] for UC and 5.9 [95% CI 5.3–6.59] years for CD, p = 0.0027). The proportion of patients with familial history of IBD was low (3.2 and 0.8%, respectively, p = 0.0672). The number of smokers with CD was more than 2-fold higher than those with UC (11.2% vs 5%, p < 0.001). 58.1% of the patients in the UC group and 47.0% of those from the CD group were employed (р < 0.05). 36.6% of the UC patients and 56.0% of the CD patients had the legal disability status due to underlying disease (p < 0.005).The relapsing course of the disease was noted in 72.9% with UC and 60.6% with CD, while in the rest of the patients the disease had the continuous course. The degree of UC involvement corresponded to pancolitis in 58.9% of the cases, to left-sided colitis in 33.1%, and to proctitis in 8%. The distribution of CD location was as follows: ileocolitis 54.8%, terminal ileitis 23.7%, colitis 20.3%, isolated upper gastrointestinal tract involvement 1.2%. The prevalence of complicated UC was 12.9%, and that of the complicated CD 57.4% (р = 0.0001). There were no difference in the rate of extraintestinal manifestations between UC and CD (23.4 and 28.2%, respectively, p = 0.1705).UC and CD groups differed by their treatment patterns. In the UC group, 5-ASA + GCS regimens were given to 25.4% of the patients, whereas in the CD group, to 3.7% (р ≤ 0.0001). The second frequent regimens were: 5-ASA with subsequent IS ± GCS (17.9% in UC, 22.8% in CD, p = 0.1331); standard regimen (any 5-ASA agent, IS or GCS, but not GEBA) with subsequent treatment withdrawal or its reduction to GCS monotherapy (14.8% in UC, 5% in CD, р = 0.0001); 5-ASA with a subsequent combination with IS, then any tumor necrosis factor-α inhibitor (iTNF-α) as the basic treatment with continuation of 5-ASA and/or IS (22% in CD vs 13.5% in UC, р = 0.0052); treatment initiation from iTNF-α combined with any standard agent without any subsequent modification (24.1% in CD and 13.6% in UC, р = 0.0007). Less frequent the following treatment regimens were used: initial treatment with 5-ASA and subsequent iTNF-α with continuation of 5-ASA (4.5% in UC and 2.5% in CD, р = 0.2181); initial treatment with iTNF-α in combination with any standard agent with subsequent GEBA withdrawal and continuation of a standard regimen or its withdrawal (4.3% in UC and 7.5% in CD, р = 0.0812).The cumulative frequency of GEBA administration at various stages of treatment for CD (66.4%) was significantly higher than for UC (39.4%). Vedolizumab for CD was administered more frequently than for UC (10.4 and 3.4%, respectively, p = 0.0003). The analysis of habitual GCS use revealed a number of negative trends, namely, half of the IBD patients received more than 2 GCS courses within 2 years, and in some cases the number of GCS courses amounted to 5–8. Mean duration of a GCS course in most regimens for UC and CD was in the range of 91 to 209 days, which is significantly higher than the recommended treatment duration of 12 weeks (83 days).Conclusion: With a number of its demographic characteristics and clinical particulars, the study cohort of patients with IBD is compatible to global trends: the male to female ratio, mean patients’ age, young age at disease manifestation, smoking status, prevalence of extraintestinal manifestations and the location of CD. It is of note that 5-ASA is included into almost all treatment regimens for CD, which does not meet the treatment strategy recommended in the guidelines. Frequent administration and long duration of GCS therapy also is in contradiction with the guidelines. Of significant concern is rather rare and late administration of GEBA, especially for UC. We believe that the identified pitfalls are associated both with low awareness of doctors on the current strategies of IBD management and with low patients' compliance to treatment.

Immunological aspects of determination of an adequate biological treatment sequence for inflammatory bowel diseases: the expert board statement (St. Petersburg, May 22, 2021)

On May 22, 2021, the Expert Board met in St. Petersburg to discuss their position on immunological aspects of determination of an adequate biological treatment sequence for inflammatory bowel diseases (IBD). The Expert Board aimed at discussion of current strategies, development of a consensus on determination of an adequate biological treatment sequence for IBD. The main topics of the agenda were the contribution of immune system to the pathophysiology of Crohn's disease, ulcerative colitis and their complications, efficacy of genetically engineered biological agents (GEBA) at various stages of IBD management. Participation of the leading Russian experts in IBD, as well as involvement of other specialties, made it possible to consider the topic by a multidisciplinary team, with an in-depth analysis of IBD pathophysiology, to better understand the course of the disease in some contradictory situation, for instance, when clinical remission is not associated with an endoscopically confirmed remission. One of the expected effects of this Expert Board meeting would be an improvement of GEBA administration in clinical practice, mostly due to the modification of clinical guidelines. This would ascertain and confirm the algorithms for GEBA administration for IBD, including the optimal treatment sequence depending on an agent’s mechanism of action and the patient profile. The clarification of the optimal GEBA sequence in the clinical guidelines could lead to more frequent GEBA administration in local medical clinics and institutions in the regions, where GEBA are used insufficiently due to little experience and absence of their precise positioning in the clinical guidelines.

Preoperative mechanical bowel preparation combined with oral antibacterials in the prevention of complications of surgery for rectal and rectosigmoid junction cancer

Aim: To evaluate the efficacy of mechanical bowel preparation (MBP) combined with oral antibacterials for the prevention of postoperative complications when preparing a patient for anterior rectal resection.Materials and methods: We analyzed shortterm results in 77 patients who had undergone anterior rectal resection for rectal and rectosigmoid junction cancer. Forty five (45) patients were prepared for surgery only with MBP. In 32 patients, in addition to MBP, oral antibacterial agents ciprofloxacin and metronidazole were used preoperatively.Results: The overall rate of postoperative complications was 6.25% (2/32 patients) in the group of combined preparation for surgery and 15.5% (7/45) in the group using only MBP. Surgical wound infection occurred in 1 patient in the combined preparation group and in 4 patients in the MBP only group. There was no anastomotic leak in the combined preparation group, whereas in the MBP only group, anastomotic leak occurred in 2 patients.Conclusion: Combined use of oral antibacterials and MBP before anterior rectal resection makes it possible to achieve an extremely low rate of the colorectal anastomosis leak. Further studies into the efficacy of this preparation regimen are needed, along with their discussion in the professional communities.

Atomic force microscopy in the assessment of erythrocyte membrane mechanical properties with exposure to various physicochemical agents

Background: Mechanical properties of cell membranes and their structural organization are considered among the most important biological parameters affecting the functional state of the cell. Under the influence of various pathogenic factors, erythrocyte membranes lose their elasticity. The resulting changes in their biomechanical characteristics is an important, but poorly studied topic. It is of interest to study the deformation of native erythrocytes to a depth compatible with their deformation in the bloodstream.Aim: To investigate the patterns of deep deformation and the particulars of structural organization of native erythrocyte membranes before and after their exposure to physicochemical agents in vitro.Materials and methods: Cell morphology, nanostructure characteristics, and membrane deformation of native erythrocytes in a solution of hemoconservative CPD/SAGM were studied with atomic force microscope NTEGRA Prima. Hemin, zinc ions (Zn2+), and ultraviolet (UV) radiation were used as modifiers. To characterize the membrane stiffness, we measured the force curves F(h), hHz (the depth to which the probe immersion is described by interaction with a homogeneous medium), and the Young's modulus values of the erythrocyte membrane.Results: Exposure to hemin, Zn2+ and UV radiation led to transformation of the cell shape, appearance of topological defects and changes in mechanical characteristics of erythrocyte membranes. Under exposure to hemin, Young's modulus increased from 10±4 kPa to 27.2±8.6 kPa (p<0.001), exposure to Zn2+, to 21.4±8.7 kPa (p=0.002), and UV, to 18.8±5.6 kPa (p=0.001). The hHz value was 815±210 nm for the control image and decreased under exposure to hemin to 420±80 nm (p<0.001), Zn2+, to 370±90 nm (p<0.001), and UV, to 614±120 nm (p=0.001).Conclusion: The results obtained contribute to a deeper understanding of interaction between membrane surfaces of native erythrocytes and small vessel walls. They can be useful in clinical medicine as additional characteristics for assessment of the quality of packed red blood cells, as well as serve as a basis for biophysical studies into the mechanisms of action of oxidative processes of various origins.

Comparison of modulation interference microscopy, DNA spectrometry, DNA cytometry, and flow cytofluorimetry in the assessment of phytohemagglutinin-induced activity of human blood lymphocytes

Rationale: The study of the structural particulars and functional state of immune cells and primarily lymphocytes is of great importance for both fundamental and clinical medicine. It requires the development of simple and reliable analytic methods that would allow for fast and effective real-time assessment of cell activity.Aim: To evaluate the effectiveness of the interference microscopy compared to DNA spectrometry, DNA cytometry, and flow cytometry with an internalized fluorescent label CFSE (carboxyfluorescein succinimidyl ester) in the assessment of PHA-induced proliferation of human blood lymphocytes.Materials and methods: Phytohemagglutinin (PHA)-induced proliferative activity of blood lymphocytes from 10 healthy volunteers was studied with various methodological strategies. Blast transformation of lymphocytes was induced by their incubation for 5 days with PHA 5 μg/mL. The cell proliferative activity was assessed as follows: 1) by DNA spectrometry at 260/280 nm using Tecan Infinite 200 Pro with a specialized NanoQuant Plate™; 2) by cytophotometry followed by cell distribution analysis assessing deoxyribonucleic acid (DNA) content after staining with Felgen's dye with an imaging system based on an Olympus BX41 light microscope with a ProgRes CF camera; 3) by flow cytometry using an internalized fluorescent label CFSE; the analysis was performed with a BD FACS Calibur flow cytometer; 4) by measurement of the lymphocyte interference profile with a modulation interference microscope MIM-340 (Schwabe, Russia). The functional activity of the nucleus (FAN) was determined and used as a criterion for assessment of the lymphocyte functional state.Results: Incubation of lymphocytes with PHA led to an increase in the linear size by 22.2±2.8%, a decrease in phase height by 46.3±4.7% (p=0.019), and an increase in FAN by 75.9±9.4%, vs control (p=0.046). As measured by isolated DNA spectroscopy, PHA stimulation of lymphocytes was associated with an increase in the amount of DNA by 55% vs baseline (409.8±22.3 ng/μL and 264.3±25.0 ng/μL, respectively, p=0.049). Felgen's reaction revealed that the proportion of nuclei containing more than 2n DNA was 2% in the control cells and 14.8% in the PHA-activated lymphocytes, with a difference between the groups of 12.8%. CFSE staining with subsequent incubation and assessment by flow cytofluorimetry demonstrated an increase in the percentage of proliferating cells from 1.68±0.9% in the control to 55.56±5.6% (p=0.00068) in the mitogen-stimulated sample.Conclusion: Modulation interference microscopy does not require the sample preparation and demonstrated comparable and even higher effectiveness compared to conventional methods for assessment of lymphocyte activity. At the same time, it allows for evaluation of the lymphocyte functional state in real time in the process of cultivation. This opens ample opportunities for evaluation immune cells for research and diagnostic purposes.

Structural and functional abnormalities of cell membranes in the end-stage chronic kidney disease

Background: Chronic kidney disease (CKD) is associated with abnormalities in all functions of the body systems including changes in intracellular processes. Assessment of erythrocyte electrophoretic mobility (EEM) in patients with CKD stage 5 on dialysis (5d) has becoming increasingly relevant, since this method characterizes the pathophysiological state of the patient and gives the possibility to modify treatment.Aim: To identify EEM characteristics in patients on programmed hemodialysis and their association with clinical and laboratory parameters.Materials and methods: We performed a cross-sectional observational study in 220 patients with confirmed CKD 5d. The average age of the patients was 56.5±1.4 years (26 to 85 years) and the duration of dialysis therapy was 3.7±0.4 years. The Kt/V urea adequacy index was 1.54±0.08. The control group included 60 healthy blood donors, comparable for their age and sex. EEM was assessed with Cyto-Expert kit (Axion Holding, Izhevsk, 2010) and the WT-Cell program (LLC Westtrade LTD, 2019). Statistical analysis was performed with BioStat 2019 software.Results: The patients on the programmed hemodialysis had lower values of oscillation amplitude (10.2±0.5 μm and 21.2±2.1 μm, p<0.001) and lower proportion of mobile red blood cells (69.5±1.8%, 89.7±9.9%, p<0.001), compared to the control group. Lower values of the oscillation amplitude were found in the age group of 25 to 44 years (9.0±1.0 μm, p<0.05). There was a weak positive correlation between age and amplitude of erythrocyte oscillation (R=0.20, p<0.05). There were differences in the oscillation amplitude values in the patients with various dialysis experience: 1 to 2 years, 11.3±0.8 μm, 2 to 5 years, 9.9±0.7 μm, 6 to 10 years, 9.4±1.3 μm, and over 11 years, 7.4±0.9 μm (p<0.05). The duration of dialysis therapy demonstrated a weak negative correlation with the amplitude of erythrocyte oscillation (R=-0.24, p<0.01). The erythrocyte oscillation amplitude was associated with systolic blood pressure before hemodialysis procedure (R=0.34, p<0.05) and with pulse pressure before hemodialysis (R=0.37, p<0.05). The proportion of mobile erythrocytes correlated with parathyroid hormone level (R=0.32, p<0.05).Conclusion: EEM in the patients receiving programmed hemodialysis have their specific characteristics related to a significant decrease in the oscillation amplitude proportional to the effective cell charge and lower proportions of mobile erythrocytes compared to those in the healthy control. The erythrocyte oscillation amplitude is negatively correlated with age and duration of dialysis therapy and is associated with blood pressure parameters and mineral bone indices.

Persistent Eustachian valve and transient arterial hypoxemia in a newborn: a clinical observation

The Eustachian valve (EV) is located in the orifice of inferior vena cava and belongs to structures of the normal heart. It plays an important role in the fetal blood flow by directing the flow of blood from inferior vena cava through an open foramen ovale to the left atrium, thereby ensuring the systemic flow in a fetus and bypassing the pulmonary circulation. After birth and upon closure of the foramen ovale, the valve ceases to function and tends to regress. Usually, a prominent EV is a clinically non-significant ultrasound finding. In isolated cases, however, it can cause significant hemodynamic abnormalities and subsequent rhythm disorders, delayed fetal development and transient hypoxemia in newborns. It can extremely rare be a cause of blood right-toleft shunting through the foramen ovale leading to desaturation. Clinically it can manifest by central cyanosis in newborns and infants. The differential diagnosis is made in neonatal intensive care units. We present a case of transient arterial hypoxemia in a newborn with prominent EV and inter-atrial shunt. A one-month old infant was transferred from the Department of Pediatric Cardiology with a history of transient hypoxemic spells related to right-to-left shunting via atrial septal defect caused by obstruction of the tricuspid valve by the prominent EV. The instrumental findings including contrast-enhanced tomography supported this hypothesis. The patient was stable for subsequent 10 days of the follow-up, which allowed for further conservative managements until the conventional time point for children with an atrial septal defect. Potential regress of the prominent EV, as well as natural growth of an infant and his/hers intracardiac structures, provide mostly favorable outcome without a surgical intervention. This was clearly illustrated in the clinical case.

Unbalanced atrioventricular septal defect with dominant right ventricle: diagnostic criteria, indications for biventricular correction, and results. A clinical observation series

Relevance: Surgical treatment for congenital heart disease (CHD) with borderline left ventricle (LV) dimensions is one of the most challenging issues in current pediatric cardiac surgery. Despite the prevailing general trend to the expansion of indications for biventricular repair of an unbalanced atrioventricular septal defect (AVSD) with a dominant right ventricle (RV), the diagnostic criteria for imbalance, feasibility of radical repair and its functional results are intensively discussed in the literature.Aim: To present quantitative criteria for the assessment of the LV size which could serve as an indication for biventricular repair of the right dominant unbalanced AVSD.Materials and methods: We present a series of 4 patients with AVSD and dominant RV, who underwent radical repair of the defect. The mean age of the patients was 2.4 years, and 3 of 4 had concomitant CHD: tetralogy of Fallot, double outlet right ventricle with pulmonary artery stenosis, and moderate hypoplasia of the aortic arch with subaortic stenosis. Three of 4 patients had previously undergone palliative interventions: two of them – pulmonary bending, one, the first stage of univentricular repair (atrioseptostomy, cavopulmonary anastomosis). Two children had been diagnosed with Down syndrome. The mean left ventricular end diastolic diameter (LVEDD) at baseline was 17.9 mm, corresponding to Z score of -5.4.Results: All four patients underwent biventricular repair of the defect with a two-patch technique. In one case, it was supplemented with placement of the pulmonary trunk homograft prosthesis, in the other with pulmonary valve commissurotomy and cavopulmonary anastomosis due to moderate tricuspid valve stenosis and in the third case the mitral valve was replaced. In 3 patients pacemaker implantation was performed. The criterion for feasibility of complete septation was the ratio of the longitudinal dimensions of the left and right ventricles (LAR > 0.7), confirmed by computed tomography performed before the surgery. The mean LVEDD after surgery was 28.3 mm, corresponding to Z score of -0.8. At the time of the hospital discharge, the left and right atrioventricular valves insufficiency did not exceed 2 and 1 degrees, respectively.Conclusion: Computed tomography allows for accurate measurement and comparison of the longitudinal dimensions of the heart ventricles with LAR index as a tool for assessment of the LV size before the biventricular repair. An additional prospective study is required to objectify the data obtained and identify predictors of an unfavorable outcome of radical repair in patients with right dominant unbalanced AVSD.

The choice of the insulin basal rate regimen at initiation of insulin pump therapy in routine clinical practice

Background: Numbers of patients with diabetes mellitus using insulin pumps have been increasing every year. Successful achievement of glycemic targets with continuous subcutaneous insulin infusion (CSII) is based on an adequate basal rate of infusion, carbohydrate coefficient and insulin sensitivity index. There are two approaches to basal insulin infusion rate, namely the flat one and the circadian; however, at present there is no convincing data on which one should be chosen at the start of insulin pump therapy.Aim: To compare two regimens of basal insulin infusion rate at initiation of insulin pump therapy in routine clinical practice.Materials and methods: We analyzed data from 120 patients with Type 1 diabetes mellitus, who were switched on insulin pump therapy in the Department of Endocrinology from 2017 to 2018. At initiation of CSII, 60 patients used the flat basal rate profile and the other 60 patients used the circadian basal rate, calculated with the Renner's scale. Safety of the two basal rate regimens was assessed based on glucose variability measured with continuous glucose monitoring during the first two days after the start of insulin pump therapy.Results: Mean (± SD) coefficients of variation in the groups with circadian and flat basal rate at Day 1 were 31.06±12.13 and 32.74±10.7, respectively (p=0.423); at Day 2, 26.78±11.27 and 28.83±10.7 (p=0.309). Median [Q1; Q3] areas under glucose curve (AUC) values above the glucose targets in the groups with circadian and flat basal rate at Day 1 were 0.37 [0.03; 0.89] and 0.48 [0.08; 1.75], respectively, at Day 2 0.44 [0.03; 1.57] and 0.31 [0.1; 1.5], respectively (p>0.05). Median glucose AUC values below the goal in groups with circadian basal rate and flat basal rate on the first day were 0.01 [0; 0.06] and 0.02 [0; 0.1], respectively (p=0.855), on the second day – 0.00 [0; 0.01] and 0.00 [0; 0.02], respectively (р=0.085). We also haven’t found any between-group differences in the prevalence of glucose deviations below and above the target, as well as in the time spent in normoglycaemia.Conclusion: The comparative analysis of two basal insulin rate regimens in Type 1 diabetic patients switched to insulin pump therapy has shown no significant differences between them. The use of Renner’s scale has no clinical advantages over the fixed basal insulin regimen at initiation of insulin pump therapy in adults.