Phenotypic and genotypic characterization of antibiotic resistance in military hospital-associated bacteria from war injuries in the Eastern Ukraine conflict between 2014 and 2020.

BACKGROUND: Infections from the recent conflict in Ukraine have been poorly investigated. AIM: To describe the phenotypic and genotypic mechanisms of antibiotic resistance in pathogens associated with war injuries in the Ukraine conflict. METHODS: This report describes a retrospective multi-centre microbiological survey conducted in four Ukrainian military hospitals between 2014 and 2020. The phenotypes of 813 organisms obtained from 1061 tests of 162 patients were analysed. Fifty-two isolates underwent whole-genome sequencing. FINDINGS: Resistance was highest in Acinetobacter baumannii, with 92.5% ((48/52) 95% confidence interval (CI) 81.8-97.9) resistant to fluoroquinolones, 83.0% ((43/52) 95% CI 70.2-91.9) resistant to aminoglycosides, and 67.9% ((37/52) 95% CI 53.7-80.1) resistant to carbapenems. In contrast, resistance to carbapenems was 55.6% ((30/52) 95% CI 41.4-69.1) in Pseudomonas aeruginosa, 42.9% in Escherichia coli ((12/28) 95% CI 24.5-62.8), and 32.8% in Klebsiella pneumoniae ((20/34) 95% CI 21.3-46.0). Multi-drug-resistant strains harboured an abundance of antibiotic resistance genes. K. pneumoniae co-produced class A and D ß-lactamases, in one case with blaNDM-1 and rmtC 16S rRNA methyltransferase. A. baumannii carried class A and D ß-lactamases but not metallo-ß-lactamases; in four isolates, carbapenemases were present with the RmtASE gene armA. P. aeruginosa harboured a wide range of class A and D ß-lactamases along with metallo-ß-lactamases, as well as the RmtB4 RmtASE gene. Gram-positive cocci were generally sensitive to the tested antibiotics. CONCLUSION: The incidence of resistance among the studied pathogens was higher than that in Ukrainian civilian hospitals and European countries. The discovery of P. aeruginosa, A. baumannii, and K. pneumoniae co-producing carbapenemases and RmtASEs is of particular importance, and hospitals should be vigilant for their emergence.

[; THE EFFECT OF COMPLEX REDUCING THERAPY WITH THE ADDITION OF A SYNBIOTIC ON THE DYNAMICS OF CLINICAL AND LABORATORY PARAMETERS IN PATIENTS WITH CHRONIC GOUTY ARTHRITIS].

The aim of the study was to assess the impact of complex urate-lowering therapy with the addition of a synbiotic on the level of cytokines in the blood and the quality of life of patients with chronic gouty arthritis.; The results of treatment of 68 patients (main group) and 62 patients (comparison group) with chronic gouty arthritis are presented. Patients of the main group took allopurinol at a dose of 300 mg per day with titration of the dose in the direction of increasing it by 100 mg once a month and additionally received a synbiotic 1 capsule three times a day. Patients in the comparison group received only allopurinol treatment. The duration of treatment was 3 months. The control group consisted of 25 practically healthy men of the corresponding age.; An addition of a synbiotic to the treatment regimen demonstrates an increase of urate-lowering effect of allopurinol (a decrease in the level of uricemia by 18.7% versus 13.3%, p <0.01), which was combined with a more pronounced anti-inflammatory effect: a decrease in the level of CRP by 75% against 26, 3% (p <0.01) and IL-1ß, IL-6, IL-8, IL-10 and TNFα (all p <0.001). According to the questionnaire on the SF-36 scale, in the main group in most subscales there was a statistically significant improvement in the dynamics of the indicators. According to the results of a survey according to the GSRS scale at the visit month 3, in the patients of the main group, the indicators of all subscales statistically significantly changed in the direction of improvement, except for the scale of gastroesophageal reflux syndrome.; The addition of a synbiotic to complex therapy for patients with gout allows morefaster achievement of target levels of uric acid in the blood, contributes to a more rapid normalization of blood CRP and the cytokine profile compared with allopurinol monotherapy. The tendency influence on the clinical manifestations of dysbiotic changes in patients with gout has an additional effect on the quality of life.

TELOMERE LENGTH, TELOMERASE ACTIVITY, HEART RATE VARIABILITY, OR OXIDATIVE STRESS: WHICH ONE IS MOST ASSOCIATED WITH THE ATHEROTHROMBOTIC STROKE IN THE ELDERLY?

The objective of this study - to evaluate the impact of the markers of oxidative stress and HRV to stroke. The comprehensive clinical and instrumental study involved 84 patients with the diagnosis "Cerebral Atherosclerosis" (CA). Study design: simple, prospective, non-randomized, with sequential inclusion of patients. All patients underwent generally accepted clinical, laboratory and instrumental examination. All patients received antihypertensive drugs and metformin if they had DM and didn't receive any statins. Patients were divided into the 2 groups: I - those who underwent ischemic stroke (IS), II - with CA of 1-2 degrees. Mean age was 65.5±10.2 and 66.0±9.3 years, respectively. The number of patients with type 2 diabetes and the average fasting glucose was comparable in both groups. The LF/HF indicator reflects the state of the sympatho-parasympathetic balance of the ANS. Large values of this indicator indicate the predominance of the tone of the sympathetic ANS, which was observed (p <0.05) in patients of the 2nd group, while HF, LF and VLF were also higher (p>0.05) in the group of patients with cerebral atherosclerosis of 1-2 stages and above normal international values. Both groups were comparable in terms of telomere length and telomerase activity, as well as markers of oxidative stress, with the exception of GSH, which was higher in post-stroke patients (p>0.05). Our findings show that markers of oxidative stress together with HRV indices are useful for the atherothrombotic stroke risk assessment in the elderly. Future longitudinal study with bigger sample size and, probably wide panel of markers required for clarifying links between oxidative stress, HRV and stroke.

THE EFFECTIVENESS OF MELATONIN IN THE COMPLEX TREATMENT OF HYPERTENSION IN PATIENTS WITH STAGE 5 CHRONIC KIDNEY DISEASE.

In recent years, there has been a progressive increase in the number of patients with chronic kidney disease (CKD), whose mortality risk is significantly higher than in general patients, which is associated with cardiovascular risks.In patients with CKD stage 5D before the start of replacement renal therapy for hypertension exceeds 90%. The aim -to analyze the efficacy and safety of the use of melatonin in the complex treatment of arterial hypertension (AH) in patients with CKD of 5 stage with impaired melatonin-forming function of the epiphysis (MFE). 60 people (35 women and 25 men) with a chronic kidney disease of 5 stage, which have violated MFE and AH were examined. For all patients in addition to antihypertensive therapy were prescribed the drug melatonin at a dose of 3 mg, which was taken once a day at 22:00 for 8 weeks. For all examined, before and after the course of treatment, were measured blood pressure (BP), Ambulatory Blood Pressure Monitoring (ABPM) and determination of the concentration of melatonin in the salivaby immunosorbent method. The examined patients showed a high frequency of MFE disturbance both in the daytime and at night - respectively, in 52,4% (p<0,001) and 82,6% (p<0,001). The dynamics of the diurnal BP on the background of treatment was due to changes in the degree of nocturnal decrease of BP, the number of patients in the main group with the "non-dipper" profile, decreased from 44,5% to 27,6% (p<0,05%), the proportion of patients with a daily profile of BP "night-peakear" from 22,4% to 4,8% (p<0,05%). Besides, a statistically significant of the number of persons with a daily profile of BP "dipper" increase in 30,2%. Against the background of complex treatment, there was a decrease in the patient's need for the dose and amount of antihypertensive drugs to achieve BP targets. Our data show a high incidence of MFE disorders in patients with CKD stage VD, and adding to the antihypertensive therapy of the drug melatonin in patients with CKD of 5 stage is effective and safe.

EFFICACY OF SPIRONOLACTONE IN ANTIHYPERTENSIVE THERAPY IN PATIENTS WITH RESISTANT HYPERTENSION IN COMBINATION WITH RHEUMATOID ARTHRITIS.

The aim of the study is to investigate the antihypertensive efficacy, structural and functional remodeling of the heart in patients with resistant hypertension (RH) and rheumatoid arthritis (RA) after 12-month of therapy. The treatment includes angiotensin-converting enzyme inhibitor, calcium channel blocker, diuretics, aldosterone receptor blocker (spironolactone), and immunosuppressive drug (methotrexate). 101 patients with hypertension (H) and RA were examined at the screening visit. 60 patients (mean age 61.9±9.1 years; 84.6% of women) meeting the criteria for RH were selected after 1 month. A randomized, controlled, parallel-group prospective study was conducted. Patients underwent general clinical, laboratory, and Doppler echocardiography investigations. They were divided into 2 groups: the main group, which represented patients whom to the basic antihypertensive therapy were added spironolactone 25 mg/day (group 1, n=30), and the comparison group, which represented patients who continued antihypertensive treatment without the addition of spironolactone (group 2, n=30) with 12- monthly observation. Groups of patients are comparable in age, sex, duration of RA and H, RA activity. The target blood pressure was achieved in 86.7% against 30.0% of patients (p <0.001) on spironolactone treatment compared to the inclusion of it. Therapy with spironolactone shown a probable decrease in the mean systolic blood pressure, diastolic blood pressure, and pulse blood pressure by 11.8%, 17.8%, and 5.4%, respectively. There was a reduction in the number of patients with left atrium dilatation from 86.7% to 63.3% (χ²=4.4, p=0.037) in group 1. The frequency of left ventricular hypertrophy (LVH) dropped by 10% (χ²=3.9, p=0.048) in patients of group 1. The incidence of eccentric LVH with left ventricular (LV) dilatation decreased by 2.2 times, concentric LVH with LV dilatation declined by 2.5 times after treatment in group 1. There was a further LV hypertensive remodeling in group 2: detection of concentric LVH without LV dilatation (χ²=3.3, p=0.04) was increased. There was a reduction of LV mass index (by 13.0%, p<0.01) due to a decrease in the stage of LV dilatation (by 7.3%, p<0.01), and the thickness of its walls (respectively interventricular septum and posterior wall by 17.3% and 15.2%, both p<0.01) in spironolactone group with the absence of probable changes in group 2. The LV contractile capacity, both regional fractional shortening and global ejection fraction improved (decline by 15.5% and 7.9% (both p<0.01)) in group 1 in the absence of dynamics in group 2. The incidence of LV diastolic dysfunction subsided from 83.3% to 40.0% (χ²=11.9, p<0.001) in patients of the spironolactone group, mainly due to a probable lessening in a number of patients with an abnormal LV relaxation from 60.0% to 36.7%. There was a lowering in E/e' med, E/e' lat and E/E' by 8.6%, 6.0% and 7.3%, respectively (all p <0.01) in patients on spironolactone therapy, which reflected the improvement of LV diastolic function. Patients of group 1 demonstrated a de-escalation of RA activity: a dropping of the DAS28-CRP from 5.6 (4.9-6.4) to 4.0 (3.4-5.0) (р<0,0001) in the absence of its dynamics in patients of group 2 (from 5.7 (5.0-6.1) to 5.6 (5.0-6.5) (p=0.6)). The addition of spironolactone to basic therapy demonstrates increased antihypertensive efficacy and potent antihypertrophic efficacy. These effects are combined with improved systolic and diastolic LV function and a decrease of clinical and laboratory activity of RA in elderly patients with RH in combination with RA.

[COMPARATIVE ESTIMATION OF THE SURGICAL TREATMENT RESULTS IN CYSTIC MENINGIOMAS OF THE BRAIN, USING THE STANDARD METHODS AND NEW TECHNOLOGIES].

The results of surgical treatment of 54 patients, suffering the brain cystic meningiomas of various localization, were analyzed. The patients were operated on in universal conditions by neurosurgeons of one operative team, of them 24 ­ using new technologies. Wide application of new technologies in surgery of the brain cystic meningiomas have permitted to reduce the surgical intervention invasiveness essentially, and, as a consequence, to reduce trustworthily the operation time essentially, as well as the intraoperative blood loss severity.

[Preoperative portal vein embolization: dynamics of portal pressure].

The pressure dynamics was studied in a portal vein (PV) in patients, suffering focal hepatic pathology, to whom portal vein embolization (PVE) was performed as a stage of preparation to radical hepatic resection. In 236 patients the immediate measurement of pressure in a PV was performed intraoperatively before and after PVE, in 26 - catheter for control portography and monitoring of pressure in a PV was left in its trunk for 24 h postoperatively. There was noted a pressure rising in a PV immediately after its embolization by 86.7%, positive correlation was established between PVE volume and pressure gradient in a PV before and after it. While doing monitoring during 24 h there was observed the pressure rising in a PV during 3 h after its embolization with subsequent lowering down to initial. Application of PVE as a preparation procedure for performance of extended hepatic resection, together with enhancement of residual liver minimizes sharp postresectional pressure rising in PV, what constitutes essential factor of the hepatocytes damage of residual hepatic part in immediate postoperative period.

[Modern possibilities of prophylaxis of intraoperative complications in organ salvage operations on the small pelvis organs].

Results of organpreserving operations on a small pelvis organs, performed in 337 patients-women, were analyzed. While heightened bleeding capacity of tissues in 39.3% women-patients when performing plastic operations on uterine tubes for ectopic pregnancy, cystectomy and conservative myomectomy with objective to stop hemorrhage the bleeding cessating plate Tachocomb was applied. It have permitted to perform organpreserving operations, to avoid complications, connected with intraoperative hemorrhage. Inclusion of Serrata preparation into rehabilitation therapy have promoted lowering of the pain syndrome severity and rate of occurrence of the adhesions process postoperatively.

[Prognostication of efficacy of simultant laparoscopic operations in accordance to the risk estimation scale, and the method of establishing of indications and contraindications].

Experience of surgical treatment was summarized and its results were analyzed in patients, suffering biliary calculous disease, coexistent with other surgical diseases of abdominal organs. Main aspects of diagnosis and prognosis for efficacy of simultant operations were presented, and there were also adduced the method of prognosis of the operative treatment results in such patients, the proposed principle of determination of indications and contraindications for performance of simultant laparoscopic operations, a scale of the risk estimation for performance of such operative interventions.

[Results of preoperative embolization of portal vein in patients with biliary hepatic tumors].

The results of preoperative embolization of portal vein (EPV) in 90 patients, operated on for biliary hepatic tumors, were analyzed. In 47 patients Klatskin tumor was revealed, in 29--peripheral cholangiocarcinoma, in 14--tumor of a gallbladder. In all the patients a radical major hepatic resection was planned, a checking hepatic volume (CHHV) did not exceed 40% of a noninvolved parenchyma. The EPV volume have corresponded generally to the planned resection volume. After performance of EPV a pressure in a portal vein have risen by 75%, and later it have had lowered step by step during 24 h. The CHHV index have raised from (354 +/- 72) up to (462 +/- 118) cm3, or from (33 +/- 7) up to (45 +/- 11)%, permitting to perform radical hepatic resection in 79 (87.8%) patients. Thus, application of EPV in patients, suffering biliary hepatic tumors, have permitted to increase the CHHV index after radical resection, and to raise resectability of such tumors.

[Experience of ASVS-test application in diagnosis of insulin-producing pancreatic tumor].

In 2009-2013 yrs in 7 patients, suffering insulin-producing pancreatic tumors, the ASVS-test was conducted, the result of which was compared with data of standard methods of investigation, including abdominal ultrasound, computer tomography and magnetic resonance imaging. The insuloma enucleation was performed in 3 patients, distal subtotal pancreatectomy with splenectomy--in 1 and the completed total pancreatectomy--in 1. The ASVS-test conduction is indicated in patients with diagnosed hyperinsulinism while impossibility to perform a topic diagnosis of insulinoma, in accordance to data of other noninvasive methods of diagnosis.

[Simultant laparoscopic operations for biliary calculi disease and hernia of the anterior abdominal wall].

The results of treatment of patients, in whom biliocalculous disease and hernia of anterior abdominal wall were diagnosed, were analyzed. The main aspects of diagnosis and prognosis of simultant operations in such patients, some technical procedures of operative interventions were depicted. Indications for performance of simultant completely laparoscopic and simultant laparoscopic combined operations in these patients were determined.

[Remote results of endoprosthesis of the infrarenal aorta aneurysm].

Endovascular endoprosthesis of infrarenal aorta aneurysm (EEIAA)--is miniinvasive highly technological method of treatment of a life-threatening disease. The rate of the endovascular interventions conduction for aortal aneurysm enhances every year in the world, the prosthesis construction and operative technique are upgrading constantly. The experience of the EEIAA endoprosthesis in 75 patients, aged 51-80 years old, 70 men and 5 women, was presented. The aneurysm size was from 4.3 to 8 cm. Preoperative examination of the patients have included the ultrasound scanning, computeric tomography (CT). Among existing complications there is haemorrhage from the access site more than 500 ml in volume, demanding the erythrocytic mass transfusion in 2 patients. The patients were followed up from 1 mo till 7 yrs. A hospital lethality was absent. Major cardiovascular accidents in the terms of observation up to 30 days postoperatively were absent. During the follow up period the mortality, connected immediately with the abdominal aorta aneurysm rupture, was absent.

[The role of transjugular hepatic biopsy in preparation of the patients for the large hepatic resection].

The results of transjugular hepatic biopsy (TJHB) were analyzed in 32 patients, in whom the performance of hepatic radical resection was planned for the focal hepatic diseases. The biopsy procedures have had succeeded in 100% of observations. The severe complications were absent. The specimen length have constituted 12 mm at average, fragmentation was noted in 32% of observations. All the specimen were recognized as affordable for histological studying. In 24 patients in terms of 2-4 weeks after biopsy the embolization of lobar branches of portal vein was performed with the objective to enhance the assumed residual hepatic volume. In all the patients in terms of 2-8 weeks the spacious radical hepatic resection was succeeded. The data obtained witness that application of TJHB is expedient in the patients, who are prepared for spacious radical hepatic resection, for estimation of the organ parenchyma state and prognostication of postoperative hepatic insufficiency.

[Diagnosis and treatment tactics for complicated pancreatic pseudocysts].

Experience of 84 patients treatment for complicated pancreatic gland pseudocysts is presented. Tactics of diagnosis and treatment for complicated pancreatic gland pseudocysts was elaborated and substantiated. Individualized treatment-diagnosis approach provides, first of all, the complications elimination, an adequate surgical treatment of pancreatic gland pseudocyst is possible in late period. For complicated pancreatic pseudocysts treatment miniinvasive methods were used predominantly, when their application is impossible or fails the open procedure is performed.

[A portal vein branch embolization as a method of preparation for liver resection].

The results of preoperative transcutaneous transhepatic embolization of portal vein (PTTEPV) were analyzed in 86 patients, suffering malignant hepatic tumors. Depending on a planned hepatic resection (HR) volume there was conducted embolization of a right lobar portal vein (in 45 patients), right vein with a vein of C(IV) segment (in 32), lobar portal vein with anterior right vein (in 9). In 3-4 weeks after PTTEPV there was noted the enhancement of ratio of a planned residual hepatic volume/total hepatic volume from 16.3 to 27.5%, permitting to perform HR successfully in these patients. In 4 (4.7%) patients HR was not performed because of progressing of the tumor development or a total thrombosis of portal vein. The data obtained witness, that PTTEPV constitute an effective method of the patients preparation for HR while presence of a planned small residual hepatic volume.

[Exceptionally high content of mRNA of IGF-II-associated protein in meningiomas].

A comparison of gene expression profiles in different types of human brain tumours and normal brain by Serial Analysis of Gene Expression (SAGE) revealed exceptionally high content of CTTGGGTTTT tag in meningioma and ependimoma SAGE-libraries. A search of the most relevant gene for this tag on the website "SAGE Anatomic Viewer" showed that it belonged to the nucleotide sequence of insulin-like growth factor II (IGF-II) gene as well as to the open reading frame 43 on a chromosome 11 (C11orf43). This nucleotide sequence encodes putative insulin-like growth factor II associated protein (IGF-IIA). mRNA for this protein is produced as a result of the processing of IGF-II gene primary transcript. Northern analysis of glial tumours and meningiomas showed the exceptionally high level of mRNA of IGF-II-associated protein in meningiomas. Protein, encoded by this mRNA, can play the important role in meningioma formation and may be used as their specific molecular marker.