Subgroup 1B Research Articles

Preventing false discovery of heterogeneous treatment effect subgroups in randomized trials

BackgroundHeterogeneous treatment effects (HTEs), or systematic differences in treatment effectiveness among participants with different observable features, may be important when applying trial results to clinical practice. Current methods suffer from a potential for false detection of HTEs due to imbalances in covariates between candidate subgroups.MethodsWe introduce a new method, matching plus classification and regression trees (mCART), that yields balance in covariates in identified HTE subgroups. We compared mCART to a classical method (logistic regression [LR] with backwards covariate selection using the Akaike information criterion ) and two machine-learning approaches increasingly applied to HTE detection (random forest [RF] and gradient RF) in simulations with a binary outcome with known HTE subgroups. We considered an N = 200 phase II oncology trial where there were either no HTEs (1A) or two HTE subgroups (1B) and an N = 6000 phase III cardiovascular disease trial where there were either no HTEs (2A) or four HTE subgroups (2B). Additionally, we considered an N = 6000 phase III cardiovascular disease trial where there was no average treatment effect but there were four HTE subgroups (2C).ResultsIn simulations 1A and 2A (no HTEs), mCART did not identify any HTE subgroups, whereas LR found 2 and 448, RF 5 and 2, and gradient RF 5 and 24, respectively (all false positives). In simulation 1B, mCART failed to identify the two true HTE subgroups whereas LR found 4, RF 6, and gradient RF 10 (half or more of which were false positives). In simulations 2B and 2C, mCART captured the four true HTE subgroups, whereas the other methods found only false positives.All HTE subgroups identified by mCART had acceptable treated vs. control covariate balance with absolute standardized differences less than 0.2, whereas the absolute standardized differences for the other methods typically exceeded 0.2. The imbalance in covariates in identified subgroups for LR, RF, and gradient RF indicates the false HTE detection may have been due to confounding.ConclusionsCovariate imbalances may be producing false positives in subgroup analyses. mCART could be a useful tool to help prevent the false discovery of HTE subgroups in secondary analyses of randomized trial data.

Reduced longitudinal cardiac strain in asthma patients

ABSTRACTObjective: There is limited knowledge about the potential relationship between asthma and heart function. Aim of our present study was to examine if asthma may be associated with manifest or subclinical heart dysfunction. Methods: Seventy-two allergic mild-to-moderate and severe asthma patients and 20 matched controls were enrolled in the study. Depending on the anti-asthmatic therapy, four subgroups of asthma patients were created: patients under long-acting beta2-agonists (LABA) and inhaled cortisone without oral cortisone treatment with (1a) versus without (1b) additional omalizumab therapy; patients with LABA, inhaled cortisone and omalizumab treatment with (2a) versus without (2b) oral cortisone. Standard echocardiographic parameters as well as global longitudinal left and right ventricular strains as determined by ultrasound-based speckle-tracking method were evaluated. Furthermore, NT-pro-brain natriuretic peptide (NT-pro-BNP), immunoglobulin E (IgE), C-reactive protein (CRP), and blood count were assessed in asthma and control groups. Results: There were no relevant differences in standard echocardiographic measures between both asthma groups and the control collective. Longitudinal left ventricular strain values were reduced significantly in severe and mild-to-moderate asthma groups (−12.91 ± 0.84% and −13.92 ± 1.55%, respectively), whereas longitudinal right ventricular strain values were additionally relevantly decreased in severe asthma (−10.35 ± 1.04%) compared to the control (−16.55 ± 0.49% and −18.48 ± 1.90%, respectively). Cardiac strains were similar in subgroups 1a and 1b. In contrast, patients from subgroup 2a presented reduced heart strains and decreased lung function compared to those from 2b. CRP, IgE, and eosinophils were significantly increased in asthma versus control individuals. Conclusions: Allergic asthma, especially severe asthma is associated with subclinical impaired left and right ventricular function as determined by speckle-tracking analysis.

Evaluating the Ability of the New Subclassification to Prognosticate Outcomes Following Hepatectomy for Patients with HBV-Related HCC.

Recently, experts proposed subclassification for BCLC B patients. In this study, we aimed to evaluate the efficient of subclassification of patients with hepatitis B virus-related hepatocellular carcinoma (HCC) in Barcelona Clinic Liver Cancer (BCLC) staging system. Seven hundred twenty-nine consecutive hepatitis B virus-related HCC patients with BCLC stage B classification who underwent hepatectomy in the period 2006-2012 were retrospectively analyzed. Patients were reclassified based on the new proposed subclassification of the BCLC B stage from B1 to B4. The prognosis of subclassification was tested using Kaplan-Meier statistics analysis. There were 145 (19.9%), 480 (65.8%), 62 (8.5%), and 42 (5.8%) patients in B1, B2, B3, and B4, respectively. The result suggested that overall and tumor-free survival rates among the B1, B2, and B3 subclassification in the Bolondi system had significant difference (P < 0.05). However, no significant difference was found between B3 and B4 subclassifications. Cox regression showed that BCLC B subclassification, largest/smallest diameter, and anatomic liver resection were independent predictors of tumor-free survival. BCLC B subclassification and anatomic liver resection were independent predictors of overall survival. The subclassification of BCLC stage B can be used in patients with HBV-related HCC who underwent curative intent hepatectomy. Patients in BCLC B1 and B2 subgroups should be treated more aggressively than patients in B3 and B4 subgroups. B3 and B4 groups should be merged for patients with HBV-related HCC who underwent curative intent hepatectomy.

Abstract PD7-12: Molecular subtyping of male breast cancer by the International male breast cancer program (IMBC): EORTC 10085/TBCRC 0-29/BIG 2-07/NABCG/BOOG 2009-04

Abstract Introduction. Male breast cancer (male BC) is a rare disease for which disease management is extrapolated from females. IMBC, an international consortium, which previously reported on clinico-pathological aspects, now reports on molecular subgroups revealed by RNA sequencing and their relation to patient outcome. Methods. Tumor samples from the retrospective MALE BC registry diagnosed between 1990-2010 and with pathology and outcome data (relapse-free- (RFS) and overall survival (OS)) were included (n=699). To allow the discovery of prognostic features, we selected, stratified for known risk factors (TN stage, grade, age at diagnose and adjuvant endocrine treatment), from the cohort 152 cases with poor (RFS &amp;lt;= 4 yrs) and good outcome (RFS &amp;gt; 7yrs) evenly distributed. Here, we report RNA sequencing results of the first 73 cases, 38 with poor and 35 with good outcome. RNA sequencing reads were used to generate gene expression values and to report transcripts carrying driver mutations. Unsupervised clustering identified subgroups and within subgroups differentially expressed genes were identified. The reported prognostic male BC subgroups M1 and M2 (Johansson BCR 2012(14):R31) were also annotated. All identified subgroups were related to outcome using logistic regression (p-value using Wald test). Results. Unsupervised clustering revealed 2 main subgroups of which group 1 was enriched for expression of ER target genes, WNT3 and genes from amplicons known for female BC, e.g. 19p13 (CCNE1), 8q24 (MYC), and 11q13 (CCND1). The biology of the smaller group 2 was less defined but TGFβ2 expression was high as were various kallikreins (KLK) including interestingly KLK3 (prostate specific antigen). Other known amplified regions [(8p11 (FGFR1), 20q13 (ZNF217) and 12q15 (MDM2)] and mutated transcripts [PIK3CA (H1047R/L/Q; E542K, E545K, N345K; 16% of cases), TP53 and SF3B1 (K700E) (2% of cases)] were identified. Profound tumor infiltrate gene expression was present in 5% of cases and one third of cases expressed proliferation markers. Except for TP53, none of these latter characteristics were unevenly distributed among the 2 main subgroups. ER and AR were highly correlated, particularly in group 1. The two main groups could be further subdivided. Group 1 comprised 3 subgroups of which subgroup 1a expressed TFF1/3 and NAT1, well-known ER targets, while subgroups 1b and 1c expressed other ER targets,respectively BEX1 and PITX1. HOXC cluster expression differentiated subgroup 1b from 1a and 1c. None of these intrinsic subgroups were, however, related to RFS. The previously reported M2 subgroup, which largely segregated with subclusters 1a and 1b, was associated with a better RFS than the M1 subgroup (OR=2.9; 95%CI 1.1-7.5; p-value=0.03). Conclusions. 1) Intrinsic subtypes of male BC were revealed and their subgrouping is defined by ER associated subsets of genes. 2) The association of the reported M2 subgroup of male BC with longer RFS was validated; 3) Currently identified biological characteristics of male BC may improve future treatments. The full report on 152 cases including a comparison to female BC will be presented at the conference. This research was funded by Breast Cancer Research Foundation Citation Format: Martens JWM, Sieuwerts A, Ponchet C, Smid M, de Weerd V, Slaets L, Piper T, van Deurzen CHM, Schroder CP, Stangle C, Kloosterman W, van Leeuwen-Stok E, Nilsson C, Vermeij J, Peeters S, Goulioti T, Nowaczyk M, Aebi S, Rubio IT, Kelly C, Bayani J, Porter P, Murray M, Hudis C, Middleton L, Korde L, Ruddy K, Winer E, Bogler O, van den Weyngaert D, dal Lago L, Fraser J, Benstead K, van Asperen C, Linderholm B, Hedenfalk I, Tryfonidis K, Giordano S, Bartlett J, Cardoso F. Molecular subtyping of male breast cancer by the International male breast cancer program (IMBC): EORTC 10085/TBCRC 0-29/BIG 2-07/NABCG/BOOG 2009-04 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD7-12.

ERF transcription factors involved in salt response in tomato

ERF transcription factors are important regulatory components of ethylene signaling, known to be involved in plant development and stress responses by regulating the expression of ethylene responsive genes. However, relatively less is known about the function of ERF gene family in wild tomato response to salt stress. Previously, we have carried out a microarray analysis on the salt-responsive genes in salt tolerant wild tomato Solanum pimpinellifolium ‘PI365967’. Five ERF genes (SpERFs) with induced expression upon salt treatment were subsequently selected for further characterization. Sequence analysis revealed that the seven amino acid residues in ERF proteins which are critical for their binding to the GCC-box in the promoter of ethylene responsive genes were conserved in five SpERFs. Two of five SpERFs (SpERF.B7 and SpERF.C11) belong to B3 sub-group as predicted by phylogenetic analysis. Expression analysis indicated that two SpERFs of B3 sub-group were more strongly induced in salt-tolerant genotypes than in salt-sensitive genotypes, in the order of PI365967 > LA2711 > Moneymaker, suggesting a positive role of B3 sub-group SpERFs in salt stress in tomato. To further confirm the function of B3 SpERFs in salt response, SpERF.B7 (one of two B3 SpERFs) was over-expressed in Arabidopsis. Consistent with our expectation, transgenic lines exhibited enhanced salt tolerance. These results will provide useful information for improving salt tolerance in tomato breeding in the future.

Особливості ліпідного обміну в жінок із гострим коронарним синдромом без підйому сегмента ST залежно від гормонального статусу

Introduction. The role of lipid metabolism disorders in the process of atherogenesis has long been established. It is known little about the effects of dyslipidemia on the development of coronary artery disease in women. There is a perception that the effect of endogenous estrogens during the fertile period of woman's life slows down the manifestation of atherosclerosis in women and before the onset of menopause, the incidence of CVD in women is lower. Hypercholesterolemia or atherogenic dyslipidemia is a particular danger in the development of CVD in women and the risk of macrovascular injury associated with it is due to the long asymptomatic course and significant prevalence in the female population.The aim of the study – toconduct a comparative analysis of lipid metabolism in women with acute coronary syndrome without ST segment elevation(STEMI) and practically healthy women, depending on the hormonal status.Materials and Methods. We examined 157 women aged 35–72 years (average age 56.54±0.87 years). Among them, 112 female patients with STEMI (group 1) aged 39 to 72 years (average age 58.52±0.99 years). The comparison group (group 2) were 45 practically healthy women aged 35 to 71 years (average age 52.58±1.58 years). The levels of female sex hormones were determined. The lipid metabolism indices in women were measured.Depending on the type of hormonal status, women of the 1 and 2 groups were divided into subgroups A and B consisted of 64 patients with STEMI, aged from 39–72 (middle age – 60.77±1.16), 2А – 26 practically healthy women 42–71 years (average age 58.64 ± 2.18 years) with hormonal signs of postmenopause: estradiol level &lt;80 pmol/l (21.79 pg/ml) and LH/FSH &lt;1 ratio index. The subgroup 1Bincluded 48 female patients with non STEMI at the age of 35 to 65 years (mean age 52.29±1.63), IIB-19 practically healthy individuals of the female population aged 35 to 58 years (middle age – 49.84±1.84years) with estradiol levels&gt; 80 pmol/l (21.79 pg/ml) and a ratio of LH/FSH&gt; 1.Resultsand Discussion. Almost all female patients of the IA subgroup had a level of total cholesterol level more than 4 mmol/l, which was 1.3 times significantly greater than that of IB subgroup (95.31±2.64% (IA) vs 75.00±6.25 % (IB)). The mean level of LDL cholesterol is significantly higher in women IA subgroups (4.50±0.21 mmol/l (IA) vs 3.44±0.24 mmol/l (IB)). In 73,43±5,52% of the IA subgroup, hypertriglyceridemia was detected, which was 1.6 times more likely to be registered (45.83±8.19%) than in patients with IB subgroups. The proportion of patients with lowered LDL cholesterol was almost 1.5 times lower in the IA subgroup (37.50±6.05% (IA) vs 52.08±7.21% (IB)). The mean HDL cholesterol level in the IB was significantly lower in comparison with the subgroup 1A (1.04±0.03 mmol/l (1B) versus 1.16±0.05 mmol/l (IA). Diabet (31.25±5.15 %), smoking (54.16±7.19 %) and occupationally hazardous labor (89.58±4.41 %) was significantly higher in patients of the subgroup 1B.Conclusions.In women with STEMI, regardless of the hormonal balance of female sex hormones, there is a greater prevalence and severity of dyslipidemia compared with healthy individuals. Estrogen deficiency in postmenopausal women with STEMI cause severe lipid and lipid metabolism disorders, which contributes to the development of acute coronary syndrome. Lower levels of HDL cholesterol in patients with estrogen retained estrogen compared to estrogen-deficient patients are due to higher prevalence of diabetes (31.25±5.15 %), smoking (54.16±7.19 %) and occupationally harmful work (89.58±4.41 %), along with the presence of traditional risk factors of STEMI in these women.

Эффективность хронофармакотерапии у пациентов с хронической сердечной недостаточностью с сохраненной фракцией выброса и различной чувствительностью к соли

Included 130 patients with uncontrolled AH, type 2 diabetes and HFpEF (81 women and 49 men), median age - 59 (38-72) years. Patients were divided into 2 groups: saltsensitive (group 1) and salt-resistant (group 2), and then randomized to 2 subgroups depending on the treatment option: morning ramipril and indapamide retard, in the evening amlodipine (subgroup 1A and 2A) or in the evening ramipril, in the morning indapamide-retard and amlodipine (subgroup 1B and 2B). Initially and after 24 weeks of antihypertensive therapy, an echocardiographic study was carried out with an assessment of the main indicators of the structural and functional state of the left ventricular (LV) myocardium, a 6-minute walk test for determining the functional state of patients. After 24 weeks in all subgroups there was a reliable positive dynamics of echocardiographic indicators. In the group of salt-sensitive patients, the reception of the angiotensin converting enzyme inhibitor (ACE inhibitor) in the evening and thiazide diuretic (TD) + calcium antagonists (AC) in the morning provided a signifcantly more signifcant reduction in the majority of LV myocardial remodeling parameters compared with the administration of ACE inhibitor + TD in the morning and AK in the evening. In the case of salt-resistant patients, comparable positive changes in echocardiographic indicators were noted against the background of both dosing regimens during the day. Against the background of the treatment, irrespective of the salt sensitivity and dosing regimen, an unreliable and comparable increase in the distance of the 6-minute walk test was recorded during the day. In salt-sensitive patients with AH, type 2 diabetes and HFpEF, the use of ACE inhibitor before bedtime provided signifcantly more signifcant regression of the parameters of the structural and functional state of LV myocardium compared with the morning reception. In the group of salt-resistant patients, the efcacy of both dosing regimens during the day was comparable.

Monitoring of sexual satisfaction couples after penile implantation

The objective: analysis of the effectiveness of implantation of the prosthesis of the penis in the treatment of erectile dysfunction (ED) with an emphasis on the satisfaction of both sex partners. Materials and methods. The study involved 80 couples (men were diagnosed with ED of severe degree of organic form), later men underwent penile implantation. Patients were divided into two groups: 1st group - 40 pairs, in which the male was implanted with a plastic implant; 2nd group - 40 pairs, in which the male was fitted with a hydraulic implant. To diagnose the organic form of ED, dopplerography of the penis vessels, a test with local negative pressure, dynamic cavernosography, angiography was used.Results. After the surgical intervention, 5.0% of the patients of the 1st group and 12.5% of the 2-nd group had minor complications that did not require replacement of the implant. Sexual life was resumed no earlier than 6 weeks later. As a result of the study, it was found that the frequency of sexual acts in subgroups 1a and 2a averaged 10 ± 2.2 times a month, in subgroups 1b and 2b – only 4 ± 1.2 times a month.Сonclusion. Psychological counseling increases the possibility of interpersonal adaptation of sexual partners after penile implantation from 65% to 95%.

ЛИПИДСИНТЕЗИРУЮЩАЯ ФУНКЦИЯ ПЕЧЕНИ У БЕРЕМЕННЫХ С ЦИТОМЕГАЛОВИРУСНОЙ ИНФЕКЦИЕЙ

Lipid synthesis function of the liver was studied by the contents of total cholesterol, lipoproteins of high density, lipoproteins of low density and triglycerides in 270 women in the second trimester of pregnancy. The first group (control) included 30 women with a physiological course of pregnancy. The main group consisted of the patients of the second, third, fourth and fifth groups with chronic cytomegalovirus infection (CMVI). Each of them were divided into two subgroups: subgroup A included the women with progressing pregnancy which terminated with the delivery in term; subgroup B - the patients with miscarriage threat whose treatment led to prolongation of the pregnancy and delivery at the 38-40th weeks of gestation. The second group included 60 women with latent chronic CMVI. The third group included patients with reactivation of chronic CMVI (antibody titers of IgM to CMV were 1:200-1:400, antibody titers of IgG to CMV were 1:200-1:400, avidity index of IgG antibodies was more than 65%). The fourth group included 60 patients with acute phase of chronic CMVI (antibody titers of IgM to CMV were 1:200-1:400, antibody titers of IgG to CMV were 1:200-1:800, avidity index of IgG to CMV was more than 65%), the fifth group had 60 patients with reactivation of chronic CMVI (antibody titers of IgM to CMV were 1:200-1:400, antibody titers of IgG to CMV were 1:400-1:1600, avidity index of IgG antibodies was more than 65%). When comparing the parameters of the first group with such-like ones of 2A and 2B subgroups there were not found any changes in the contents of total cholesterol, lipoproteins of high density and lipoproteins of low density and triglycerides; whereas in 3A subgroup there were revealed lower values of lipoproteins of low density (3.55±0.09 mmole/L; p&lt;0.01), and in subgroup 3B there was a decrease of concentration of total cholesterol till 6.33±0.14 mmole/L (in control it was 6.7±0.09 mmole/L; p&lt;0.05) and lipoproteins of low density till 3.43±0.10 mmole/L (in control it was 3.93±0.09 mmole/L; p&lt;0.001). In the patients of subgroup 4B in comparison with the first group there were registered lower values of total cholesterol (6.20±0.15 mmole/L; p&lt;0.01) and there was a growth of lipoproteins of high density till 2.04±0.13 mmole/L (p&lt;0.05). In subgroup 5B there was a drop of concentration of total cholesterol till 5.93±0.14 mmole/L (p&lt;0.001 in comparison with the first group; p&lt;0.05 in comparison with subgroup 2B); there was a decrease of lipoproteins of low density in comparison with the first group till 2.73±0.09 mmole/L (p&lt;0.001), as well as the increase of concentration of lipoproteins of high density till 2.06±0.10 mmole/L (p&lt;0.01) and triglycerides till 1.96±0.05 mmole/L (p&lt;0.01). The changes in the concentration of lipids in the serum of peripheral blood proved a very important role of the acute virus infection with 4-time growth of antibodies of IgG to CMVI in the suppression of lipid synthesis function of the liver and development of miscarriage.

Actual approaches to physical rehabilitation of patients with ischemic heart disease and complicated pathology after myocardium surgical revascularization

The aim of the research is to assess the effectiveness of restoration treatment using hydrokinesotherapy in patients with ischemic heart disease (IHD) and concomitant pathology after surgical revascularization of the myocardium (SRM).Methods of the research. 280 patients with IHD and concomitant pathology after SRM were examined. 135 patients (group 1)received the standard treatment. 145 patients (group 2) received differentiated complexes of restoration treatment depending on the concomitant pathology adding hydrokinesotherapy. The groups were divided in subgroups depending on the concomitant pathology: А – concomitant arterial hypertension, B – diabetes mellitus, C – osteoarthritis. We realized the dynamic clinical observation of the objective and subjective patients’ states, instrumental and functional methods of examination (ECG, EchoCS, Holter monitoring of ECG, measurement of arterial pressure, heart rate, veloergometry, six-minute test (SMT).Results. After the course of rehabilitation patients of all groups demonstrated the improvement, but the statistically reliable one was observed in group 2. According to the results of six-minute test of walking (SMT), the increase of the distance by 30,0, 19,6 and 30,0% was observed in subgroup 2А, 2B, 2C corresponding to (p ≤ 0,05). The reliable increase of tolerance to a physical load was observed in patients of 2 group, in subgroup А1- by 80,4, in subgroup 2B - by 62,0, and in subgroup 3B - by 32,2% (p ≤ 0,05).Conclusions. Thus, the inclusion of hydrokinesotherapy in the complex differentiated programs of rehabilitation of patients with ICD and concomitant pathology after SRM is safe and effective, moreover, it favors the myocardium contractile ability and increase of tolerance to a physical load

Problematic issues of treatment of ovarian endometriomas in women of reproductive age

Introduction. The wide spread of endometriosis disease, difficulties in diagnosing and choosing the tactics of its treatment cause the existing problems of management of endometriosis. Absence of the onset of the period of stable remission, high frequency of recurrence of the disease make it possible to consider this problem actual in the group of patients of reproductive age, and especially among women with previously realized reproductive potential, since pregnancy is considered to be the important principle of treatment of endometriosis. The aim of the study was to study the effectiveness of various treatment regimens for endometriomas in patients with previously realized reproductive potential. Materials and M ethods. 44 women aged from 17 to 49 years were examined: the first group consisted of 25 healthy nonpregnant women, the second group included 19 women, with endometriomas receiving the traditional (subgroup 2a) and complex (subgroup 2b) treatment. Results. It was revealed that in patients receiving traditional therapy, in the end of the course of treatment, the initial activation of the humoral unit of the immune system was observed, which indicated the need for immunocorrection. In patients receiving complex therapy, normalization of the body's immune homeostasis, stabilization of the processes of apoptosis and proliferation, the main links in the etiopathogenesis of endometriosis were noted, which indicated an improvement in the effectiveness of the treatment. The control ultrasound in the dynamics in 1 and 3 months in patients who continued to receive complex therapy, revealed a decrease in the size of pathological formation and a pronounced antiproliferative effect on the hyperplastically altered endometrium, diagnosed before the start of treatment in 21.05% of patients. After 3 months of treatment, there was no need for an endometrial biopsy in this group of patients. Conclusions. With the use of a comprehensive approach to the treatment of endometriomas normalization of the body's immunodeficiency parameters, regression of the endometriomas and the absence of hyperplastic endometrial processes are noted, which allows to recommend this scheme for further use.

Evaluation of Enamel Loss with Bonding and Debonding: A Study with Profile Projector

Introduction: Accidental detachment of brackets is a common problem in orthodontic bonding and removal of the residual resin certainly results in some amount of enamel loss. Aims: The present study was undertaken to measure and compare the amount of enamel loss with different prophylactic methods and to check which method results in the least amount of enamel loss. Materials and Methods: One hundred and twenty human premolars extracted for orthodontic treatment purpose were included in the study and divided into three groups of forty samples each: Group 1 (tungsten carbide bur), Group 2 (diamond bur), and Group 3 (soflex disc). The groups were further subdivided into subgroups (a and b) of twenty samples each for different etching times. The enamel loss was measured with profile projector. Results: The mean enamel loss for different subgroups was as follows - subgroup 1a tungsten carbide bur with etching time of 20 s = 69.06 μm and subgroup 1b tungsten carbide bur with etching time of 40 s = 70 μm, subgroup 2a diamond bur with etching time of 20 s = 76 μm and subgroup 2b diamond bur with etching time of 40 s = 76.12 μm, and subgroup 3a soflex disc with etching time of 20 s = 68.32 μm and subgroup 3b soflex disc with etching time of 40 s = 72.24 μm. Statistical Analysis: Analysis of variance showed a significant difference ( P t -test showed no significant difference in mean enamel loss between 20 and 40 s of etching time within groups. Conclusion: It is concluded that tungsten carbide bur resulted in the least amount of enamel loss and gouging and scarring is minimum when viewed with naked eye.

A study on validity of C-reactive protein in deciding the duration of antibiotic therapy in suspected neonatal bacterial infection

Background: Neonatal septicemia is defined as generalized bacterial infection of newborns documented by positive blood culture in first four weeks of life. Objective of present study was to determine whether C-Reactive protein can be used as a parameter to identify the time point when antibiotic treatment can safely be discontinued in a defined major subgroup of neonates treated for suspected bacterial infection.Methods: A total of 50 neonates with birth weight more than 1500gms with suspected septicemia were enrolled in the prospective study. Serum CRP were determined 24-48 hours after the first dose of antibiotics. If CRP was less than 6mg/l, infants were considered unlikely to be infected and the antibiotic treatment was stopped. If CRP was more than 6mg/l, antibiotics were continued and CRP measured on alternative days in one subgroup (2a) and on seventh day in another subgroup (2b). CRP was the single decision criterion to stop the antibiotic therapy. Negative predictive value with respect to further treatment was determined.Results: Duration of antibiotic therapy could be reduced to less than seven days in 54% cases and &lt; 72 hours in 48% cases.Conclusions: Negative predictive value of serial CRP is 100% in deciding the duration of antibiotic therapy in suspected neonatal septicemia.

The state of the local immune status, the content of neopterin and cortisol in different variants of preterm labor

Premature labour (PL) is one of the most actual and unsolved problem of obstetrics. There are many data in the li terature about the role of the disturbed ratio of pro- and antiinflammatory cytokines, neopterin in the implementation of PL. Many authors support the theory of the predominant fetus factor in the initiation of PL.&#x0D; The goal of our research is studying of the characteristics of the local immune status, neopterin and cortisol levels in various variants of preterm labour.&#x0D; Materials and methods. 77 patients were divided into 2 groups. The main group (52 pregnant women with PL) was also divided into 2 subgroups: the first (1A) subgroup consisted of 28 pregnant women with premature rupture of membranes (PROM) without regular labour contractions. Another subgroup (1B) was presented by 24 women with labour activity and unruptured amniotic sac (true PL). In the control group we included 25 women with term labour. The level of the expression of mRNA genes of a congenital immunity in a cervical canal by the test-system ImmunoQuantex (IL1B, IL10, IL18, TNF2, TLR4, GATA3, CD68, B2M), as well as serum levels of neopterin and cortisol. The results were analyzed by standard statistical methods.&#x0D; Results. There were no significant difference in the expression levels of most of the genes of innate immunity between the study groups (p &gt; 0.05). The investigation of expression of TLR4, GATA3 genes in different types of PL revealed a significant decrease (p &lt; 0.05) in patients with PROM (1A subgroup). In addition in the 1A subgroup the inflammation index was higher (Me = 99,5%, p &lt; 0.01). There were no fundamental difference in the state of the local immune status between groups of true preterm and term labour. Analysis of neopterin content among the subjects showed a significant increase in the main group (PL) compared with the control group (p = 0.0064). The comparison of the neopterin level between different variants of PL had a higher index (p &lt; 0.025). The concentration of cortisol in the study groups had no principle difference from the main (PL) group and control group (p &gt; 0.05). The maximum cortisol level was found in the subgroup 1B (true PL), which is significantly higher than in the subgroup 1A (with PROM) and in the control group (p &lt; 0.01).&#x0D; Conclusion. The difference in the state of local immune status in different variants of premature labour demonstrates different mechanisms of initiation of preterm labour. It is likely that the ratio of TLR4/GATA3 and index of inflammation determins the onset of preterm labour. The level of neopterin can be used as a marker of the onset of PL. The increase of cortisol determines the role of the fetus factor in the onset of labour.

Structure-activity relationship study and optimisation of 2-aminopyrrole-1-benzyl-4,5-diphenyl-1H-pyrrole-3-carbonitrile as a broad spectrum metallo-β-lactamase inhibitor

A SAR study on derivatives of 2-amino-1-benzyl-4,5-diphenyl-1H-pyrrole-3-carbonitrile 5a revealed that the 3-carbonitrile group, vicinal 4,5-diphenyl and N-benzyl side chains of the pyrrole are important for the inhibitory potencies of these compounds against members representing the three main subclasses of metallo-β-lactamases (MBLs), i.e. IMP-1 (representing the B1 subgroup), CphA (B2) and AIM-1 (B3). Coupling of 5a with a series of acyl chlorides and anhydrides led to the discovery of two N-acylamide derivatives, 10 and 11, as the two most potent IMP-1 inhibitors in this series. However, these compounds are less effective towards CphA and AIM-1. The N-benzoyl derivative of 5a retained potent in vitro activity against each of MBLs tested (with inhibition constants in the low μM range). Importantly, this compound also significantly enhanced the sensitivity of IMP-1, CphA- or AIM-1-producing cell cultures towards meropenem. This compound presents a promising starting point for the development of a universal MBL inhibitor, targeting members of each of the major subgroups of this family of enzymes.

ABCA1 gene polymorphism and oxidative stress in polycystic ovary syndrome: Role of antioxidant therapy for prevention and control

Polycystic ovary syndrome (PCOS) is a common health problem that affects women in childbearing age. Recent studies discussed the relation of oxidative stress with PCOS and suggested that the antioxidants may improve the prognosis of PCOS. Changes happened in ATP binding cassette transporter 1 (ABCA1) gene encoding a protein regulating entry and exit from cell membrane may contribute to dyslipidemia in patients with PCOS. The role of oxidative stress and ABCA1 gene polymorphism in the pathogenesis of PCOS was evaluated along with the effect of antioxidants in the prevention and treatment of this disease. The present study included 90 female patients with PCOS and 90 healthy women represented the control group. Patients with PCOS were further divided into two subgroups. The patients included in subgroup 1a were treated with antioxidant and hormonal therapy while patients included in subgroup 1b were treated with hormonal therapy only. ABCA1gene polymorphism and oxidative stress parameters were investigated in all groups. The level of the oxidant marker; MDA was higher in PCOS patients when compared to controls. In addition, the levels of GSH, vitamin E, ascorbic acid, and selenium were significantly decreased, while SOD and GPx activities were increased in PCOS patients when compared to controls. The response to treatment among PCOS patients was better in group 1a than group 1b. The frequency of ABCA1 AA genotype was higher in PCOS patients than the control group (32.2% and 11.1% respectively). It was concluded that oxidative stress may lead to PCOS which raises the possibility of using antioxidants for the prevention and control of PCOS. In addition, the polymorphism in ABCA1 gene may be associated with genetic susceptibility for PCOS.

Is the presence of end-diastolic forward flow specific for restrictive right ventricular physiology in repaired tetralogy of Fallot?

BackgroundEnd-diastolic forward flow (EDFF) is recognized as restrictive right ventricular physiology (r-RVP), but conflicting results have been reported about effects on the clinical outcome in repaired tetralogy of Fallot (r-TOF). ObjectivesWe hypothesized that the EDFF by Doppler was not specific for diagnosing r-RVP. MethodsSixty-two consecutive patients aged 15.7±11.6years who underwent cardiac catheterization were studied. Patients were divided according to the presence of EDFF (group 1: EDFF+, group 2: EDFF−) and RV size (group A: small RV, group B: large RV [>150ml/m2]). ResultsGroup 1 (n=23) had higher a right atrial pressure (RAP), pressure gradient between the RAP and pulmonary diastolic pressure (PDP), and atrial natriuretic peptide (ANP) levels than group 2. Four patients (17.4%) in group 1 and 89.7% of patients in group 2 had a normal RAP range (a wave<10mmHg). There were no differences in the RV volume, ejection fraction (EF), B-type natriuretic peptide levels, and severity of pulmonary regurgitation (PR) between groups 1 and 2. Group A had better RV and LVEF than group B, as well as a smaller LV size. The RAP in subgroup 1A was higher than that of the other 3 subgroups. Subgroup 1B had a similar RAP to group 2, and a lower PDP and a more severe PR than subgroup 1A. ConclusionsPatients with EDFF are associated with increased ANP levels. The presence of EDFF may not be specific for r-RVP, since it is observed in some TOF patients with low PDP (severe PR) and normal RAP.

MP40-17 PROSPECTIVE RANDOMIZED COMPARISON OF REPAIRING SIMPLE VESICOVAGINAL FISTULA WITH OR WITHOUT INTERPOSITION FLAP: A TERTIARY CARE HOSPITAL STUDY FROM NOTHERN INDIA

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Female Incontinence: Therapy I1 Apr 2017MP40-17 PROSPECTIVE RANDOMIZED COMPARISON OF REPAIRING SIMPLE VESICOVAGINAL FISTULA WITH OR WITHOUT INTERPOSITION FLAP: A TERTIARY CARE HOSPITAL STUDY FROM NOTHERN INDIA Vishwajeet Singh, RahulJanak Sinha, Ankur Bansal, Seema Mehrotra, and Kawaljit Singh Vishwajeet SinghVishwajeet Singh More articles by this author , RahulJanak SinhaRahulJanak Sinha More articles by this author , Ankur BansalAnkur Bansal More articles by this author , Seema MehrotraSeema Mehrotra More articles by this author , and Kawaljit SinghKawaljit Singh More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1264AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Outcome assessment of simple vesicovaginal fistula (VVF) repair with or without the use of interposition flaps. METHODS This prospective randomised study was conducted between 2012 to 2015 in department of Urology King George’s Medical University, Lucknow. Obstetric and gynaecologic fistula less than 4 cm were included. Those with complex or complicated fistula and fistula due to malignancy were excluded from this study. Patients were divided into two groups (group 1 and group 2) depending upon route of repair i.e. transvaginal or transabdominal respectively as per characteristics and location of fistula. These two groups were randomised into two subgroups (1A, 1B and 2A, 2B) based on with use and without use of interposition flap during fistula repair. Perioperative and post-operative parameters (blood loss, mean operating time, hospital stay, requirement of analgesics) were compared. All complications occurred in postoperative period till last follow –up were recorded and Clavien Dindo Classification was used to stratify them. RESULTS Fifty-four patients underwent transvaginal repair- group 1 (27 with Martius flap-group 1A and 27 with no Martius flap – group 1B). Sixty-six patients underwent transabdominal repair-group 2 (33 with interposition flap- group 2A and 33 with no flap – group 2B). Blood loss, mean operating time, hospital stay, requirement of analgesics were comparable between sub-group 1A versus 1B; and 2A versus 2B. Overall success rate of repair across all groups was 92.7% (115/124). Success rate was 88.9% in transvaginal repair with martius flap versus 92.6 % in transvaginal repair with no flap (P=1.0) and it was 93.9 % in both subgroups of transabdominal repair (P=1.0). Mean follow up period was 33.6 months (range 12-46). 9 out of 27 patients (33.3%) with Martius flap interposition had significantly reduced sensation on labia majora. Of these 9 patients, 5 cases reported numbness and 4 had pain compared to patients in group IB who did not report any altered sensation in labia. (P = 0.001). CONCLUSIONS The success rates are similar in simple VVF repair irrespective of the use of interposition flaps. However, overall morbidity following repair with interposition flap is more when compared with repair without interposition flap either by transvaginal or by transabdominal route. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e529 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Vishwajeet Singh More articles by this author RahulJanak Sinha More articles by this author Ankur Bansal More articles by this author Seema Mehrotra More articles by this author Kawaljit Singh More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

COMPARATIVE ASSESSMENT OF REMOTE RESULTS OF NON-PHARMACOLOGICAL METHODS OF COMPLEX TREATMENT OF OBLITERATING ATHEROSCLEROSIS OF THE LOWER EXTREMITIES IN PATIENTS OF ELDERLY AND SENILE AGE

Aim - to estimate the remote results of treatment of obliterating atherosclerosis of arteries of the lower extremities of the II stage in patients of advanced and senile age after the combined use of ozone therapy and gravitational therapy. Materials and methods. A prospective randomized study in three parallel groups comprised 139 patients. The first group (n = 57) received standard medical therapy in combination with ozone therapy; the group was divided into two subgroups: the patients of subgroup 1a (n = 28) received intravenous ozonated physiological solution, in subgroup 1b (n = 29) - major ozonated autohemotherapy (MOA). Patients of the second group (n = 62) underwent comprehensive treatment, including gravitational therapy (GT) in addition to medical ozone. In this group we also identified two subgroups: subgroup 2a (n = 31), in which the patients received standard medical therapy in combination with ozonated physiological solution and gravitational therapy, and subgroup 2b (n = 31), in which the treatment was amplified by MOA and GT. The third group was the control group (n = 20) that included patients who received only standard medical therapy. Dynamics of changes of disease stages and the number of surgeries in the remote period was estimated (up to 7 years). Results. After 6 months of follow-up observation, the distribution of the disease stages among the patients did not differ significantly (p&gt; 0.05) from the initial amount. Analysis of survival and probable risks after 7 years of follow-up by Cox regression method in relation to the applied method of treatment revealed maximum efficiency of combined treatment in subgroup 2a. Conclusion. As a result of complex conservative treatment, including ozonotherapy and gravitational therapy, the probability of surgical interventions as well as disease stage advancing were effectively reduced.

Sybr Green- and TaqMan-Based Quantitative PCR Approaches Allow Assessment of the Abundance and Relative Distribution of Frankia Clusters in Soils.

The nodule-forming actinobacterial genus Frankia can generally be divided into 4 taxonomic clusters, with clusters 1, 2, and 3 representing nitrogen-fixing strains of different host infection groups and cluster 4 representing atypical, generally non-nitrogen-fixing strains. Recently, quantitative PCR (qPCR)-based quantification methods have been developed for frankiae of clusters 1 and 3; however, similar approaches for clusters 2 and 4 were missing. We amended a database of partial 23S rRNA gene sequences of Frankia strains belonging to clusters 1 and 3 with sequences of frankiae representing clusters 2 and 4. The alignment allowed us to design primers and probes for the specific detection and quantification of these Frankia clusters by either Sybr Green- or TaqMan-based qPCR. Analyses of frankiae in different soils, all obtained from the same region in Illinois, USA, provided similar results, independent of the qPCR method applied, with abundance estimates of 10 × 105 to 15 × 105 cells (g soil)-1 depending on the soil. Diversity was higher in prairie soils (native, restored, and cultivated), with frankiae of all 4 clusters detected and those of cluster 4 dominating, while diversity in soils under Alnus glutinosa, a host plant for cluster 1 frankiae, or Betula nigra, a related nonhost plant, was restricted to cluster 1 and 3 frankiae and generally members of subgroup 1b were dominating. These results indicate that vegetation affects the basic composition of frankiae in soils, with higher diversity in prairie soils compared to much more restricted diversity under some host and nonhost trees.IMPORTANCE Root nodule formation by the actinobacterium Frankia is host plant specific and largely, but not exclusively, correlates with assignments of strains to specific clusters within the genus. Due to the lack of adequate detection and quantification tools, studies on Frankia have been limited to clusters 1 and 3 and generally excluded clusters 2 and 4. We have developed tools for the detection and quantification of clusters 2 and 4, which can now be used in combination with those developed for clusters 1 and 3 to retrieve information on the ecology of all clusters delineated within the genus Frankia Our initial results indicate that vegetation affects the basic composition of frankiae in soils, with higher diversity in prairie soils compared to much more restricted diversity under some host and nonhost trees.