[Questionnaire of the Ryzhikh National Medical Research Centre for Coloproctology is a new tool for assessing chronic pelvic pain and pelvic organ dysfunction]. / Oprosnik NMITs koloproktologii imeni A.N. Ryzhikh ­ novyi instrument otsenki khronicheskoi tazovoi boli i narusheniya funktsii tazovykh organov.

The article presents the work of a multidisciplinary team of experts from various fields of medicine to optimize the «Questionnaire for assessing chronic pelvic pain and pelvic organ dysfunction (QCPPD) of the Ryzhikh National Medical Research Centre for Coloproctology¼ for use in clinical practice. The survey of respondents was conducted from June 28 to September 28, 2021. As a result of this survey, by repeatedly making edits and clarifications during communication with respondents, the final version was obtained, which allows assessing the patient's subjective sensations by the nature and localization of pelvic pain, sensitivity disorders and pelvic organ function. The main objective of this Questionnaire is to differentiate patients with neurogenic pain from a huge number of patients with chronic pelvic pain. This aspect will allow a more targeted approach to the diagnosis and pathogenetically justified treatment of patients, including after appropriate instrumental examinations. The work of a multidisciplinary team implies a higher degree of objectification and terminological accuracy of the Questionnaire under discussion. The presented version of the «Questionnaire for assessing chronic pelvic pain and pelvic organ dysfunction (QCPPD) of the Ryzhikh National Medical Research Centre for Coloproctology¼ will be primarily used in coloproctological patients with pelvic pain problems and anal incontinence and obstructive defecation. Further studies will be directed to the clinical evaluation of the results of the work carried out.

[Reflux nephropathy in children: pathogenesis and prognosis. Part 2].

The second part of this review is devoted to the issues of modern and promising diagnosis of RN in children. The advantages and limits of the available methods for recording the structural and functional state of the kidneys in childhood are considered. Particular attention is paid to possibilities non-invasive methods for diagnosis and prediction of the disease course. Data on promising biomarkers of the early stages of RN formation and progression are presented. For the purpose of a comprehensive and adequate assessment of morphological changes in the kidneys, the necessity of studying various combinations of cytokines in biological media with the subsequent determination of the optimal spectrum is shown. The sensitivity and specificity of molecular indicators of renal damage reviewed as potential targets for renoprotective therapy in the nearest future.

[Reflux nephropathy in children: pathogenesis and prognosis. Part 1].

The purpose of this review is to analyze the modern literature about renal damage caused by vesicoureteral reflux (VUR). VUR is the most common urodynamic pathology in children and reflux nephropathy (RN), as its main complication, ranks first among the causes of chronic kidney disease (CKD). The risk factors for the appearance and progression of RN are presented in the first part of the review. In the framework of this issue, the main methods of treatment of VUR and associated urinary tract infection are described. The possibilities of conservative and surgical methods for the elimination of reflux for prevention of RN and prognosis of its course are considered. The main morphological aspects of RN formation are described.

Identification of Na+-Pumping Cytochrome Oxidase in the Membranes of Extremely Alkaliphilic Thioalkalivibrio Bacteria.

For the first time, the functioning of the oxygen reductase Na+-pump (Na+-pumping cytochrome c oxidase of the cbb3-type) was demonstrated by examining the respiratory chain of the extremely alkaliphilic bacterium Thioalkalivibrio versutus [Muntyan, M. S., et al. (2015) Cytochrome cbb3 of Thioalkalivibrio is a Na+-pumping cytochrome oxidase, Proc. Natl. Acad. Sci. USA, 112, 7695-7700], a product of the ccoNOQP operon. In this study, we detected and identified this enzyme using rabbit polyclonal antibody against the predicted C-terminal amino acid sequence of its catalytic subunit. We found that this cbb3-type oxidase is synthesized in bacterial cells, where it is located in the membranes. The 48-kDa oxidase subunit (CcoN) is catalytic, while subunits CcoO and CcoP with molecular masses of 29 and 34 kDa, respectively, are cytochromes c. The theoretical pI values of the CcoN, CcoO, and CcoP subunits were determined. It was shown that parts of the CcoO and CcoP subunits exposed to the aqueous phase on the cytoplasmic membrane P-side are enriched with negatively charged amino acid residues, in contrast to the parts of the integral subunit CcoN adjacent to the aqueous phase. Thus, the Na+-pumping cytochrome c oxidase of T. versutus, both in function and in structure, demonstrates adaptation to extremely alkaline conditions.

[Recommendations for the Protocol of functional examination of the anorectal zone and disorders classification: the International Anorectal Physiology Working Group consensus and Russian real-world practice].

This manuscript summarizes consensus reached by the International Anorectal Physiology Working Group (IAPWG) for the performance, terminology used, and interpretation of anorectal function testing including anorectal manometry (focused on high-resolution manometry), the rectal sensory test, and the balloon expulsion test. Based on these measurements, a classification system for disorders of anorectal function is proposed. Aim to provide information about methods of diagnosis and new classification of functional anorectal disorders to a wide range of specialists general practitioners, therapists, gastroenterologists, coloproctologists all who face the manifestations of these diseases in everyday practice and determine the diagnostic and therapeutic algorithm. Current paper provides agreed statements of IAPWG Consensus and comments (in italics) of Russian experts on real-world practice, mainly on methodology of examination. These comments in no way intended to detract from the provisions agreed by the international group of experts. We hope that these comments will help to improve the quality of examination based on the systematization of local experience with the use of the methods discussed and the results obtained. Key recommendations: the International Anorectal Physiology Working Group protocol for the performance of anorectal function testing recommends a standardized sequence of maneuvers to test rectoanal reflexes, anal tone and contractility, rectoanal coordination, and rectal sensation. Major findings not seen in healthy controls defined by the classification are as follows: rectoanal areflexia, anal hypotension and hypocontractility, rectal hyposensitivity, and hypersensitivity. Minor and inconclusive findings that can be present in health and require additional information prior to diagnosis include anal hypertension and dyssynergia.

[Predictors of perioperative complications in children with obstructive uropathy].

AIM: To identify predictors of perioperative complications in children with obstructive uropathy. MATERIALS AND METHODS: A total of 178 patients with obstructive uropathy were divided into 3 groups. In Group 1 there were 108 children with hydronephrosis, while Group 2 included 47 children with ureterohydronephrosis and Group 3 consisted of 23 children with bladder outlet obstruction according to the results of clinical, laboratory, microbiological, X-ray and pathologic study. The evaluation of the urine level of pro- (IL-8) and anti-inflammatory (IL-10) cytokines was performed at two timepoints, prior to treatment (1 point) and on the 3-5th day after the surgery (2 point) using "Vector - Best" (Russia, Novosibirsk) (IL-8), "Bender Medsystems" (Austria) (IL-10) on the enzyme immunoassay analyzer Stat Fax 2010 (USA). RESULTS: The active phase of chronic pyelonephritis was shown in Groups 1, 2 and 3 in 38%, 36% and 100% of cases, respectively. Microbiological examination of urine allowed to identify a causative agent in 85% and 89% of biopsy specimens from the ureteropelvic and ureterovesical junction, respectively. In all groups, Escherichia coli was a main pathogen (40%). In 25% of patients of Groups 1 and 2, isolated pathogens in biopsy specimen and urine were different. According to the evaluation of cytokines in the urine, during the active phase of chronic pyelonephritis there was an increase in the level of IL8 (p<0.0001) at points 1 and 2 in all patients. In the latent phase of inflammation, there was an increase in the concentration of IL-8 (p<0.04) and IL-10 (p<0.002) at point 2 in Groups 1 and 2. Using the ratio of IL-8 and IL-10, an index of inflammation activity (IIA) was suggested, whose values were increased in all Groups at point 1 and 2. Based on the regression analysis of the changes in IIA level, a model for predicting perioperative complications and an algorithm for personalized patient management were developed. CONCLUSION: Cytokines are indicators of latent inflammation in children with OU and may be predictors of perioperative complications.

[Role of clustered HER2/neu amplification as a marker for a special sensitivity to neoadjuvant anti-HER2 therapy with trastuzumab in patients with stage II-III breast cancer]. / Rol' klasternoi amplifikatsii gena HER2/neu kak markera 'osoboi' chuvstvitel'nosti k neoad''iuvantnoi anti-HER2-terapii trastuzumabom pri rake molochnoi zhelezy II­III stadii.

OBJECTIVE: To evaluate the influence of clinical and morphological factors and HER2 copy numbers on pathologic complete response (pCR) rates in patients with HER2-positive stage II-III breast cancer (BC). MATERIAL AND METHODS: Treatment results were studied in 73 patients with HER2-positive Stage II-III BC, who received treatment at the N.N. Blokhin National Medical Research Center of Oncology in 2015 to 2018. Treatment included neoadjuvant chemotherapy (NACT) with HER2-blockade and radical surgery followed by the evaluation of a pathologic response in the primary tumor and regional lymph nodes. The patients` age varied from 29 to 71; its median was 51.5; 45.2% of patients had primary operable stages (T1-3N0-1) and 54.8% had locally advanced tumors. All the patients had grade 2-3 anaplasia; luminal HER2-positive BC was diagnosed in 41.4% of patients; hormone-negative tumors were seen in 58.9%; 91.5% of patients had Ki-67 ≥20% in 75.3% of patients, preoperative systemic therapy included anthracycline-containing regimens (4AC + 4 x paclitaxel 175 mg/m2/12 × weekly administrations of paclitaxel 80 mg/m2; trastuzumab therapy was simultaneously performed with the administration of taxanes in the standard regimen) and anthracycline-free regimen TCH ± Pertuzumab regimen in 24.7% of cases. After NACT patients underwent surgery (radical mastectomy in 78.1%, breast-sparing treatment in 21.9%) with the assessment of morphological findings. Biopsy specimens obtained before the treatment was restudied; HER2 amplification was detected using a Dako HER2 IQFISH pharmDx kit according to its instruction and the 2018 ASCO/CAP guidelines. In 87.1% of cases, the HER2-positive status corresponded to the first category of the 2018 ASCO/CAP criteria for HER2-positive BC; clustered HER2 amplification was found in 30.1% of cases. The authors analyzed the frequency of bpCR and tpCR attainment by various clinical and morphological factors, as well as the impact of a HER2 amplification level on pCR rates. RESULTS: A breast pCR (bpCR) was achieved in 57.4% patients; bpCR and lymph node CR (lnCR) were noted in 48.9% patients. The rates of bpCR significantly depended on female age, chemotherapy regimen, addition of Pertuzumab, and HER2 copy number. That of bpCR in women less than 35 years of age, in those aged 36-50 years, and in those aged older than 50 years was 22.2, 57.7 and 71.9%, respectively (p=0.026). The maximum bpCR rate observed with the TCH±P regimen was 80.0%, that with anthracycline-containing regimes was 52.8% (p=0.045), and the addition of Pertuzumab increased complete response rates up to 88.9% (that with Trastuzumab was 54.2% (p=0.049). The relationship of bpCR rates to the detection of cluster amplification turned out to be highly significant (81% in its detection and 48.9% in its absence (p=0.013). In addition, clustered HER2 amplification was the only significant predictive factor for complete regression in the primary tumor and lymph nodes: in its presence, the tpCR rate reached 68.8% versus 38.7%. CONCLUSION: Clustered amplification of the HER2 gene is the most significant factor of sensitivity to anti-HER2 therapy for Stage II-III BC, and is associated with the maximum rate of both bpCR and total pCR. Further study of this factor may assist in optimizing the treatment algorithm for HER2 + BC.

[Prevention of perioperative complications in children with congenital uropathies].

AIM: To substantiate the expediency of immunomodulators and probiotics application pathogenetically in the comprehensive preoperative preparation in children with congenital uropathies (U). MATERIALS AND METHODS: The study includes 60 patients with various types of congenital uropathy (CU) (vesicoureteral reflux, hydronephrosis, obstructive ureterohydronephrosis), which were divided into 3 groups in accordance with the preoperative preparation complex. 1 group - 20 patients with VU, immunomodulating drug Kipferon was added to the therapy at the preoperative stage, group 2 - 20 patients with VU - with the addition of the biologically active additive (BAA) "Bifidum No791 BAG", 3 control group - 20 children with VU standard complex of preoperative preparation. The diagnosis of VU was established using a standard urological examination. The examination of the content of pro-(IL-8) and anti-inflammatory (IL-10) cytokines in the urine was performed before the start of treatment (1 point) and on the 3-5th day after surgery (2 point) for all patients using the method of enzyme-linked immunosorbent assay. RESULTS: Based on signs of systemic inflammation and urinary syndrome, initially patients of all groups (n=60) were in the latent phase of chronic obstructive pyelonephritis. After surgical correction pyelonephritis was diagnosed in all children at point 2, the most pronounced was in the control group. Manifestation of dysbiosis in the control group was more often by 20% than in group 2. The examination of the cytokine profile of urine showed an increasing the level of IL-8 (p<0.0001) at 2 points in all groups, the most significant was in the control group (p<0.002). An increasing the level of IL-10 (p<0.0001) was noted at point 2 in all groups, the most significant was in groups 1 and 2 (p<0.003). High values of the inflammation activity index were observed only at point 2 in the children of the control group (p<0.001). CONCLUSION: The using of immunomodulators and probiotics in the comprehensive preoperative preparation of children with obstructive uropathies reduces the risk, severity and duration of postoperative complications.

[Feminizing genitoplasty in virilization of the external genitalia].

The review focuses on the feminizing genitoplasty of the external genitalia in patients with disorders of sex development. The opinions of various surgeons and surgical schools on the timing, stages and methods of performing feminizing genitoplasty in girls with the virilization of the genitalia are presented. The development and improvement of surgical techniques for performing clitoroloplasty in patients with virilization of genitalia are described, as well as different types of labioplasty. The main methods of reconstruction of the urogenital sinus are given.

[Reflux nephropathy in children: early diagnosis and monitoring].

Vesicoureteral reflux (VUR) is the most common type of obstructive uropathy in children. Reflux nephropathy (RN) is one of the most common complications of VUR that inevitably leads to chronic kidney disease. Patients with end-stage kidney disease require costly treatment, and the only way to cure them is kidney transplantation. A timely institution of renoprotective therapy is a key factor helping to preserve the function of the native kidneys. Hence, it is necessary to devise new highly sensitive and minimally invasive methods for early diagnosis of RN. The purpose of this article is to review the molecular mechanisms of initiation and progression of kidney fibrosis and the opportunities of instrumental and non-instrumental methods for its diagnosis. Special attention is paid to highly specific and highly sensitive non-invasive methods for the detection of minimal changes in the renal parenchyma. The authors discuss the promising biomarkers for the diagnosis and prediction of RN.

[Modern approaches to diagnosis and treatment of tachyarrhythmia at military-medical organizations].

Modem approaches to diagnosis and treatment of tachyarrhythmia at military-medical organizations.. The article describes the principles of differential diagnosis and treatment of tachyarrhythmia. Developed algorithms of diagnostics and treatment of cardiac arrhythmias in the military-medical institutions. The algorithm relief hemodynamically stable rhythmic tachycardia. The results of interventional -treatment in 462 patients with tachyarrhythmia heart. The high efficacy and safety of radiofrequency ablation technique in patients with tachyarrhythmia heart.

[Hyposlenism After Splenectomy].

Splenectomy is a serious operation, which includes the removal of the largest peripheral immune organ. Vast array of different pools of immunocompetent cells and immune-factors eliminate from the body as a result of this operation. Occurrence of hyposplenism in our country pediatric service is not determined--there are neither clear criteria for its diagnosis, nor approved algorithms for prevention. Data of postsplenectomy sepsis incidence in Russia are unknown. In this review article authors give contemporary literature data relating to the issue of developing hyposplenism and changes in the body after removal of spleen. Systemic effect of organ-resecting operation and the basic directions of overwhelming postsplenectomy infection and sepsis prevention are discussed.

[Surgical treatment of rare combination of intestinal malrotation with secondary lymphangiectasia].

The rare combination of intestinal lymphangiectasia with malrotation of the duodenum in a child of three months of life is described. Basing on the literature review only 3 similar cases were described in the world practice. The boy with protein-losing enteropathy was examined at Moscow Scientific Centre of Children's Health. The child had vomiting, diarrhea, loss in body weight, hypoproteinemia, lymphopenia. The infectious nature of the disease was excluded. It had been suggested the Waldman desease (primary intestinal lymphangiectasia). The prognosis for such disease is unfavorable. An examination of the child was continued against the backdrop of ongoing symptomatic therapy. Complete physical examination included monitoring laboratory blood tests, X-ray examination with contrast, CT-scan, gastroduodenoscopy with biopsy of the mucosa of the small intestine. Malrotation duodenum with the recurrent mid-gut volvulus with the development of secondary intestinal lymphangiectasia was diagnosed. Modern methods of examination and multidisciplinary approach made it possible to diagnose the case. Operation to eliminate fixation duodenum resulted in the recovery of the patient. At the present time the child grows and develops according to age and does not require treatment. The prognosis for this disease is regarded as favorable.

[Kidney Injury in Newborns with Abdominal Compartment Syndrome].

The review represents the problems of a damage to the vital organs in newborns with the Abdominal Compartment Syndrome (ACS). Particular attention is paid to the key predisposing factors and key links of the renal damage's pathogenesis in newborns with ACS. This review presents the latest data about the role of the hypoxia at the initiation of damage of the renal parenchyma, the prospectsfor the use of various molecular markers for early diagnostics of nephropathy. Creation of molecular cell test system for the diagnostics and monitoring of renal damage in newborns with ACS is a promising trend in the treatment and prevention nephropathy in newborns.

[A new light on professional fitness expertise of patients with highly curable arrhythmia after hi-tech methods of treatment].

The peculiarities of a clinical course, results of pharmacological and interventional treatment in 447 patients with noncoronary cardiac arrhythmias were analyzed. A definition highly curable cardiac arrhythmia is introduced. The high efficiency and safety of the method of radiofrequency ablation in patients with highly curable cardiac arrhythmias that allows soldiers to leave the military service, as well as to enter military service under the contract. Proposed implementation of the control medical examination to conduct endocardial electrophysiological study and the subsequent medical examination to determine the category of fitness for military service not earlier than 6 months after surgery.

[Thyroid Adenomas in Children].

According to the papers thyroid nodules are quite rare in the first two decades of life. However, there are some exceptions, relating to areas with an iodine deficiency or affected by radioactive fallout, where the risk of nodules and carcinomas is increased. Therefore, it is a great challenge for the physician to distinguish between benign and malignant lesions preoperatively, and not only in these areas of greater risk. The authors analyzed current works, which are devoted to diagnostics and treatment of adenomas of thyroid gland in children. This literature review is based on works dedicated to epidemiology, histotypes study, and methods of diagnostics, surgical treatment, prognosis and complications of this pathology. The current tendencies in surgical approaches, intraoperative monitoring of recurrent laryngeal nerve are also discussed. The actuality of this problem is connected with last decade increase of adenomas in structure of thyroid gland nodules, increase of number of patients with multiple adenomas and with polypathias: adenomas with nodular goiter, autoimmune thyroiditis and cancer in children. The difficulties of diagnostic of adenomas are related to the similar clinical symptoms, cytogenetic characteristics of growth of benign and malignant lesions of thyroid gland. Additionally there is no systematic review about thyroid adenomas in children recent years.

[Confocal laser endomicroscopy of gastrointestinal tract: history, problems and perspectives in children].

In this review history, principles, technique and clinical applications of confocal laser endomicroscopy are briefly described. This technology allows to expand the diagnostic ability of traditional white light endoscopy and to assess effectiveness of therapeutic procedures in different gastrointestinal diseases. New experimental and clinical data in assessing small bowel barrier dysfunction as a predictor of relapse for inflammatory bowel disease is presented. Problems and perspectives regarding application of optical biopsy for gastrointestinal tract in pediatric practice are discussed.

[Radiofrequency ablation of focal atrial tachycardia from the right atrial appendage].

The authors report a case of elimination of permanently recurring focal atrial tachycardia affecting the right atrial appendage by radiofrequency catheter ablation in a 20 year old serviceman.

[Innovative methods of ventricular arrhythmia treatment].

The authors summarized the experience of the use of the stimulus and the activation mapping under fluoroscopic control to search for sources of ventricular ectopic followed by radio-frequency effects on the vulnerable zone arrhythmias. The authors presented an algorithm for finding a pathological focus on the basis of an evaluation of the surface electrocardiogram, followed by sequential endocardial mapping. The results of radiofrequency ablation of ventricular arrhythmia in different localization of the source are presented. The authors generalized and systematized the experience detection and cure of ventricular ectopy in 65 patients. The regularities of changes in the ventricular complex according to surface electrocardiogram in certain localizations of ectopic focus are revealed. Effectiveness of the operation of radiofrequency ablation with ventricular arrhythmias was about 90%, which is generally consistent with data from other clinics. Complications requiring additional interventions were not. Highlight the work areas of the endocardium, analysed the causes of inefficient operations and poor results. Alternative methods of destruction of the endocardium in complex localization of ectopic focus are suggested.

[Modern principles of diagnosis and prediction of course of chronic obstructive pyelonephritis in children].

An assessment of changes in the levels of cytokines, cell adhesion molecules, acute phase proteins in serum, urine and biopsy using ELISA was performed. The evaluation was performed in 167 patients with various congenital urinary tract obstructions in the perioperative period. It is shown that serum C-reactive protein and IL-6, IL-8 urine levels have high diagnostic significance for determining the severity of inflammation in the urinary tract in the development of chronic obstructive pyelonephritis at different levels of obstruction. The calculation of the proposed index of inflammation activity based on IL-8 and IL-10 urine levels in children in the dynamics allows to estimate the phase of inflammation and efficacy of the treatment.