Phosphocreatine Attenuates Isoproterenol-Induced Cardiac Fibrosis and Cardiomyocyte Apoptosis

The present study was designed to further explore the role and the underlying molecular mechanism of phosphocreatine (PCr) for cardiac fibrosis in vivo. Isoproterenol (ISO) was used to induce cardiac fibrosis in rats. PCr administration ameliorated fibrosis by reducing collagen accumulation and fibrosis-related signals, including transforming growth factor beta 1 (TGF-β1), alpha smooth muscle actin (α-SMA), collagen type I, and collagen type III. Mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathways, including p38, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p65, were highly activated by ISO and blocked by PCr. Moreover, PCr decreased ISO-induced matrix metalloproteinase-9 (MMP-9) and increased the tissue inhibitor of metalloproteinase-1 (TIMP-1) expression. Furthermore, PCr suppressed cardiomyocyte apoptosis induced by ISO, as shown by downregulated expression of the proapoptotic caspase-3, Bax, and upregulated expression of the antiapoptotic Bcl-2. Taken together, PCr can be an effective agent for preventing cardiac fibrosis and cardiomyocyte apoptosis.

http://bit.ly/2RAGOvv

Mitochondria, Apoptosis and Cancer (MAC) 2017

Authors: Turk, Boris


http://bit.ly/2sg29fK

Nuclear Medicine

Distribution of bone tracer uptake in symptomatic knees after ACL reconstruction compared to asymptomatic non-operated knees: a method for better differentiating patient-specific from disease-specific bone tracer uptake in SPECT/CT Abstract Objective To evaluate the differences of bone tracer uptake (BTU) in symptomatic and asymptomatic contralateral knees in patients after reconstruction of the anterior cruciate ligament (ACL-R) and to identify typical BTU patterns and threshold values to differentiate pathological from physiological BTU. Methods 53 patients after unilateral ACL-R were retrospectively included in the study. The population was subdivided into a group of symptomatic operated knees and a group of contralateral asymptomatic non-operated knees. BTU was measured in SPECT/CT using a validated anatomical localization-scheme and normalized mean BTU values were calculated in both knees. Wilcoxon signed rank-test and Pearson's rank-correlation coefficient were used (p < 0.05). Results Symptomatic knees after ACL-R showed significantly more BTU than asymptomatic ones (p < 0.01).Based on the measured BTU activity in SPECT/CT in symptomatic operated and asymptomatic non-operated knees, intensity thresholds of pathological BTU were established. A BTU threshold of greater than the Median + 1 SD of the asymptomatic non-operated knee was defined as pathological. In both groups the highest mean BTU was found on the femoral, tibial and patellar articular surfaces, the lowest BTU in femoral and tibial regions far from the joint. Conclusions The established BTU thresholds for SPECT/CT in knees after ACL-R help to differentiate disease-specific from patient-specific BTU. It could be speculated that BTU in asymptomatic knees equates to the preoperative condition of the knee joint before ACL-R. Therefore, the results of this study help to understand in-vivo loading of the knee and ultimately lead to prediction of development of osteoarthritis in an early stage.

18 F-DOPA uptake does not correlate with IDH mutation status and 1p/19q co-deletion in glioma Abstract Objective The role of amino acid positron emission tomography (PET) in glioma grading and outcome prognostication has not yet been well established. This is particularly true in the context of the new WHO 2016 classification, which introduced a definition of glioma subtypes primarily based on molecular fingerprints. The aim of the present study was to correlate 3,4‑dihydroxy‑6‑[18F]‑fluoro-l‑phenylalanine (F-DOPA) uptake parameters with IDHmutation, 1p/19q status, and survival outcomes in patients with glioma. Methods The study population consisted of 33 patients (17 M/16 F, mean age: 46 ± 13 years) who underwent F-DOPA PET/CT for the evaluation of tumor extent before the start of chemo or radiotherapy. The presence of IDHmutation and 1p/19q status was assessed in all the cases. Tumor volume and semiquantitative uptake parameters, namely SUVmax, tumor-to-normal brain ratio and tumor-to-normal striatum ratio, were calculated for each tumor. Imaging-derived parameters were compared between patients stratified according to molecular fingerprints, using parametric or non-parametric tests, where appropriate. The Kaplan–Meier method was used to assess differences of overall survival (OS) and progression-free survival (PFS) between groups. PET parameters were also tested as prognostic factors in univariate Cox survival regression models. Results There were 12 IDH-wild-type and 21 IDH-mutant patients. Stratification according to 1p/19q co-deletion resulted in 20 non-co-deleted and 13 co-deleted patients. Median follow-up time from PET/CT exam was 30.5 months (range 3.5–74 months). Semiquantitative uptake parameters did correlate neither with IDH mutation nor with 1p/19q status. Uptake was similar in low-grade and high-grade tumors, respectively. In addition, F-DOPA uptake parameters, macroscopic tumor volume, or tumor grade did not stratify OS, while a correlation between SUVmax and PFS was shown in the subgroup of astrocytomas. On the other hand, IDH mutation status and presence of 1p/19q co-deletion had a significant impact on survival outcomes. The prognostic value of IDH mutation status was also confirmed in the subgroup of patients with astrocytic tumors. Conclusions F-DOPA uptake parameters do not correlate with tumor molecular and histological characteristics. The predictive value of PET-derived parameters on outcomes of survival is limited.

Fundamental study of radiogallium-labeled aspartic acid peptides introducing octreotate derivatives Abstract Objective Somatostatin receptors are highly expressed in neuroendocrine tumors, and many radiolabeled somatostatin analogs for diagnosis and treatment have been developed. To simultaneously detect not only primary cancer but also bone metastases, this study aimed to develop a positron emission tomography probe using generator-produced nuclide Gallium-68 (T1/2 = 68 min), in which a carrier for primary cancer, a carrier for bone metastases lesions, and a stable gallium complex are introduced into the one molecule. Based on this strategy, the somatostatin receptor-targeted peptide, [Tyr3]-octreotate (TATE), aspartic acid peptide (Dn) with high binding affinity for hydroxyapatite, and Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) as a stable gallium complex were selected. The novel complexes, Ga-DOTA-Dn-TATE (n = 0, 2, 5, 8, or 11), were designed, synthesized, and evaluated. The radiogallium complexes were prepared using the easy-to-handle radioisotope 67Ga due to relatively long half-life. Methods The radiogallium complex precursor DOTA-Dn-TATE was synthesized by the Fmoc-based solid-phase method and by the air oxidation method to form the disulfide bond. [67Ga]Ga-DOTA-Dn-TATE was synthesized by reacting DOTA-Dn-TATE and 67Ga. Hydroxyapatite binding assays, in vitro cellular uptake experiments in AR42J tumor cells, in biodistribution experiments in AR42J tumor-bearing mice, were performed using [67Ga]Ga-DOTA-Dn-TATE. Results The radiochemical purities of [67Ga]Ga-DOTA-Dn-TATE were > 96.0%. In in vitro and in vivo experiments, [67Ga]Ga-DOTA-D11-TATE had a high affinity for hydroxyapatite and highly accumulated in bone. However, the uptake of [67Ga]Ga-DOTA-D11-TATE into somatostatin receptor-positive AR42J cells was lower than that of [67Ga]Ga-DOTA-TATE, and the accumulation of [67Ga]Ga-DOTA-D11-TATE in tumor was significantly low. Conclusion Ga-DOTA-D11-TATE may not be recognized by somatostatin receptor by the introduction of D11, and the charge adjustment may be important for somatostatin receptor-positive cell uptake.

Brain 18 F-FDG distribution: which region is most affected by increased plasma glucose levels?

Clinical feasibility of early scanning after administration of 68 Ga-DOTATOC Abstract Objective Positron emission tomography (PET)/computed tomography (CT) using 68Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid-d-Phe1-Tyr3-octreotide (DOTATOC) is usually performed about 1-h post-injection; however, because of rapid blood clearance, the waiting time for scanning could possibly be shortened without affecting diagnostic performance. The purpose of this study was to investigate the feasibility of early scanning at 30 min post-injection. Methods Thirty-eight patients who underwent DOTATOC-PET/CT were analyzed. After administration of 68Ga-DOTATOC, data acquisition was performed twice, at 30-min and 60-min post-injection. The number of known or suspected pathological lesions, and quantitative values of those lesions and physiological uptake were compared. SUVmax, SUVpeak, metabolic tumor volume (MTV), and total lesion uptake (TLU) were calculated as quantitative values of the pathological lesions. Results A total of 125 known or suspected pathological lesions were found at both timepoints, with no differences between the two datasets. The SUVmax, SUVpeak, MTV, and TLU were highly reproducible, with Spearman's ρ of 0.983, 0.986, 0.918, and 0.981, respectively. The average percent differences (%DIFFave) defined as the differences of the values divided by the value at 1-h post-injection were 11.1% for SUVmax, 8.5% for SUVpeak, 15.1% for MTV, and 20.6% for TLU. Physiological uptake in the two datasets was closely comparable in the pituitary gland (Spearman's ρ = 0.954, %DIFFave = 11.0%), liver (0.989, 3.9%), spleen (0.970, 6.3%), adrenal glands (0.879, 13.0%), and pancreatic uncus (0.946, 12.7%). Conclusion The diagnostic performance of visual interpretation should be comparable between DOTATOC-PET/CT images obtained at 30-min and 60-min post-injection. Some differences between quantitative values may exist; however, they appear to be minimal.

Techniques for generating attenuation map using cardiac SPECT emission data only: a systematic review Abstract To reliably interpret and perform quantitative analysis, attenuation correction for cardiac single-photon emission computed tomography (SPECT) is fundamental. Thus, knowledge of the patient-specific attenuation map for accurate correction is required in SPECT quantitative imaging. The aim of this systematic review is to present general principles of attenuation correction and provide a structured summary of the approaches that have been proposed for generating the attenuation map for cardiac SPECT. We identified relevant articles published in English pertaining to the attenuation map (AM) determination using SPECT emission data only by searching PubMed, EMBASE, Scopus, and Web of Science databases. Moreover, other articles were hand searched. The protocol of this systematic review was registered in PROSPERO and the code given is CRD42017060512. Transmissionless techniques of determining attenuation map including calculated methods, statistical modeling for simultaneous estimation of attenuation and emission, consistency conditions criteria, using scattered data and other methods were reviewed. Methods for performing attenuation map for cardiac SPECT are developing and the progresses made are promising. However, much work is needed to assess the efficacy of the correction schemes in the clinical routine.

The significant value of predicting prognosis in patients with colorectal cancer using 18 F-FDG PET metabolic parameters of primary tumors and hematological parameters Abstract Objects The purpose was to evaluate the correlation of the pre-treatment hematological parameters with metabolic parameters of primary tumor in baseline 18F-FDG PET/CT in patients with colorectal cancer (CRC) and estimate the prognostic value of both. Methods We retrospectively investigated 231 patients with CRC who underwent baseline 18F-FDG PET/CT. Routine blood sampling was tested in the same term. PET parameters in term of hematological parameters and pathological characteristics of primary tumor were compared. Kaplan–Meier survival analysis was performed in the patients without distant metastasis. The differences of disease-free survival between groups were compared by log-rank tests. Results Neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) were significantly correlated with all the metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG). The patients with NLR > 3 had higher MTV (24.82 ± 18.16 vs 19.06 ± 13.30, P = 0.039) and TLG (219.04 ± 186.94 vs 166.45 ± 146.39, P = 0.047) than those whose NLR ≤ 3. NLR in those patients with distant metastasis was significantly higher than those without distant metastasis (P = 0.018) while LMR in those patients with distant metastasis was significantly lower than those without distant metastasis (P = 0.032). Survival analysis showed that those patients with low MTV (P = 0.015), low NLR (P = 0.008) and high LMR (P = 0.027) revealed significant survival benefit. Conclusions There was a significant association between the pre-treatment hematological parameters and metabolic parameters of baseline 18F-FDG PET/CT in the patients with CRC. It might be helpful in those patients with high NLR and low LMR to undergo 18F-FDG PET/CT to detect distant metastasis and predict prognosis.

Comparison of 18 F-Choline PET/CT and MRI functional parameters in prostate cancer Abstract Aim 18F-Choline (FCH) uptake parameters are strong indicators of aggressive disease in prostate cancer. Functional parameters derived by magnetic resonance imaging (MRI) are also correlated to aggressive disease. The aim of this work was to evaluate the relationship between metabolic parameters derived by FCH PET/CT and functional parameters derived by MRI. Materials and methods Fourteen patients with proven prostate cancer who underwent FCH PET/CT and multiparametric MRI were enrolled. FCH PET/CT consisted in a dual phase: early pelvic list-mode acquisition and late whole-body acquisition. FCH PET/CT and multiparametric MRI examinations were registered and tumoral volume-of-interest were drawn on the largest lesion visualized on the apparent diffusion coefficient (ADC) map and projected onto the different multiparametric MR images and FCH PET/CT images. Concerning the FCH uptake, kinetic parameters were extracted with the best model selected using the Akaike information criterion between the one- and two-tissue compartment models with an imaging-derived plasma input function. Other FCH uptake parameters (early SUVmean and late SUVmean) were extracted. Concerning functional parameters derived by MRI scan, cell density (ADC from diffusion weighting imaging) and vessel permeability (Ktrans and Ve using the Tofts pharmakinetic model from dynamic contrast-enhanced imaging) parameters were extracted. Spearman's correlation coefficients were calculated to compare parameters. Results The one-tissue compartment model for kinetic analysis of PET images was selected. Concerning correlation analysis between PET parameters, K1 was highly correlated with early SUVmean (r = 0.83, p < 0.001) and moderately correlated with late SUVmean (r = 0.66, p = 0.010) and early SUVmean was highly correlated with late SUVmean (r = 0.90, p < 0.001). No significant correlation was found between functional MRI parameters. Concerning correlation analysis between PET and functional MRI parameters, K1 (from FCH PET/CT imaging) was moderately correlated with Ktrans (from perfusion MR imaging) (r = 0.55, p = 0.041). Conclusions No significant correlation was found between FCH PET/CT and multiparametric MRI metrics except FCH influx which is moderately linked to the vessel permeability in prostate cancer.

Count-based method for specific binding ratio calculation in [I-123]FP-CIT SPECT analysis Abstract Objective To calculate the specific binding ratio (SBR) appropriately in dopamine transporter (DAT) imaging, a method for extracting the striatal volume of interest (VOI) was developed. Methods This study included 200 patients (72 ± 10 years) who were suspected of parkinsonian syndromes (PS) or dementia with Lewy body (DLB). The patients were divided into three groups of PS with dopaminergic degeneration, DLB and non-PS after [123I]ioflupane (FP-CIT) SPECT and clinical follow-up. The image data were reconstructed with CT attenuation correction and scatter correction, and with only CT attenuation correction (CTAC). The new method extracted striatal VOI according to the high-level counts and the average striatum volume, and calculated SBR using the reference occipital counts. The SBR values for each patient were obtained using the Tossici-Bolt method (SBRBolt) and our method. Reproducibility of SBR calculation using our method was compared by two operators. Results The mean SBR values for the PS and DLB groups were significantly different from that of the non-PS group with both methods. The coefficients of variation of the SBR were significantly smaller with the proposed method compared with those of SBRBolt (p < 0.001), except for the CTAC images. There were no differences in SBR between the two operators using our method. The diagnostic accuracies with our method for the PS and DLB groups were 98.4 and 96.0%, respectively. Conclusion Our new method for SBR calculation in the FP-CIT SPECT showed less coefficients of variation with high reproducibility, which would be useful for clinical diagnosis and in assessing the severity of diseases in follow-up studies.

The role of 13 N -ammonia in the differential diagnosis of gliomas and brain inflammatory lesions Abstract Objective To investigate the utility of 13N-ammonia PET/CT imaging in the differential diagnosis of gliomas and brain inflammations. Methods 13N-ammonia PET/CT imaging data of 77 patients with gliomas and 34 patients with brain inflammations were retrospectively analyzed. No patients received any treatment before 13N-ammonia imaging. All the patients were diagnosed by stereotactic biopsy or clinical follow-up. Visual and semi-quantitative analysis was performed to analyze the results of 13N-ammonia imaging. Finally, the uptake ratios of each lesion were calculated and its differences among different groups were tested with one-way ANOVA. Results 29.4% inflammations, 51.6% low-grade gliomas and 91.3% high-grade gliomas were positive by visual analysis in 13N-ammonia imaging. The sensitivity, specificity and accuracy for the diagnosis of gliomas were 75.3%, 55.8% and 67.8%, respectively. As for semi-quantitative analysis, the T/G ratios of inflammatory lesions, low-grade gliomas and high-grade gliomas were 0.88 ± 0.24, 1.04 ± 0.43 and 1.43 ± 0.49, respectively. One-way ANOVA revealed that the T/G ratios of high-grade gliomas were significantly higher than those of low-grade gliomas and inflammations (P < 0.05), but there was no statistical difference between low-grade gliomas and inflammations (P = 0.118). Among the inflammatory lesions, T/G ratios were not statistically different between infectious and demyelinating lesions (P > 0.05). ROC curve analysis showed that the optimal cut-off value of T/Gratio in distinguishing gliomas from inflammations was 1.21 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 52.9%, 94.4%, 65.3%, 95.7% and 45.9%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas was 1.06 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 81.5%, 67.7%, 76.5%, 81.5% and 67.7%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas and inflammations was 1.19 with the AUC 0.84. The sensitivity, specificity, accuracy, PPV and NPV were 70.4%, 85.1%, 78.5%, 79.2% and 78.1%, respectively. Conclusions 13N-ammonia imaging is effective in distinguishing high-grade gliomas from low-grade gliomas and inflammations, but its role in the differential diagnosis of low-grade gliomas and brain inflammatory lesions is limited, and the accuracy needs to be improved.

Dental Research

Load-deflection characteristics of coated and noncoated nickel-titanium wires in self-ligating brackets using a modified bending test: An in vitro study Tripti Tikku, Rohit Khanna, Akhil Agarwal, Kamna Srivastava, Shashank Shekhar, Ivy Shukla Dental Research Journal 2019 16(1):1-6 Background: To determine and compare the force-deflection values of different types of nickel-titanium (NiTi) wires during unloading phase at varying deflections, that is 1 mm, 1.5 mm, 2 mm, and 2.5 mm, with the use of self-ligating ceramic brackets using modified bending test on a typodont under controlled temperature conditions. Materials and Methods: In this in vitro study total of 45 wires of ovoid shape of three different NiTi wires – pseudoelastic NiTi (Group I), heat activated NiTi (Group II), and esthetic coated NiTi (Group III) for maxillary arch were tested after insertion in ceramic self-ligating brackets bonded to plastic teeth of phantom jaw . The maxillary left lateral incisor was removed to simulate a malpositioned tooth which acted as the load site, and load-deflection characteristics were measured during unloading using Instron, and data analyzed statically by two-way analysis of variance ,Tukey's post hoc test, intraclass correlation coefficient and Pearson correlation coefficient. A two-sided (α = 2) P < 0.05 was considered statistically significant. Results: When wires were compared at each deflection statistically significant difference was observed between the three groups of wires (Group I > Group II > Group III) at all the four levels of deflection except for Group II versus Group III at 1 mm, 1.5 mm, and 2 mm of deflection. Statistically significant difference was noted in mean load values for comparisons made at different deflections for each wire except for the comparison made at 1.5 versus 2 mm for Group II and Group III. Conclusion: Overall comparison showed esthetic coated Ni-Ti wires gave significantly lower mean load values, followed by heat activated and pseudoelastic NiTi wires. Thus, heat activated NiTi wires are best suited in patients with severe malpositions/periodontitis, while for esthetically conscious patients esthetic coated NiTi can be used.

Effects of menthol-flavored substances at the cellular level on oral mucosal sites Nanda Prasad, Sarvesh Vijay, A Yashwanth Reddy, S Nonitha Dental Research Journal 2019 16(1):7-11 Background: The purpose of this study was to determine the effects of menthol-flavored substances at the cellular level in different mucosal sites of the oral cavity and to compare the cellular changes between individuals without the habit of chewing menthol-flavored substances and individuals with the habit. Materials and Methods: This was an experimental cytology study including a total of 500 individuals belonging to the age group of 18–45 years based on the inclusion or exclusion criteria. The selected participants were divided into two groups of 250 participants each, based on participants not having the habit of chewing menthol-flavored substances (Group I) and participants having the habit of chewing menthol-flavored substances (Group II). Cytological smears were taken by gently scraping the mucosal surfaces in different sites of the oral mucosa using a wooden spatula and stained with Papanicolaou, analyzed under microscope for any cellular changes. The results were tabulated and statistically analyzed using Chi-square test and Fisher's exact test. P < 0.05 was considered statistically significant. Results: Micronuclei seen in all the participants belonging to group with the habit of chewing menthol-flavored substances with a P < 0.001 which was considered highly significant. Alteration in the nuclear-cytoplasmic ratio was also seen P = 0.001, which showed significant at 1% significance level. Conclusion: Participants with habit of chewing menthol-flavored substances showed the presence of micronuclei and slight alteration in the nuclear-cytoplasmic ratio, which could be directly related to genotoxicity and cell damage.

Impact of occupational dental erosion on oral health-related quality of life among battery factory workers in Bengaluru, India Amit Kumar, Manjunath P Puranik, KR Sowmya, Soni Rajput Dental Research Journal 2019 16(1):12-17 Background: A greater understanding of impact of occupational dental erosion on oral health-related quality of life (OHRQoL) will sensitize both employee and employers to adopt strict protective measures for oral health. The research aimed to determine the relationship between occupational dental erosion and OHRQoL among battery and other factory workers in Bengaluru, India. Materials and Methods: This cross-sectional comparative study enrolled a total of 400 workers. Structured proforma assessed information on sociodemographic details, oral hygiene practices, adverse oral habits, and work-related practices. OHRQoL was determined using oral health impact profile-14 (OHIP-14). Dental erosion was measured using Smith and Knight's tooth wear index modified by Millward et al. 1994 scoring system independent t-test, Mann–Whitney U-test and Spearman's correlation was performed. P < 0.05 was considered statistically significant. Results: The mean age of the participants in the study and control groups was 43.11 ± 8.02 and 45.93 ± 6.16 years, respectively. Less than half of the participants in the study group had positive behavioral work practice. The prevalence and severity of dental erosion was significantly higher in study group (39.5%) than control group (11.5%). Mean OHIP-14 score was significantly lower in study group (23.88 ± 0.88) than control group (26.06 ± 9.67). Dental erosion significantly correlated with work experience and OHIP-14. Conclusion: The findings highlight the impact of occupational dental erosion on OHRQoL. Measures to enhance occupational safety thereby reducing exposure to occupational hazards are needed.

Comparative investigation of primary stability of four different dental implants in low-density bone model Saied Nokar, Amirali Reza Rasouli-Ghahroudi, Elham Shidvash, Faezeh Atri Dental Research Journal 2019 16(1):18-23 Background: Primary stability is one of the prerequisites of immediate loading. The aim of this study was to compare the primary stability of four different implant systems in low-density bone models. Materials and Methods: In this in vitro experimental study, 20 fixtures from four implant body designs were selected: Zimmer Tapered Screw-Vent (ZTSV), NobleReplace Tapered (NRT), Replace Select Tapered (RST), and Dentium SuperLine (DSL). Fixtures were inserted in low-density bone models according to manufacturer drilling protocol by one surgeon. Measurement of insertion torque value (ITV), resonance frequency analysis (implant stability quotient [ISQ]), and reverse torque value (RTV) was recorded for each fixture. The data were analyzed with one-way ANOVA and post hoc tests (Tukey honestly significant difference) (P < 0.05). Results: ZTSV had significantly lower amount of insertion torque in comparison to other systems (P = 0.045). RTV was significantly lower in ZTSV in comparison to DSL and NRT (P = 0.004). ISQ value in NRT (ISQ = 67) was significantly higher than other systems (P = 0.000). The lowest amount of ISQ was in RST system (ISQ = 53) with significant difference (P = 0.000). Conclusion: This study demonstrated that primary stability of different implant systems was not comparable and implant design was effective on ITV, RTV, and ISQ.

Assessment of antimicrobial activity of different concentrations of Tinospora cordifolia against Streptococcus mutans: An in vitro study Sankalp Agarwal, Priyadarshini H Ramamurthy, Bennete Fernandes, Avita Rath, Preena Sidhu Dental Research Journal 2019 16(1):24-28 Background: The antimicrobial property of Tinospora cordifolia has been tested against a variety of microorganisms in the literature. The present study aimed to assess the antimicrobial activity of different concentrations of commercially available T. cordifolia powder against Streptococcus mutans. Materials and Methods: An in vitro study was undertaken in which extract of T. cordifolia was obtained using 100% ethanol by maceration. Seven different concentrations were prepared and tested against S. mutans in brain–heart infusion agar medium. Plates were incubated aerobically at 37°C for 48 h, and zone of inhibition was measured using Vernier caliper. 0.2% chlorhexidine and dimethylformamide were used as positive and negative controls respectively. The data were analysed by descriptive analytic tests. Results: The maximum antibacterial activity of T. cordifolia was observed with a volume of 40 μl at 2% concentration with a zone of inhibition of 19 mm. A 30 μl volume of 0.2% chlorhexidine showed a zone of inhibition of 28 mm, and no zone of inhibition was observed with dimethylformamide. Conclusion: Tinospora exhibited antimicrobial activity against S. mutans. However, it needs to be confirmed further with in vivo studies.

Association between quality of sleep and chronic periodontitis: A case–control study in Malaysian population Vijendra Pal Singh, Joe Yin Gan, Wei Ling Liew, Htoo Htoo Kyaw Soe, Sowmya Nettem, Sunil Kumar Nettemu Dental Research Journal 2019 16(1):29-35 Background: Periodontitis is a public health concern since it is a major factor in tooth loss worldwide and has association with many systemic diseases. Sleep is a complex and essentially biological process and a critical factor for maintaining mental and physical health. Since inflammation is characteristic of both chronic periodontitis and sleep deprivation, few studies in recent years present the contradictory results regarding this potential association. The objective of the present study was to investigate the association between quality of sleep and chronic periodontitis. Materials and Methods: A total of 200 individuals participated in this study. All participants underwent a comprehensive clinical periodontal examination. Case–control were identified using the Centers for Disease Control and Prevention/American Academy of Periodontology case definitions for periodontal disease. The quality of sleep was assessed by Pittsburgh Sleep Quality Index. The univariate and multivariate logistic regression analysis was used to test the influence of variables (quality of sleep, age, sex, ethnicity, education, and socioeconomic status), in the occurrence of periodontitis. Odds ratio (OR) and respective confidence intervals (CIs) were calculated and reported. P ≤0.05 was considered statistically significant. Results: The prevalence of poor quality of sleep was 56.75% in cases (periodontitis group) and 43.24% in control group. There was positive association between quality of sleep and chronic periodontitis (OR = 3.04; 95% CI = 1.42–6.5; P = 0.004). In multivariate logistic regression analysis, only the age was significantly related to the periodontitis (OR = 1.11; 95% CI = 1.07–1.41; P < 0.001), other variables failed to reach the significant level. Conclusion: Poor quality of sleep was significantly associated with chronic periodontitis. Only the age was significantly related to periodontitis among the other covariable measured.

Sealants revisited: An efficacy battle between the two major types of sealants – A randomized controlled clinical trial B Prathibha, P Parthasarthi Reddy, Md Shakeel Anjum, M Monica, BH Praveen Dental Research Journal 2019 16(1):36-41 Background: The aim of this study is comparing the retention and caries preventive effect of the glass-ionomer fissure sealant and resin-based fissure sealant. Materials and Methods: A randomized-controlled split-mouth study was conducted to compare the retention and the caries preventive effect of light-cured resin-based sealant (3M ESPE) and glass ionomer sealant (Fuji VII). The sealants were applied to either the right or the left lower mandibular molars (7-9 yrs of age) in 120 school children, based on the randomization process. They were recalled for assessment of clinical retention at intervals of 3, 6, and 12 months. The caries-preventive effect between the two materials was tested statistically by the McNemar's test for matched pairs, and the differences observed with regard to the retention of the materials was tested by Chi-square tests. The level of significance was set to be at P < 0.05. Results: At the end of 12th month, sealant retention is found to be higher in the resin-based sealant group compared to the glass ionomer group. In the glass ionomer sealants placed, 101 (91%) were caries-free and 10 (9%) had caries. In the resin-based sealant, 105 (94.60%) had sound teeth and 6 (5.4%) had dental caries (P = 0.34). Conclusion: The glass ionomer sealant was less retentive when compared to resin sealants. The caries incidence between the glass ionomer and resin-based sealants was not statistically significant.

A comparative study of the clinical efficiency of chemomechanical caries removal using Carie-Care gel for permanent teeth of children of age group of 12–15 years with that of conventional drilling method: A randomized controlled trial Priyanka Sontakke, Prateek Jain, Aniket Dhote Patil, Gautam Biswas, Pramod Yadav, Diljot Kaur Makkar, Vikas Jeph, Banu Pyari Sakina Dental Research Journal 2019 16(1):42-46 Background: Dental caries is considered as one of the most serious dental diseases that results in localized dissolution and destruction of the calcified tooth tissues. As possible alternatives to conventional techniques of caries removal, chemomechanical caries removal systems have emerged. This study aims to clinically observe the advantages of chemomechanical method of caries removal over conventional technique. Materials and Methods: Inthis randomized controlled trial a total of 60 children with Class 1 open carious lesions were selected for the study. They were divided into two equal groups according to a method of caries removal (30 chemomechanical and 30 conventional on permanent molars). In Group A, caries was removed using the Carie-Care system and in Group B with the conventional drill and were restored equally with glass ionomer cement. The visual analogy face scale was used to determine the level of anxiety in children at baseline, during treatment and after treatment. Results: The results were subjected to statistical analysis using Student's unpaired t-test. It showed that though chemomechanical technique took a marginal increase in time compared to the conventional technique, it was found to be more comfortable for all the children. Conclusion: Chemomechanical technique though time-consuming is definitely superior compared to the conventional technique provided we use a less technique sensitive restorative material which retains in the oral cavity for longer period. It is definitely a better treatment protocol in school-based dental treatment and atraumatic restorative dentistry compared to the conventional technique.

The effect of office bleaching on the color and bond strength of resin restorations Homayoon Alaghehmand, Marzieh Rohaninasab, Ali Bijani Dental Research Journal 2019 16(1):47-52 Background: Bleaching may affect the bond strength of existing composite fillings and may weaken it. Hence, the aim of this study was to find the best method of in-office bleaching with the least effect on microshear bond strength (MSBS) of existing composite resin fillings to tooth structure. Materials and Methods: In this in vitro study, Class V cavities were prepared on buccal surface of 50 extracted third human sound molars. The cavities in 25 teeth had enamel axial walls, Group E, which were divided into five subgroups of E1 through E5 and in 25 teeth had dentin axial walls, Group D, which were divided into five subgroups of D1 through D5. Cavities were treated with Single Bond 2 adhesive system and restored with composite resin (Z250). The corresponding subgroups received similar bleaching methods and materials; 1 – not bleached, 2 – hydrogen peroxide (HP) 25%, 3 – HP + ultraviolet light, 4 – HP + light-emitting diode-curing device, and 5 – HP + diode laser. Teeth colors were monitored before and after bleaching, and MSBS test and failure modes were examined. Results were analyzed with one-way ANOVA and Kruskal–Wallis tests. P < 0.05 was considered significant. Results: One-way ANOVA did not show differences in MSBS of enamel subgroups but showed significant differences in dentin subgroups (P < 0.00). Adhesive fracture in all of the subgroups was the most frequent mode of failure. Kruskal–Wallis test showed that laser was the most effective instrument to change ΔE. Conclusion: Diode laser was the best method for tooth bleaching because lowering the shear bond strength between composite resin and enamel was minimum and also had the most ΔE in tooth bleaching.

In vitro evaluation of coronal discoloration following the application of calcium-enriched mixture cement, Biodentine, and mineral trioxide aggregate in endodontically treated teeth Solmaz Araghi, Atefeh Khavid, Mostafa Godiny, Mahshid Saeidipour Dental Research Journal 2019 16(1):53-59 Background: This study sought to assess and compare coronal discoloration following the application of white mineral trioxide aggregate, Biodentine, and calcium-enriched mixture cement in endodontically treated teeth. Materials and Methods: In this in vitro experimental study, 64 freshly extracted sound human premolars were selected, cleaned, and stored in saline. After cleaning, shaping, and obturation the root canal of the teeth, the teeth were randomly assigned to one control (n = 4) and three experimental (n = 20) groups. In the experimental groups, the cement were applied over the canal orifices in 3-mm thickness. All teeth were then restored with composite resin. Color parameters, according to the CIE L*a*b* system, were measured using Vita Easyshade spectrophotometer before application of cement and at 1 week, 1 month, 2 months, and 3 months after the application of cement. The recorded values were statistically analyzed using descriptive and analytical statistics. For analytical statistics, Kolmogorov–Smirnov test was applied to assess normal distribution of data. ANOVA was used to compare the results at baseline and repeated measures. P < 0.05 was considered statistically significant Results: Significant differences were noted in color change (ΔE) between all time points except between ΔE4 (2 months) and ΔE5 (3 months) (P < 0.01). However, tooth discoloration caused by the three cement was not significantly different (P = 0.343). Conclusion: The three tested cement were not significantly different in terms of causing coronal discoloration in endodontically treated teeth.

Stage I non-Hodgkin lymphoma: no plateau in disease-specific survival ?

Abstract

Stage I non-Hodgkin lymphoma (NHL) is rare; prognostic impact of different histologic subtypes and treatment modality is still unclear. We used the Surveillance, Epidemiology and End Results (SEER) database to evaluate survival outcomes among adult patients (age ≥ 18 years, N = 58,230) diagnosed with stage I NHL of various histologic subtypes between 1998 and 2014. Five-year disease-specific survival of patients with stage I diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), Burkitt lymphoma (BL), mantle cell lymphoma (MCL), and peripheral T cell lymphoma (PTCL) was 82%, 92%, 95%, 89%, 78%, 77%, and 77%, respectively. The median disease-specific survival was not reached in all histologic subtypes analyzed; however, there does not appear to be a plateau in disease-specific survival of patients with stage I NHL irrespective of subtypes. Although lymphoma was the most common cause of death (40.7%), death from other cancer (17.4%) and cardiovascular disease (13.6%) were also frequent. Chemotherapy appeared favorably associated with OS in patients with DLBCL, BL, and MCL while patients with FL, MZL, SLL, and PTCL who require chemotherapy for initial treatment showed shorter OS. Patients with stage I NHL have favorable disease-specific survival; however, no plateau was seen regardless of histologic subtypes thus suggesting that patients may need attention and follow-up even in aggressive lymphomas after 5 years of remission.

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Award-Winning Research— IAO 2018

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A Comparative Study between Universal Eclectic Septoplasty and Cottle

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Probable Association of Hearing Loss, Hypertension and Diabetes Mellitus in the Elderly

Abstract Introduction The aging process causes changes in body structure in a continuous manner, and contributes to clinical disorders. Life expectancy is increasing, especially in developing countries. Objective To assess the prevalence of hearing loss and its possible association with hypertension and diabetes mellitus (DM) in the elderly. Methods A cross-sectional study with 519 elderly individuals aged over 60 years who underwent an audiological evaluation (pure tone audiometry), and answered a comorbidity questionnaire that included questions about age, gender, tinnitus and medical history, with data concerning DM. The dependent variable was the presence of hearing loss. The independent variables were age, gender, DM and hypertension. The variables were presented in absolute numbers and proportions, and enabled us to estimate the prevalence. The statistical analysis was performed through multiple logistic regression with 95% confidence intervals and values of p< 0.05 for the hearing loss and its associated factors. Results A total of 519 subjects of both genders with a median age of 69 years were evaluated, and the individuals who did not attend the audiometric test were excluded from the study, so the final sample was composed of 498 subjects. Sensorineural hearing loss was more prevalent (66.26%) of most frequently with bilateral hearing loss of 91.56% and 26.50% with mild degree. The statistical analysis showed that the variable DM was associated with the high frequency of hearing loss in the elderly, and according to the multiple logistic regression, the risk factors are independent of the hearing loss only for age and exposure to occupational noise. Conclusions There was a statistically significant difference between hearing loss at high frequencies and the risk factors, that is, age and DM.

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Outcomes of Automated Auditory Evoked Potential Performed in Different Settings and the Factors Associated with Referred Cases

Abstract Introduction For the population with risk factors for hearing loss, the first option to assess the hearing status is the performance of the automated brainstem auditory evoked potential (BAEP) test because of its efficacy in identifying retrocochlear hearing loss. Objective To verify the outcomes of automated BAEP performed in different settings as well as the factors associated with the prevalence of hearing impairment. Methods Cross-sectional study conducted from October of 2014 to May of 2015. The sample consisted of 161 infants with at least one risk factor for hearing loss who underwent automated BAEP during the hospital stay or at the outpatient clinic. After 30 days, the altered cases were referred for BAEP diagnosis. Results One hundred and thirty-eight infants (86%) had a result of "pass" and 23 (14%) of "failure" in the automated BAEP. There was no statistically significant difference in the rate of "referred" results between examinations performed in different settings. The infants' ages did not influence the number of abnormal cases. All of the 23 infants who presented a "referred" result in the automated BAEP, unilateral or bilateral, were sent for BAEP diagnosis, and out of these, 9 (39%) remained with at least some degree of alteration. The average age of diagnosis was 2.7 months. Conclusion The results of the automated BAEP were similar when performed during hospitalization or after discharge. Neither the age at the examination nor the gender of the patient influenced the prevalence of hearing loss.

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The Contribution of Surface Electromyographic Assessment for Defining the Stage of Peripheral Facial Paralysis: Flaccid or Sequelae Stage

Abstract Introduction Surface electromyographic activity may not be symmetric, even in subjects with no facial paralysis history. Objective To evaluate the contribution of the index of electromyographic (IEMG) activity in the identification of the two extremes of the facial paralysis course. Methods Thirty-four subjects with unilateral peripheral facial paralysis were selected. A control group was composed of volunteers without a history of facial paralysis. The electromyographic assessment of the facial muscle was performed by placing surface electrodes during movements of the forehead, eyes and lips using MIOTEC equipment, such as the MIOTOOL (Miotec, Porto Alegre, Brazil) software. The electromyographic activity was also recorded in other channels during the primary activity to identify the presence of synkinesis. The statistical analysis was performed using the Statistical Package for Social Sciences for Macintosh (SPSS Inc, Chicago, IL, USA). The IEMG activity was obtained from the division of the electromyographic activity root mean square (RMS) values on both sides. Results There was a statistically significant difference among the groups in all the analyzed indexes. The ocular-oral synkinesis in all patients must be correctly identified (with 100% sensitivity and specificity) using an IEMG activity of 1.62 as a cutoff point. The oral-ocular synkinesis must be correctly identified (93.3% sensitivity and 95.9% specificity) using the IEMG activity of 1.79 as a cutoff point. Conclusion The IEMG activity is below the normal scores in patients in the flaccid stage, whereas patients in the sequelae stage can either show normal values or values above or below the normal scores. The IEMG activity was shown to have high sensitivity and specificity in the identification of synkinesis.

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Headphone Evaluation for App-Based Automated Mobile Hearing Screening

Abstract Introduction With the need for hearing screenings increasing across multiple populations, a need for automated options has been identified. This research seeks to evaluate the hardware requirements for automated hearing screenings using a mobile application. Objective Evaluation of headphone hardware for use with an app-based mobile screening application. Methods For the purposes of this study, hEAR, a Bekesy-based mobile application designed by the research team, was compared with pure tone audiometric tests administered by an audiologist. Both hEAR and the audiologist's test used 7 frequencies (125 Hz, 250 Hz, 500 Hz, 1,000 Hz, 2000 Hz, 4,000 Hz and 8,000 Hz) adopting four different sets of commercially available headphones. The frequencies were regarded as the independent variable, whereas the sound pressure level (in decibels) was the dependent variable. Thirty participants from a university in Texas were recruited and randomly assigned to one of two groups, whose only difference was the order in which the tests were performed. Data were analyzed using a generalized estimating equation model at α = 0.05. Results Findings showed that, when used to collect data with the mobile app, both the Pioneer HDJ-2000 (Pioneer, Bunkyo, Tokyo, Japan) (p> 0.05) and the Sennheiser HD280 Pro (Sennheiser, Wedemark, Hanover, Germany) (p> 0.05) headphones presented results that were not statistically different from the audiologist's data across all test frequencies. Analyses indicated that both headphones had decreased detection probability at 4kHz and 8kHz, but the differences were not statistically significant. Conclusion Data indicate that a mobile application, when paired with appropriate headphones, is capable of reproducing audiologist-quality data.

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Effect of Blood Group on Ultrahigh Frequency Auditory Sensitivity

Abstract Introduction Individuals with blood group O are reported to have reduced otoacoustic emissions (OAEs) compared with individuals with different blood groups. Objective The present study attempted to determine if the blood group has any effect on high-frequency auditory sensitivity using ultrahigh-frequency audiometry and ultrahigh-frequency distortion product otoacoustic emissions (DPOAEs). Methods High-frequency thresholds and high-frequency DPOAEs were measured in 60 individuals with normal hearing and different blood groups. Results The results of the study showed that there was a significant reduction in DPOAE amplitude for individuals with blood group O compared with individuals with other blood groups. However, there was no significant difference in ultrahigh-frequency thresholds across the blood groups. Conclusion This reduction in OAE amplitude may be attributed to a lower number of healthy outer hair cells in individuals with blood group O. Further studies on larger groups of individuals are essential for a better generalization of the results.

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A Comparison of the Operative Techniques and the Postoperative Complications for Bone-Anchored Hearing Aid Implantation

Abstract Introduction Bone anchored hearing aids (BAHA) represent a useful surgical option for patients with single sided deafness. Objectives To compare multiple techniques for BAHA implantation regarding postoperative complications, operative time, and duration between the surgery and the first use of the BAHA. Methods A retrospective study was conducted of all patients receiving implantation of a BAHA from August of 2008 to October of 2014. Data collected included: patient age, gender, side operated, abutment length, operative time, duration until first use of the BAHA, operative technique, and postoperative complications. The statistical analysis was performed using analysis of variance (ANOVA), Tukey pairwise comparison, chi-square, and paired t-test. Statistical significance was determined using a level of p< 0.05. Results A total of 88 patients (43 female and 45 male) were included in the data analysis. A total of 80 complications were documented, and these complications were classified according to the Holgers criteria. A significant difference in the total postoperative complications existed between the six techniques used (ANOVA; p< 0.01). In addition, there was also a significant difference among the six techniques employed regarding the operative time (ANOVA; p< 0.01). The average time duration until fitting of the BAHA processor among the various techniques trended toward but did not reach statistical significance (ANOVA; p= 0.16). Conclusions Significant differences in the operative outcomes exist among the various techniques for BAHA implantation. Based on the statistical analysis of our data, the BAHA Attract system (Cochlear Ltd., Sidney, Australia) requires greater operative time, but it is associated with less postoperative complications than percutaneous techniques and its processor may be fitted significantly sooner.

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Effect of HIV and Antiretroviral Treatment on Auditory Functions

Abstract Introduction Numerous studies have evaluated auditory functions in human immunodeficiency virus (HIV) patients; however, these studies had a few major limitations in terms of methodology as they used mainly evoked audiometry although this method is expensive, time consuming and not widely available. Therefore, we conducted a study in naïve HIV subjects with routine audiometry. Objective To determine the effect of HIV and of the drugs used to treat it on the auditory functions. Methods A prospective observational study was conducted in a medical college with 25 naive HIV-seropositive patients for over a year. Pure tone audiometry (250–8,000 Hz) and CD4 T-lymphocyte count were performed at the time of enrollment and 6 months after commencement of highly active antiretroviral treatment. Results The subjects had increased hearing thresholds at high frequencies (4 KHz and 8KHz) in both ears at the time of enrollment that persisted at the same level (p > 0.05) on follow-up at 6 months. None of the subjects had any other otological symptom during the 6 months of observation. Seven subjects had sensorineural hearing loss in one or both ears at 0 and 6 months. These observations did not show any significant difference on Wilcoxon-signed-rank test. Spearman correlation did not find a significant correlation (p > 0.05) between CD4 T-lymphocyte counts and pure tone audiometry during the study. Conclusion We found high-frequency hearing loss in all subjects with no relation with highly active antiretroviral therapy (HAART) and severity of the disease. This study advocates hearing assessment with pure tone audiometry in HIV subjects so that intervention can be initiated in a timely manner.

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Effect of Fractal Tones on the Improvement of Tinnitus Handicap Inventory Functional Scores among Chronic Tinnitus Patients: An Open-label Pilot Study

Abstract Introduction Music-based sound therapies become recently a trend in the treatment of tinnitus. Few publications have studied the therapeutic use of fractal tones to treat chronic tinnitus. Objective The aim of this study was to determine the benefits of using fractal tones as a unique sound therapy for chronic tinnitus sufferers. Methods Twelve participants were recruited; however, six could not be assigned. At baseline and at 1, 3 and 6 months, the participants were provided with the Tinnitus Handicap Inventory (THI) and Hearing Handicap Inventory for Adults (HHIA) questionnaires, and their visual analog scale score was recorded. Tinnitus pitch and loudness matching was performed before fitting and after 6 months of use. Results The visual analog scale (VAS) score, pitch and loudness matching and minimal masking levels did not result in significant improvement at the end of the treatment. The mean THI measured at baseline was 45, and the final one was 25. A paired sample t-test showed that this 20-point difference was statistically significant. Conclusions We measured the benefits of using fractal tone therapy for the treatment of chronic tinnitus and found that most of the benefits were in the THI functional domain, which includes concentration, reading, attention, consciousness, sleep, social activities, and household tasks. For all patients with bothersome chronic tinnitus and high scores on the THI functional scale, fractal tones should be considered a promising initial sound therapy strategy. The findings from this open-label pilot study are preliminary, and further trials are needed before these results can be generalized to a larger tinnitus population.

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Determination of Factors Associated with Critical Weight Loss in Oral Cavity Carcinoma Patients: A Retrospective Cohort Study

Abstract Introduction Critical weight loss is defined as an unintentional weight loss of ≥ 5% at 1 month or ≥ 10% at 6 months from the start of treatment. Critical weight loss leads to deterioration of the immune function and reduced tolerance to treatment (surgery ± radiochemotherapy) as well as increased complication rates. Objective Critical weight loss, defined as a weight loss of ≥ 5% after 1 month or ≥ 10% after 6 months from the start of treatment, is not uncommon in head and neck cancer patients. We aimed to assess the factors associated with critical weight loss during the treatment of oral cavity squamous cell carcinoma patients. Methods A retrospective cohort study was performed at the Aga Khan University Hospital, in Karachi, Pakistan, on 125 patients. Patients receiving adjuvant therapy were considered exposed, and the outcome was critical weight loss. Results The mean age of presentation was 46.9 ± 12.8 years in patients undergoing surgery and adjuvant therapy, with 119 (79.3%) of them being male and 31 (20.7%) female. One hundred and twelve patients (81.3%) developed critical weight loss at 6 months from the start of treatment, and the only significant variable associated with critical weight loss was the stage of the disease (p= 0.03). Conclusion A large proportion of patients with oral cancer developed critical weight loss requiring a need for intervention. The overall stage of the disease is a significant predictor of critical weight loss in patients undergoing treatment.

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Identification of Fungal Pathogens in Otomycosis and Their Drug Sensitivity: Our Experience

Abstract Introduction Otomycosis is a common problem in otolaryngology practice. However, we usually encounter some difficulties in its treatment because many patients show resistance to antifungal agents, and present high recurrence rate. Objectives To determine the fungal pathogens that cause otomycosis as well as their susceptibility to the commonly used antifungal agents. Additionally, to discover the main reasons for antifungal resistance. Methods We conducted an experimental descriptive study on 122 patients clinically diagnosed with otomycosis from April 2016 to April 2017. Aural discharge specimens were collected for direct microscopic examination and fungal culture. In vitro antifungal susceptibility testing was performed against the commonly used antifungal drugs. We tested the isolated fungi for their enzymatic activity. Results Positive fungal infection was found in 102 samples. The most common fungal pathogens were Aspergillus and Candida species, with Aspergillus niger being the predominant isolate (51%). The antifungal susceptibility testing showed that mold isolates had the highest sensitivity to voriconazole (93.48%), while the highest resistance was to fluconazole (100%). For yeast, the highest sensitivity was to nystatin (88.24%), followed by amphotericin B (82.35%), and the highest resistance was to terbinafine (100%), followed by Itraconazole (94.12%). Filamentous fungi expressed a high enzymatic ability, making them more virulent. Conclusion The Aspergillus and Candida species are the most common fungal isolates in otomycosis. Voriconazole and Nystatin are the medications of choice for the treatment of otomycosis in our community. The high virulence of fungal pathogens is owed to their high enzymatic activity. Empirical use of antifungals should be discouraged.

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Do Otolaryngology Patients Show Gender Preference When Choosing a Surgeon? — A Quantitative and Qualitative Analysis

Abstract Introduction Otorhinolaryngology has always been considered a gender-neutral specialty, whereas in several other specialties, such as obstetrics, gynecology and urology, gender preference has been consistently shown by patients when choosing their treating surgeon. To date, no study has been performed to analyze whether this practice of gender preference is prevalent in otorhinolaryngology patients too. Objectives To identify if gender preference exists in the field of otorhinolaryngology, specifically in its four subspecialties, namely otology, pediatric otolaryngology, laryngology and head and neck surgery. Methods Patients attending our outpatient department were asked to complete a preformed proforma. The pro forma consisted of two parts, demographic details of the subjects and gender preference in the following subspecialties: otology, pediatric otolaryngology, laryngology and head and neck oncosurgery. Results A total of 1,112 subjects took part in the study, out of which 1,089 subjects were included in the final analysis. Female gender preference was highest in the field of pediatric otolaryngology, while male preference was highest for head and neck oncosurgery. Conclusion Though otorhinolaryngology and head and neck surgery has been considered a gender-neutral field, subspecialties of this field show considerable gender preference.

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P3 Cognitive Potential in Cochlear Implant Users

Abstract Introduction The P3 cognitive evoked potential is recorded when a subject correctly identifies, evaluates and processes two different auditory stimuli. Objective to evaluate the latency and amplitude of the P3 evoked potential in 26 cochlear implant users with post-lingual deafness with good or poor speech recognition scores as compared with normal hearing subjects matched for age and educational level. Methods In this prospective cohort study, auditory cortical responses were recorded from 26 post-lingual deaf adult cochlear implant users (19 with good and 7 with poor speech recognition scores) and 26 control subjects. Results There was a significant difference in the P3 latency between cochlear implant users with poor speech recognition scores (G-) and their control group (CG) (p= 0.04), and between G- and cochlear implant users with good speech discrimination (G+) (p= 0.01). We found no significant difference in the P3 latency between the CG and G+. In this study, all G- patients had deafness due to meningitis, which suggests that higher auditory function was impaired too. Conclusion Post-lingual deaf adult cochlear implant users in the G- group had prolonged P3 latencies as compared with the CG and the cochlear implant users in the G+ group. The amplitudes were similar between patients and controls. All G- subjects were deaf due to meningitis. These findings suggest that meningitis may have deleterious effects not only on the peripheral auditory system but on the central auditory processing as well.

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Benefit of Cochlear Implantation in Children with Multiple-handicaps: Parent's Perspective

Abstract Introduction The cochlear implants centers in the world are studying the cochlear implantation in children with multiple handicaps. Objective To develop a questionnaire to analyze the subjective benefits of the cochlear implantation in multiple handicapped children according to their parent's perspective. Methods A questionnaire was applied to 14 families of multiple handicapped children, aging from 2–12 years old and having from 11 months to 11 years of implant use. Results The social-emotional abilities were improved because of many factors, such as: auditory exposure, which happened in 84% of the children; recognition of their own names, which increased in 56%; and development of eye contact, in 28% of the subjects. Other benefits appeared to be: music appreciation and more attention and adherence to other therapies and school activities. Besides, some children became interested in objects, playing with other children, and more adapted to daily routines. Thirty-five percent of the children acquired oral language, mainly the bilaterally implanted, while 14% of them were engaged in sign language. Although all of the children showed a significant improvement in communication, the emotional issues of some families and the severity of the handicaps negatively impacted the outcomes. In spite of the families' acknowledgement of some benefits, the diagnosis of autism spectrum disorder caused frustration, requiring a readjustment of the expectations. Conclusion The questionnaire turned out to be an adequate tool to reveal the social-emotional benefits of cochlear implantation. Although oral language was not the major outcome in these cases, the cochlear implant benefits involved the whole family. All of the families recommended the implant to other children in a similar situation.

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Comparison of 1α-25-dihydroxyvitamin D3 and IgE Levels between Allergic Rhinitis Patients and Healthy People

Abstract Introduction Allergic rhinitis is one of the most common allergic diseases that cause a decrease in quality of life. Over the last decades, the increase in the number of cases is supposed to be a result of industrialization and lifestyle changes. Vitamin D, which is a steroid hormone, has a significant immunomodulatory and antioxidant role in the human body. Objective The objective of the present study is to investigate the role of 1α-25-dihydroxyvitamin D3 levels in allergic rhinitis patients and to compare them to the levels found in the healthy population. Methods A total of 256 participants were included in the present study. Allergic rhinitis is diagnosed with the help of the Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines confirmed through skin prick tests. Control subjects were selected among people without allergy history, which was also confirmed through skin prick tests. The levels of 1α-25-dihydroxyvitamin D3, immunoglobulin E (IgE), and eosinophil counts were measured in blood samples from both groups. Results The mean value of serum levels of 1α-25-hydroxyvitamin D3 was 25.5 ± 3.74 in the allergic rhinitis group, and 31.58 ± 3.85 in the control subjects. This difference reveals statistically-decreased levels in the allergic rhinitis group (p< 0.05). The total IgE levels are increased in the allergic rhinitis group (p< 0.05) and negatively correlated with the serum levels of 1α-25-hydroxyvitamin D3 (r = - 0.259, p< 0.05). Conclusion Lower serum levels of 1α-25-hydroxyvitamin D3 were detected in the allergic rhinitis population. This data is also correlated to the IgE response in the study group. A supplement of 1α-25-hydroxyvitamin D3 in deficient patients might be helpful to relieve symptoms and signs of allergic rhinitis, but further studies are needed.

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The Role of Modified Expansion Sphincter Pharyngoplasty in Multilevel Obstructive Sleep Apnea Syndrome Surgery

Abstract Introduction Obstructive sleep apnea syndrome (OSAS) is a sleep disorder caused by an excessive narrowing of the pharyngeal airway that also collapses during inspiration, with an important role played by the lateral pharyngeal wall in the development of the obstruction. Objective To describe our surgical experience with modified expansion sphincter pharyngoplasty (MESP) in the management of lateral collapse in upper airway multilevel surgery. Methods A total of 20 patients with moderate to severe OSAS were recruited in the Ear, Nose and Throat (ENT) Department of the University of Palermo, Italy. All of the enrolled patients refused the ventilatory therapy. The subjects were evaluated for snoring, and daytime sleepiness had a clinical evaluation including collection of anthropometric data and ENT examination and rhinofibroscopy with Müller maneuver. The patients undergoing upper airway multilevel surgery and we selected for MESP the patients with an oropharyngeal transverse pattern of collapse at Müller maneuver. Results In the postoperative assessment, all of the patients reported a reduction in snoring scores and daytime sleepiness. We observed a reduction in the mean apnea-hypopnea index (AHI) of 57.5% of the sample, which decreased from a mean value of 41.7 ( ± 21.5) to 17.4 ( ± 8.9) (p< 0.05), with a success rate, according to the Sher criteria, of 65%. We observed very few postoperative complications. Conclusion Modified expansion sphincter pharyngoplasty in multilevel surgical therapy preceded by a careful selection of patients has proven to be effective in treating patients with moderate to severe syndromes.

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Timing of Tracheostomy in Intensive Care Unit Patients

Abstract Introduction The ideal timing of tracheostomy in intensive care units (ICUs) for critically ill patients undergoing prolonged mechanical ventilation (MV) is still a controversial issue. Objectives To determine the proper timing of tracheostomy and its impact on various clinical outcomes of adult patients in ICUs undergoing prolonged MV. Methods The present study consisted of a sample of 67 ICU adult patients who were submitted to open surgical tracheostomy and divided into two groups: 30 patients in the early tracheostomy (ET) group (within 1–10 days post intubation), and 37 patients in the late tracheostomy (LT) group (within 11–21 days post intubation). The correlation between the timing of tracheostomy of each group and various associated ICU clinical parameters were analyzed. Results The sample consisted of 61.19% male and 38.81% female patients, with a mean age of 47.263 ± 7.581 years. The mean MV duration in days was 7.91 ± 4.937 standard deviation (SD) in the ET group, and 15.32 ± 7.472 SD in the LT group (p= 0.001), with a mean sedation time of 6.13 ± 4.647 SD in the ET group, and of 11.98 ± 6.596 SD in the LT group (p= 0.001). The duration of the weaning process duration had a mean of 2.75 ± 2.586 SD days in the ET group, and of 5.39 ± 5.817 SD days in the LT group (p= 0.025), with a weaning failure rate of 28.57% in the ET group and 71.42% in the LT group (p= 0.01). The Mean ICU stay was 26.18 ± 4.732 SD in the ET group, and 11.98 ± 6.596 SD in the LT group (p= 0.879), and the incidence of ventilator-associated pneumonia (VAP) of 23.33% in the ET group and of 27.02% in the LT group (p= 0.15). Conclusion Early tracheostomy had a notable benefit in shortening the duration of the MV, lessening the sedation time and minimizing the risks of weaning failure, but it had no significant impact on both the overall duration of ICU stay and VAP incidence.

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Hormone Replacement Therapy in Cancer Survivors – Review of the Literature

Abstract

Rapid advance in oncology leads to increasing survival of oncologic patients. More and more of them live long enough to reach either the natural age of menopause or, as a side effect of their oncotherapy, experience the cessation of gonadal function, leading to premature ovarian insufficiency, with disturbing vasomotor symtoms and long-term negative cardiovascular and skeletal effects. Thus, an ever increasing number of cancer survivors search endocrinologic help in the form of hormone replacement therapy (HRT). The misinterpretation of the WHI (Women's Health Initiative) Study has lead to an irrational fear of female hormone replacement, both by the general population and medical professionals. It has seemed the logical and safe conclusion to many physicians to avoid HRT, supposing that this attitude definitely causes no harm, whereas the decision of prescribing estrogen alone or with progestins might bear oncologic and thromboembolic risks and may even lead to litigation in case of a potentially related complication. However, it was known even before the WHI results that premature menopause and hypogonadism decreases the life expectancy of women by years through its skeletal and cardiovascular effects, and this negative effect correlates with the length of the hypoestrogenaemic period. Therefore, the denial of HRT also needs to be supported by evidence and should be weighed againts the risks of HRT. Yet, the oncologic risk of HRT is extremely difficult to assess. In this work we review the latest evidence from in vitro experiments to clinical studies, regarding HRT in survivors of gynecologic and non-gynecologic cancers. Based on our literature research, we group tumours regarding the oncologic risk of properly chosen female hormone replacement therapy in cancer survivors as follows: 'HRT is advanageous' (e.g. endometrial cancer type I, cervical adenocarcinoma, haematologic malignancies, local cutaneous malignant melanoma, colorectal cancer, hepatocellular cancer); 'HRT is neutral' (e.g. BRCA 1/2 mutation carriers without cancer, endometrial cancer type II, uterinal carcinosarcoma and adenosarcoma, certain types of ovarian cancer, cervical, vaginal and vulvar squamous cell carcinoma, prolactinoma, kidney cancer, pancreatic cancer, thyroid cancer); 'HRT is relatively contraindicated' for various reasons (e.g. leiomyosarcoma, certain types of ovarian tumours, brain tumours, advanced metastatic malignant melanoma, lung cancer, gastric cancer, bladder cancer); 'HRT is diasadvantageous and thus contraindicated' (e.g. breast cancer, endometrial stroma sarcoma, meningioma, glioma, hormone receptor positive gastric and bladder cancer).

http://bit.ly/2Tya3N1

Risk factors for respiratory failure in Guillain‐Barré syndrome in Bangladesh: a prospective study

Abstract

Objective

We investigated clinical, biological, and electrophysiological risk factors for mechanical ventilation (MV) and patient outcomes in Bangladesh using one of the largest, prospective Guillain‐Barré syndrome (GBS) cohorts in developing world.

Methods

A total of 693 GBS patients were included in two GBS studies conducted between 2006 and 2016 in Dhaka, Bangladesh. Associations between baseline characteristics and MV were tested using Fisher's exact test, χ² test, or Mann–Whitney U‐test, as appropriate. Risk factors for MV were assessed using multivariate logistic regression. Survival analysis was performed using Kaplan–Meier method; comparisons between groups performed using log‐rank test.

Results

Of 693 patients, 155 (23%) required MV (median age, 26 years; interquartile range [IQR] 17–40). Among the ventilated patients, males were predominant (68%) than females. The most significant risk factor for MV was bulbar involvement (adjusted odds ratio [AOR]:19.07; 95% CI = 89.00–192.57, P = 0.012). Other independently associated factors included dysautonomia (AOR:4.88; 95% CI = 1.49–15.98, P = 0.009) and severe muscle weakness at study entry (AOR:6.12; 95% CI = 0.64–58.57, P = 0.048). At 6 months after disease onset, 20% of ventilated and 52% of non‐ventilated patients (P < 0.001) had recovered completely or with minor symptoms. Mortality rate was significantly higher among ventilated patients than non‐ventilated patients (41% vs. 7%, P < 0.001).

Interpretation

Bulbar involvement, dysautonomia and severe muscle weakness were identified as the most important risk factors for MV among GBS patients from Bangladesh. The findings may help to develop predictive models for MV in GBS in developing countries to identify impending respiratory failure and proper clinical management of GBS patients.

http://bit.ly/2LVpxIm

Obligatory role of endoplasmic reticulum in brain FDG uptake

Abstract

Purpose

The endoplasmic reticulum (ER) contains hexose-6P-dehydrogenase (H6PD). This enzyme competes with glucose-6P-phosphatase for processing a variety of phosphorylated hexoses including 2DG-6P. The present study aimed to verify whether this ER glucose-processing machinery contributes to brain FDG uptake.

Methods

Effect of the H6PD inhibitor metformin on brain 18F-FDG accumulation was studied, in vivo, by microPET imaging. These data were complemented with the in vitro estimation of the lumped constant (LC). Finally, reticular accumulation of the fluorescent 2DG analogue 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose (2NBDG) and its response to metformin was studied by confocal microscopy in cultured neurons and astrocytes.

Results

Metformin halved brain 18F-FDG accumulation without altering whole body tracer clearance. Ex vivo, this same response faced the doubling of both glucose consumption and lactate release. The consequent fall in LC was not explained by any change in expression or activity of its theoretical determinants (GLUTs, hexokinases, glucose-6P-phosphatase), while it agreed with the drug-induced inhibition of H6PD function. In vitro, 2NBDG accumulation selectively involved the ER lumen and correlated with H6PD activity being higher in neurons than in astrocytes, despite a lower glucose consumption.

Conclusions

The activity of the reticular enzyme H6PD profoundly contributes to brain 18F-FDG uptake. These data challenge the current dogma linking 2DG/FDG uptake to the glycolytic rate and introduce a new model to explain the link between 18-FDG uptake and neuronal activity.

http://bit.ly/2CWpo4q

Cancers, Vol. 11, Pages 50: Dynamic Thromboembolic Risk Modelling to Target Appropriate Preventative Strategies for Patients with Non-Small Cell Lung Cancer

Cancers, Vol. 11, Pages 50: Dynamic Thromboembolic Risk Modelling to Target Appropriate Preventative Strategies for Patients with Non-Small Cell Lung Cancer

Cancers doi: 10.3390/cancers11010050

Authors: Marliese Alexander David Ball Benjamin Solomon Michael MacManus Renee Manser Bernhard Riedel David Westerman Sue M. Evans Rory Wolfe Kate Burbury

Prevention of cancer-associated thromboembolism (TE) remains a significant clinical challenge and priority world-wide safety initiative. In this prospective non-small cell lung cancer (NSCLC) cohort, longitudinal TE risk profiling (clinical and biomarker) was undertaken to develop risk stratification models for targeted TE prevention. These were compared with published models from Khorana, CATS, PROTECHT, CONKO, and CATS/MICA. The NSCLC cohort of 129 patients, median follow-up 22.0 months (range 5.6&mdash;31.3), demonstrated a hypercoagulable profile in &gt;75% patients and TE incidence of 19%. High TE risk patients were those receiving chemotherapy with baseline fibrinogen &ge; 4 g/L and d-dimer &ge; 0.5 mg/L; or baseline d-dimer &ge; 1.5 mg/L; or month 1 d-dimer &ge; 1.5 mg/L. The model predicted TE with 100% sensitivity and 34% specificity (c-index 0.67), with TE incidence 27% vs. 0% for high vs. low-risk. A comparison using the Khorana, PROTECHT, and CONKO methods were not discriminatory; TE incidence 17&ndash;25% vs. 14&ndash;19% for high vs. low-risk (c-index 0.51&ndash;0.59). Continuous d-dimer (CATS/MICA model) was also not predictive of TE. Independent of tumour stage, high TE risk was associated with cancer progression (HR 1.9, p = 0.01) and mortality (HR 2.2, p = 0.02). The model was tested for scalability in a prospective gastrointestinal cancer cohort with equipotency demonstrated; 80% sensitivity and 39% specificity. This proposed TE risk prediction model is simple, practical, potent and can be used in the clinic for real-time, decision-making for targeted thromboprophylaxis. Validation in a multicentre randomised interventional study is underway (ACTRN12618000811202).

http://bit.ly/2C7t8ON

High Level of Conservation of Mitochondrial RNA Editing Sites Among Four Populus Species

RNA editing occurs in the endosymbiont organelles of higher plants as C-to-U conversions of defined nucleotides. The availability of large quantities of RNA sequencing data makes it possible to identify RNA editing sites and to quantify their editing extent. We have investigated RNA editing in 34 protein-coding mitochondrial transcripts of four Populus species, a genus noteworthy for its remarkably small number of RNA editing sites compared to other angiosperms. 27 of these transcripts were subject to RNA editing in at least one species. In total, 355 RNA editing sites were identified with high confidence, their editing extents ranging from 10 to 100%. The most heavily edited transcripts were ccmC with the highest density of RNA editing sites (50.5 sites / kb) and ccmFn with the highest number of sites (39 sites). Most of the editing events are at position 1 or 2 of the codons, usually altering the encoded amino acid, and are highly conserved among the species, also with regard to their editing extent. However, one SNP was found in the newly sequenced and annotated mitochondrial genome of P. alba resulting in the loss of an RNA editing site compared to P. tremula and P. davidiana. This SNP causes a C-to-T transition and an amino acid exchange from Ser to Phe, highlighting the widely discussed role of RNA editing in compensating mutations.

http://bit.ly/2TCtJzo

Investigation of novel pmrB and eptA mutations in isogenic Acinetobacter baumannii isolates associated with colistin resistance and increased virulence in vivo [Mechanisms of Resistance]

Colistin resistance in Acinetobacter baumannii is of great concern and a threat to human health. In this study we investigate the mechanisms of colistin resistance in four isogenic pairs of A. baumannii isolates displaying an increase in colistin MICs. A mutation in pmrB was detected in each colistin-resistant isolate, three of which were novel (A28V, I232T, L9-G12). Increased expression of pmrC was shown by qRT-PCR for three colistin-resistant isolates, and the addition of phosphoethanolamine (PEtN) to lipid A by PmrC was revealed by mass spectrometry. Interestingly, PEtN addition was also observed in some colistin-susceptible isolates, indicating that this resistance mechanism might be strain-specific and that other factors could contribute to colistin resistance. Furthermore, the introduction of pmrAB carrying the short amino acid deletion L9-G12 into a pmrAB knockout strain resulted in increased pmrC expression and lipid A modification, but colistin MICs remained unchanged, further supporting the strain-specificity of this colistin resistance mechanism. Of note, a mutation in the pmrC-homologue eptA and a point mutation in ISAba1 upstream of eptA were associated with colistin-resistance and increased eptA expression, which is a hitherto undescribed resistance mechanism. Moreover, no cost of fitness was observed for colistin-resistant isolates, while the virulence of these isolates was increased in a Galleria mellonella infection model. Although the mutations in pmrB were associated with colistin resistance, PEtN addition appears not to be the sole factor leading to colistin resistance, indicating that the mechanism of colistin resistance is far more complex than previously suspected and is potentially strain-specific.

http://bit.ly/2SD5xfT

Antimicrobial Activity of Omadacycline Tested against Clinical Bacterial Isolates from Hospitals in China (including Hong Kong) and Taiwan: Results from the SENTRY Antimicrobial Surveillance Program (2013-2016) [Epidemiology and Surveillance]

Omadacycline is a derivative of minocycline and the first agent of the aminomethylcycline class. A total of 3,282 organisms (one per patient) were consecutively collected from patients hospitalized in China (including Hong Kong) and Taiwan. Susceptibility testing was performed by broth microdilution methods in a central laboratory (JMI Laboratories). The collection included Gram-positive and Gram-negative organisms from patients with pneumonia, bloodstream, skin, community-acquired respiratory, and other infections. Omadacycline was very potent against Staphylococcus aureus (n=689; MIC_50/90, 0.12/0.25 mg/L), including methicillin-resistant isolates (MRSA; n=299; MIC_50/90, 0.12/0.5 mg/L), and had similar activity across geographic regions. Omadacycline was very active against Streptococcus pneumoniae (highest MIC, 0.25 mg/L), β-hemolytic streptococci (highest MIC, 1 mg/L), viridans group streptococci (highest MIC, 0.25 mg/L), and Enterococcus spp. (highest MIC, 0.5 mg/L) from all geographic regions. Overall, 53.8% of S. pneumoniae were penicillin-resistant (PRSPN; penicillin MIC, ≥2 mg/L) and 10.7% of enterococci (21.2% among E. faecium) were vancomycin-resistant (VRE). Omadacycline was active against Haemophilus influenzae (MIC_50/90, 0.5/1 mg/L) regardless of β-lactamase production and was active against Moraxella catarrhalis (MIC_50/90, ≤0.12/0.25 mg/L). Against Enterobacteriaceae, omadacycline was most active against Escherichia coli (MIC_50/90, 1/2 mg/L), Klebsiella oxytoca (MIC_50/90, 1/4 mg/L), and Enterobacter cloacae (MIC_50/90, 2/4 mg/L). Omadacycline showed potent in vitro activity against Gram-positive and Gram-negative pathogens isolated from China and Taiwan, and retained activity against problem pathogens, such as MRSA, VRE, PRSPN, and extended-spectrum β-lactamase-producing E. coli. The observed MIC profile in Chinese isolates was very similar to that seen in the US and European surveillance studies.

http://bit.ly/2SCtFj2

Adjuvant {beta}-lactam therapy combined with vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia: Does {beta}-lactam class matter? [Clinical Therapeutics]

We analyzed the impact of vancomycin (VAN) combined with adjuvant β-lactam therapy (COMBO) on persistent methicillin-resistant Staphylococcus aureus bacteremia (≥5 days) compared to VAN using pooled data from two previously published, observational studies (n=156). COMBO was inversely associated with persistent bacteremia (adjusted odds ratio 0.460, 95% confidence interval, 0.229-0.923). Acute kidney injury was more common in COMBO than VAN (18.9% and 7.6%, respectively; p=0.062).

http://bit.ly/2Ay0dDS

Effects of KPC variant and porin genotype on the in vitro activity of meropenem-vaborbactam against carbapenem-resistant Enterobacteriaceae [Mechanisms of Resistance]

Meropenem-vaborbactam is a new agent with potential to treat carbapenem-resistant Enterobacteriaceae (CRE) infections. We described the in vitro activity of meropenem-vaborbactam against representative CRE genotypes and laboratory engineered E. coli harboring mutant bla_KPC genes associated with ceftazidime-avibactam resistance. We also compared disk diffusion and gradient strip testing methods to standard broth microdilution methods. Against 120 CRE isolates, median ceftazidime-avibactam and meropenem-vaborbactam minimum inhibitory concentrations (MICs) were 1 and 0.03μg/mL, respectively. Ninety-eight percent (117/120) of isolates were susceptible to meropenem-vaborbactam (MIC ≤4μg/mL). Against K. pneumoniae harboring mutant bla_KPC, the addition of vaborbactam lowered meropenem MICs in 78% of isolates (14/18); 100% were susceptible to meropenem-vaborbactam. Median meropenem-vaborbactam MICs were higher against KPC-producing K. pneumoniae with mutant (n=26) versus wild-type (n=54) ompK36 porin genes (0.25 vs 0.03μg/mL; P<0.0001). Against E. coli TOP10 with plasmid constructs containing wild-type bla_KPC or mutant bla_KPC, the addition of vaborbactam 8μg/mL lowered meropenem MICs 2 – 512-fold, resulting in meropenem-vaborbactam MICs 0.03 μg/mL. Rates of categorical agreement with broth microdilution for disk diffusion or gradient strips ranged between 90 and 95%. Essential agreement rates were higher for gradient strips manufactured by bioMérieux (82%) compared to Liofilchem (48%; P<0.0001). Taken together, our data highlight the potent in vitro activity of meropenem-vaborbactam against CRE, including isolates resistant to ceftazidime-avibactam. Vaborbactam inhibited both wild-type and variant KPC enzymes. On the other hand, KPC-producing K. pneumoniae with ompK36 mutations displayed higher meropenem-vaborbactam MICs than isolates with wild-type ompK36. Susceptibility testing with bioMérieux gradient strips most closely aligned with broth microdilution methods.

http://bit.ly/2Au3oML