Репозиторий Университета

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Purpose. Evaluation of the morbidity structure and demonstration CT-semiotics of the main diseases in patients with nontraumatic acute abdomen. Materials and methods. 905 studies of the abdomen performed in 2016 in the State Clinical Hospital named after S.P. Botkin in patients with acute abdomen. The studies were conducted natively, with contrasting per os, with intravenous enhancement, depending on the expected pathology. Results. The most common causes of acute abdomen were: acute intestinal obstruction (27%), pancreatitis (9%), urolithiasis and its complications (8%), oncology directly and its complications (7%), inflammatory changes in the gallbladder and diliary ducts (4%), inflammatory changes in the kidneys (3%). Also significant weight in the structure of morbidity was perforation of the bowel (2.5%), mesenteric thrombosis (2%), extraorganic inflammatory changes (2%). Only 5% of cases failed to reliably detect signs of a pathological process in the presence of a clinical picture. The main characteristics of the risk group for the emergence of acute abdominal pathology, such as the age of 32-67 years, the male sex, are revealed. A more detailed analysis of risk factors within the statistically most significant nosological groups was also carried out. The diagnostic efficiency index of multislice computed tomography (CT) for the above diseases varied from 95% to 97%, the sensitivity and specificity of the method depending on the disease were 95-97.8% and 93.2-97%, respectively, p> 0.05. Conclusions. CT allows to determine the nature of the disease quite accurately in emergency medical care in patients with nontraumatic urgent abdominal pathology. The identification of a risk group in the structure of acute nontraumatic abdominal pathology facilitates early diagnosis and timely treatment.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Introduction. Instrumental methods of examination may alter the course of treatment and patients' management. Several studies have shown that interobserver variability in values obtained with renal scintigraphy (RS) can be as high as 10%, however, RS remains the standard investigation for the assessment of split renal function. Objective. This paper aims to present how numerical analysis of abdominal MSCT results can be used to evaluate split renal function. Materials and methods. A prospective study was launched in a Research Institute for Uronephrology and Reproductive Health from November, 2015 to May, 2017. 88 patients were enrolled into the study (2 with hydronephrosis, 10 with hypertensive kidney disease, 5 with stone kidney disease, 2 with kidney anomalies, 69 with renal tumors). Comparison made between renal scintigraphy data and 3D MSCT-based models. Results. CT-based methods for the calculation of split renal function with 3D-models showed correlation with renal scintigraphy (p<0.004). Conclusion. A new approach for split kidney function assessment based on contrast-enhanced CT with 3D-models and mathematical analysis allows for both acquiring detailed data on clinical anatomy and evaluation of renal function to promote preoperative decision-making. It showed strong correlation with no significant difference in comparison with RS in terms of glomerular filtration rate, perfusion and plasma flow.

© 2018 Ima-Press Publishing House. All rights reserved. With the development of current neuroimaging techniques, their role in diagnosing epilepsy is becoming more significant and that is not only in identifying the disease that plays a key role in epileptogenesis, but also in assisting a clinician in the subsequent formulation of the diagnosis, in correcting drug therapy, and, in some cases, in addressing the issue of surgical treatment in the patient. The priority technique in this case is magnetic resonance imaging (MRI) that has high sensitivity and specificity in defining the location of minor and more major lesions of the brain structure and that includes a set of current sequences that can obtain important diagnostic information about the functional state of the brain. This article highlights the International League Against Epilepsy guidelines for MRI in patients with suspected epilepsy, assesses the use of and briefly characterizes both structural and functional pulse sequences that are most commonly included in the epileptological protocol. It considers major pathological processes and evaluates anatomical and functional changes in the brain structure, which play an important role in epileptogenesis.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Purpose. The purpose of this study is to compare the diagnostic performance of coronary computed tomographic angiography (CCTA) and stress test as a first-line examination for the diagnosis of stable coronary artery disease in outpatient settings. Materials and methods. The study prospectively enrolled 74 patients with typical and atypical angina symptoms lasting longer than three weeks, mean age-63,9±10,4 years, 28 (37,8%) women. Exclusion criteria: contraindications to iodine-containing contrast media, statins; GFR <45ml/min/1,73 sq m; inability to perform stress testing. All patients consistently underwent stress testing (standard Bruce protocol and The Modified Bruce protocol) and standard CCTA on a 640-slice CT scanner Toshiba Aquilion ONE. We determined pretest probability of CAD and stratified risks using SCORE and ACC/AHA scales. Statistical processing was performed with SPSS version 11,5 software. Results. Treadmill test results were positive in 51,4% of patients, among them according to CCTA: 19,15% had stenosis = 70%, 35,3% had stenosis 50-69%. CCTA revealed that 28,6% of males and 46,2% of females with typical and 66,7% of males and 50,0% of females with atypical angina symptoms with positive treadmill test had no evidence of atherosclerotic lesions. 4,05% of patients with negative stress testing had evidence of significant arterial lesions (stenosis >70%). According to the SCORE risk estimation, 67,6% of patients with atherosclerotic changes in coronary arteries had high risk, ACC/AHA score-70,6%. The sensitivity and specificity of the SCORE and ACC/AHA scales in revealing coronary atherosclerosis were 83% and 71%, 81% and 88%, respectively (p> 0.05). Conclusion. CCTA can be considered as a method for the primary diagnosis of stable coronary artery disease in outpatient practice.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Purpose. To demonstrate the effectiveness of volumetric multispiral computer tomography at the planning of focal liver masses treatment. To present visual 3D reconstructions of the liver, its vessels and focal masses. Material and methods. A group of patients included 25 patients with different focal liver masses. The age of the patients was from 29 to 83 years (mean age 62.1 years). Each patient had MSCT of abdomen with intravenous contrast injection. The following diagnoses were made according to the results of the examination, most of which were subsequently confirmed histologically: hemangioma-3 (12%), focal nodular hyperplasia-2 (8%), abscess-1 (4%), hepatocellular carcinoma-2 (8 %), cysts-4 (16%), metastases-13 (52%) cases. Results. Three-dimensional modeling allows effectively and without distortion to combine all the phases of contrasting in a single image, which gives complete information about the anatomical features affected by the pathological process of the liver. Conclusion. Processing DICOM images with the construction of 3D models of the liver helps the surgeon at the planning of surgical treatment, improves the spatial perception of the anatomical relationship of the organ, its vessels and pathological formations. However, three-dimensional modeling requires additional time and its clinical significance remains insufficiently studied.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. The analysis of 523 ultrasound examinations of the face in fetuses in pregnancy 10-14 weeks. Studies performed using 2D/3D/4D equipment transabdominal and transvaginal accesses and different modes (surface, multiplane and multislice). Investigated and presented to the rendering capabilities of individual facial structures at different age of gestation. Presents new and original methods for the visualization of the hard palate. The high informativeness of 3D/4D echography, means and tools, and its advantages in assessing the anatomy of the face in the first trimester of pregnancy are shown.

© 2018 Sankt Peterburg. All rights reserved. The purpose of this study was to assess the level of apoptosis in cells of human seminiferous tubules in normal and pathological spermatogenesis by revealing the proportion of immunostaining cells for caspase-9 and -3 and by comparing the expression of pro-apoptotic (BAK and BAX) and anti-apoptotic genes (BCL2 and BCLW). A retrospective study involved men (n = 42) who complained of childlessness in marriage for 2 years with a diagnosis of idiopathic infertility, established after physical, genetic, biochemical (hormones) and cytological (spermogram) analyzis. The biopsies of the testes as well as the autopsy material of men 22—35 (n = 10), 64—75 (n = 10) and 75—90 (n = 10) years were studied using the immunohistochemical method (caspase-9 and -3) and PCR-RT. The marking level for caspase-9 in spermatogonies with normal spermatogenesis is approximately at the same level (the proportion of stained spermatogonies is 39.5 0.33 % in young men, 35.6 0.44 % in the elderly, and 32.2 0.28 % in man of senile age), and increases when the maturation is blocked and in the case of focal variant of Sertoli-cell-only syndrome (64.3 0.39 and 72.0 0.41 %, respectively). When using antibodies to caspase-3, the percentage of immunopositive spermatogonia in normal spermatogenesis was 60.1 0.44 % in young men, 78.2 1.2 % in the elderly, and 87.3 0.9 % in men of senille age, and with idiopathic infertility, a sharp increase in the proportion of labeled spermatogonia was observed (an average of 91.4 1.1 %). In the case of hypospermatogenesis and the blocking of maturation, a significant increase in the relative level of expression of the proapoptotic genes of the internal pathway of apoptosis of BAX and BAK was observed against the background of a decrease in the expression of the anti-apoptotic genes BCL2 and BCLW, compared to men of the same age but with normal spermatogenesis. Based on the results, we can conclude that in the elderly’s testes the receptor-mediated pathway of apoptosis predominates over the mitochondrial (internal) pathway. In the idiopathic form of male infertility the internal pathway of apoptosis is dominant. An increase in the activity of apoptosis markers can be associated with impaired maturation of the germ cells in the meiosis block and with the depletion of the germ cell pool in Sertoli-cell-only syndrome.

It reports the results of primary basal blood flow in partially edentulous bone tissue with atrophy, as well as comparative evaluation of haemomicrocirculation level of the alveolar bone mucosa after bone augmentation via tunneling and conventional methods. The results of the initial state of microcirculation in the mucous membrane of the alveolar process in the partially edentulous area show a 45% decrease of blood flow (M), its intensity (s) by 60%. Microcirculatory shifts in blood flow levels indicators, its intensity, vasomotor activity are more evident when using the conventional method, where revascularization takes more than five months. When using the tunnel method, there is an improvement in haemodynamic mechanisms of tissue blood flow regulation. Microcirculation is restored 4 months after surgery.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Purpose. To present the possibility of the computed tomography (CT) in determination of a kidney injury for improving the quality of diagnostics and treatment of this group of patients. Materials and methods. Analyzed data comes from 72 T-researches with 50 patients with kidney injury at the closed injury of a stomach who were on treatment in Sklifosovsky Research and Clinical Institute for Emergency Medicine. Data of T was verified with the results of operations and autopsies. For determination of injury severity of a kidney the scale of Organ Injury Scale (OIS) was used. Results and discussion. Kidney injuries of the 1 degree (a contusion of a kidney and a subcapsular hematoma) were found in 12 patients, including the one with pre-existing pathology. Injuries of a kidney of the II degree were revealed in 14 patients: a cortical gap-in 9 cases, a subcapsular hematoma of a kidney with gap signs-in 3 cases; a subcapsular cyst with symptoms of hemorrhage and a gap-in two patients. Kidney injuries of the III degree were diagnosed in 7 patients in the form of a rupture of cortical substance from 12 mm to 18 mm deep. Damages of the IV degree were revealed in cases of 11 patients, including thrombosis of a segmentary branch of a renal artery in 6 patients. Injuries of a kidney of the V degree were revealed in 6 patients mainly in the form of fragmentation of a kidney. For an assessment of efficiency of treatment of 22 patients CT research in dynamics was executed, identification of complications served as the indication for repeated surgical intervention. Conclusions. T is an informative method which is possible to define not only an injury of a kidney, but also the degree of its severity. It allows to choose rational tactics for the treatment and to avoid an unreasonable nephrectomy. Performance of T in dynamics allows to estimate efficiency of treatment and in due time to diagnose complications.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Purpose. To improve the diagnosis of urolithiasis using the latest technique-dualenergy computed tomography (DECT). Materials and methods. A prospective study of a group of 91 (100%) patients was conducted at the department of radiology and urology at the Russian-Japanese Center in Sechenov University. All patients underwent a dual-energy CT scan to predict the chemical composition of urinary stones "in vivo". All patients underwent surgical treatment after diagnostics: distance lithotripsy (DLT), percutaneous nephrolithotripsy (PHNLT), contact ureterolithotripsy (CULT). All the stones after operations were subjected to physico-chemical analysis (X-ray phase analysis, infrared spectroscopy) in order to verify the composition. Further, the diagnostic value of the dual-energy computed tomography was assessed by comparing the DECT results with the physico-chemical analysis data. Results. Using DECT in the preoperative period, the following results were obtained: 40 patients had vevellit stones, 34 patients had Ca-containing stones without vevellit, 10 patients had stones with uric acid, in 7 patients stones were classified in the group of cystine/struvite. After verification studies in the postoperative period, the following urinary stone composition was determined: 42 stones-vevellit, 34 stones-Ca-containing stones without vevellit, 10 stones with uric acid, 5 stones-struvite stones. At the same time the following results were obtained incorrectly using DECT: 7 stones with vevellit from which 4 stones were postoperatively confermed to the group of Ca-containing stones without vevellit, 3 stones-struvite/cystine stones; 4 Ca-containing stones without vevellite were classified in the group of the vevellite; 2 struvite stones: 1 stone was incorrectly assigned to the group of uric acid, 1 stone-to the group of the vevellite; 1 stone uric acid was incorrectly assigned to the group of struvite stones. It should also be noted that 1 stone had a mixed composition (uric acid 70% + vevellit 23% + veddellite 7%), according to the results of DECT it was incorrectly assigned to the group of stones from uric acid, at the same time the prevailing component was determined correctly. Conclusions. In order to predict the chemical composition of the stone "in vivo" with a high degree of reliability DECT in the preoperative period can differentiate not only the urate and Ca-containing stones, but also separately identify the stones in which vevellit is the predominant component. The detailed differentiation of Ca-containing stones, as well as of more rare stones, such as struvite and cystine, requires further studies with more significant groups of stones.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Purpose. To identify the possibilities of computed tomography in detection of the nature and severity of the thoracic aorta trauma. Materials and method. Results of computed tomography (CT) of 15 patients from 2006 to 2017 with severe combined blunt injuries and thoracic aorta injury who had been treated in N. V. Sklifosovsky Research Institute for Emergency Medicine were analyzed. The majority of the patients were male 73% (n=11), the average age was 41,3+ 7,6 (22-79) years. The cause of injury in 12 cases were motor vehicle accidents, in 2 cases-falling from a height of more than three meters, in one case - A fall from patient's own height. Results. In evaluating the severity of the aortic injuries the classification proposed by the American Association of Thoracic Surgeons in 2013 was used. In our study there were no patients with Grade I; Grade II-small pseudoaneurysm (less than 50% of the circumference of the aorta) was identified in 8 patients; Grade III-big pseudoaneurysm (more than 50% of the circumference of the aorta) was identified in 3 patients; Grade IV-complete aortic rupture was identified in 4 patients. Simultaneously with the thoracic aortic injury pulmonary contusion was found in 9 patients, in 8-multiple fractured ribs, in 1-fracture of the sternum. In 8 patients mediastinal hematoma was identified, hemopericardium was found in 3 patients. Hemothorax was found in 12 patients. Signs of craniocerebral trauma were found in 6 patients, spinal cord injury-in 3 patients, injuries of the musculoskeletal system-in 4 patients, abdominal parenchymal organ injury was found in 4 patients (in 3 of these cases-of the liver, in 1-of the kidney), in one case sings of the duodenal rupture were found, in another-left-sided diaphragmatic rupture, in 1 patient with thoracic aortic rupture, a pseudoaneurysm of the hepatic artery was also found. Discussion. Using the classification of the severity of the aortic injuries by the CT results in patients with stable hemodynamics enables the ability to determine the degree of aortic stability, to predict the risk of rupture and to choose the type of optimal surgical intervention (early or delayed). There is a possibility to perform endoprosthetic repair of the aorta and surgical intervention of other areas against the background of controlled hypotension in patients with simultaneous traumatic aortic injury and other combined injuries. Conclusion. It is advisable to perform a CT examination at once of several anatomical regions when examining patients with severe combined injuries. Evaluation of the mediastinum structures in patients with severe combined injuries should be performed on the basis of a computed tomography of the chest with mandatory intravenous administration of contrast media. It is necessary to perform multiplanar and three-dimensional volume rendering to allow better visualization of the extent of thoracic aortic injuries. Choosing a method of treatment in victims with thoracic aorta injury is based on the use of endoprosthetics as an effective and low-traumatic intervention that can be used simultaneously with other surgical methods of treatment.

The radiation has an antitumor effect and causes radiation reactions and damage to surrounding tissues within the framework of combined antitumor treatment of patients with cancer of maxillofacial region. It also has an irreversible effect on the production of saliva by large and small salivary glands, and this must be taken into account when planning radiation therapy for this group of patients.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Purpose. Purpose of the study is to have a detailed examination and investigation of the patient with all the required parameters. Material and methods. Revision knee replacement prosthesis making a difference in treatment outcome. Results. The result after the sleeve operation was uneventful and the patient had no complaints or pain even after a year of surgery. Conclusion. Long term complications are comparatively less when a proper prosthesis is selected for the particular patient operation.

The study objective was to determinate variations of stato-dynamical functional markers of postural balance system in the process of malocclusion treatment. Twenty patients aged from 14 to 30 years with class II malocclusion were recruited for this prospective study. All patients underwent electromyography of mm. temporalis and mm. maseter in rest and at maximal jaws pressure. Postural balance was evaluated by stabilometry platform and body's regions relationship was assessed by computer optical topography. Orthodontic interventions included using occlusal splint, dental straps or 'TwinForce' device. There were two diagnostic sessions: before and after one month of orthodontic treatment. The majority of patients after anterior dislocation of mandible demonstrated significant increase in unilateral masticatory muscles activity (р<0.05) which correlated with iliac crest position. According to computerized topography data superior iliac crest position was registered in opposite side with regard to muscle hypertonia. According to stabilometry data forward translation of the mandible resulted in retroversion of total pressure point projection (р<0.05). Asymmetric muscle working in the process of occlusal adjustment may provoke postural imbalance in distal body regions. It dictates postural system condition monitoring during orthodontic treatment.

© 2018 Media Sphera Publishing Group. All rights reserved. The relevance of the investigation is due to the need to optimize the system for the primary prevention of drug addiction and use because of its insufficient efficiency in the Russian Federation. This problem is manifested in the low awareness of the population, primarily young people, about the negative consequences of the use of narcotic drugs and psychotropic substances and about the high associated risk of their involvement in the use of narcotics, including new types of psychotropic substances (synthetic narcotics). In this connection, the aim of our investigation was to develop a method for determining the potential efficiency of measures for the primary prevention of drug addiction and use, by applying mathematical modeling. The Kermak - McKendrick epidemic model of the susceptible infected removed (SIR) - like type was used as a basis to build a drug use spread model that represented as transition of groups of individuals from one state to another in relation to drug use. This gave rise to a simulation model estimating the magnitude of a drug use reduction in the risk group in relation to the initial one if varying effective preventive measures were implemented. The drug abuse scenario in case of effective measures was analyzed. Enhancing the effectiveness of measures for primary prevention of drug addiction was shown to lead to a stronger rather than linear decline in the size of a group at risk for drug and in the number of drug users. This model may be used to prepare programs, strategies for the primary prevention of drug addiction to evaluate their potential effectiveness.

© 2018 Pirogov Russian National Research Medical University. All rights reserved. The health of the cervical spine (CS) and the functional state of the pectoral girdle are interdependent. Injuries to the pectoral girdle can be an underlying cause of CS pain, including cervicalgia. The aim of this study was to evaluate the condition of the cervical spine in patients with cervicalgia developed after a pectoral girdle injury using radiographic and physical examinations. The study included 400 patients complaining of cervicalgia. Pain intensity was evaluated on the visual analog scale (VAS); the impact of the condition on patients' lives was assessed using the Neck Disability Index (Russian language). During physical examinations, the general health of the spine was evaluated and abnormalities in the cervical spine were noted. All participants underwent a radiographic scan of the cervical spine in the lateral and anterior-posterior projections; 49.5% of patients underwent postural digital radiography to evaluate their CS sagittal profile. All patients received an MRI scan. Based on the results, we identified certain functional changes in the cervical spine which possibly caused cervicalgia. Structurally and functionally, the changes were divided into static and dynamic. We conclude that cervical spinal pain is a common problem among patients with previous pectoral girdle injury.

© Bionika Media Ltd. Objective. To carry out a systems analysis of the data available in the current literature on the pathogenesis, therapy, and prevention of vaginal infections caused by the pathogens of bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). Material and methods. The review includes the data of foreign and Russian articles published in the past 10 years and found in Pubmed on this topic. Results. The paper highlights the main pathways of pathogenesis and the causes of recurrent vaginal coinfection. It describes methods for the treatment of women with BV and VVC and presents the optimal therapy and prevention schemes for recurrent vaginal infectious diseases, which have evidence-based effectiveness. Conclusion. The features of a microbial portrait and immune status predispose to recurrent BV and VVC, the presence of which results in coinfection. The cause of the latter is also repeated therapy for recurrent monoinfection. First-line therapy for BV is recognized to include metronidazole and clindamycin; the advantages of the latter are a wider spectrum of activity against the microorganisms that are difficult to identify. To treat coinfection and to prevent VVC in patients with BV, it is advisable to use fluconazole that also remains a first-line treatment option for vaginal infection caused by Candida albicans.

© 2018 Dynasty Publishing House. All rights reserved. The objective. To perform a budget impact analysis of a novel antiretroviral drug elsulfavirine (ESV) compared with currently used medical technologies. Materials and methods. The pharmacoeconomic model was based on the studies of efficacy and safety of two non-nucleoside reverse transcriptase inhibitors: ESV and rilpivirine (RPV) combined with standard basic tenofovir/ emtricitabine (TDF/FTC) therapy for 48 weeks. The studies were performed in similar clinical settings. The budget impact analysis assessed only direct medical costs of antiretroviral drugs within the chosen strategies of first-line antiretroviral therapy (ART). Results. It was shown that the treatment of ART-naive HIV patients with ESV is associated with 61,234.88 RUB less costs per patient in a 48-week course compared with RPV treatment. The analyzed values of cost effectiveness were lower for ESV strategy than for the strategy with the use of RPV. It makes ESV a more cost-efficient option within the developed model. Conclusion. The use of ESV is a preferable strategy of a first-line treatment of HIV. It is associated with less financial costs and more preferable cost effectiveness rate.

© Bionika Media Ltd. Objective. To determine a drug that is predominant in terms of pharmacoeconomic analysis for the treatment of infertility in patients with an insufficient ovarian response. Material and methods. An information search for publications on the appropriate topic of this study was conducted in the PubMed, Medlink, and Cochrane Library databases. A total of 134 articles and abstracts were found. Two publications on an open prospective randomized controlled trial by Ferraretti et al. (2004) and an open randomized trial by Carone et al. (2012) were selected for further analysis. These articles are unique in the contents and design of the study. Results. It was established that there was presently a limited number of studies available on the treatment of infertility in women with a suboptimal ovarian response, which had been conducted on a large sample of patients. An economic evaluation of the effectiveness of infertility treatment was made in patients with an insufficient ovarian response on the basis of effectiveness analysis, cost analysis, cost-effectiveness analysis, budget impact analysis, and sensitivity analysis. The compared alternatives were follitropin-alpha + lutropinñ alpha/ recombinant follicle-stimulating hormone (rFSH) + recombinant luteinizing hormone (rLH), follitropin-alpha/ rFSH, and menotropin/human menopausal gonadotropin (hMG). Conclusion. The results of pharmacoeconomic analysis have shown that follitropin-alpha + lutropin-alpha dominates in terms of cost-effectiveness analysis and leads to cost savings in the treatment of infertility in patients with a suboptimal ovarian response.

AIM: To develop predictive model for hepatic insufficiency in obstructive jaundice.MATERIAL AND METHODS: Obstructive jaundice was modeled by the author's method on 48 mini pigs, while morpho-functional features of erythrocytes were studied by using of INTEGRA Aura atomic force microscope (NT-MDT, Zelenograd, Russia). Histological specimens were stained with hematoxylin and eosin. Discriminant analysis was used to create predictive model for hepatic insufficiency.RESULTS: Mathematical model of hepatic insufficiency prediction has been developed. Sensitivity and specificity of this model were 94.1% and 74.2% respectively. Total percentage of correct predictions was 81.3%.CONCLUSION: Severe obstructive jaundice contributes erythrocyte's transformation from biconcave to dome-shaped followed by changes of its physical properties. Erythrocyte's volume and activity of cytolysis enzymes are the most informative to predict hepatic insufficiency. Our model allows us to diagnose this complication at early stages and to correct pre-, intra- and postoperative therapy.