Accuracy and trending ability of the fourth-generation FloTrac/Vigileo System™ in patients undergoing abdominal aortic aneurysm surgery

Abstract

Purpose

The fourth-generation FloTrac/Vigileo™ improved its algorithm to follow changes in systemic vascular resistance index (SVRI). This revision may improve the accuracy and trending ability of CI even in patients who undergo abdominal aortic aneurysm (AAA) surgery which cause drastic change of SVRI by aortic clamping. The purpose of this study is to elucidate the accuracy and trending ability of the fourth-generation FloTrac/Vigileo™ in patients with AAA surgery by comparing the FloTrac/Vigileo™-derived CI (CI_FT) with that measured by three-dimensional echocardiography (CI_3D).

Methods

Twenty-six patients undergoing elective AAA surgery were included in this study. CI_FT and CI3_D were determined simultaneously in eight points including before and after aortic clamp. We used CI_3D as the reference method.

Results

In the Bland–Altman analysis, CI_FT had a wide limit of agreement with CI_3D showing a percentage error of 46.7%. Subgroup analysis showed that the percentage error between CO_3D and CO_FT was 56.3% in patients with cardiac index < 2.5 L/min/m² and 28.4% in patients with cardiac index ≥ 2.5 L/min/m². SVRI was significantly higher in patients with cardiac index < 2.5 L/min/m² (1703 ± 330 vs. 2757 ± 798; p < 0.001). The tracking ability of fourth generation of FloTrac/Vigileo™ after aortic clamp was not clinically acceptable (26.9%).

Conclusions

The degree of accuracy of the fourth-generation FloTrac/Vigileo™ in patients with AAA surgery was not acceptable. The tracking ability of the fourth-generation FloTrac/Vigileo™ after aortic clamp was below the acceptable limit.

https://ift.tt/2Gu2twG

Trends in the Implementation of Active Surveillance for Low-Risk Papillary Thyroid Microcarcinomas at Kuma Hospital: Gradual Increase and Heterogeneity in the Acceptance of This New Management Option

Thyroid, Ahead of Print.


https://ift.tt/2Gwd7mO

Quantitative Analysis of the Benefits and Risk of Thyroid Nodule Evaluation in Patients ≥70 Years Old

Thyroid, Ahead of Print.


https://ift.tt/2pZVV2J

Seasonal Changes in Serum TSH Concentrations Observed from Big Data Obtained During Six Consecutive Years from 2010 to 2015 at a Single Hospital in Japan

Thyroid, Ahead of Print.


https://ift.tt/2GwcTMu

“Hanger” in Intubation and Laryngoscopy

Abstract

Achieving an adequate exposure in laryngoscopy is an extremely tedious task for the operating surgeon, especially for the anterior commissure lesions. Various maneuvers have been described to overcome this difficulty, but failed in providing an adequate exposure leading to a poor outcome. To create a device that can deliver uniform pressure over the laryngeal cartilage and succeed in providing an adequate exposure of the glottic lesion. A total of 44 patients were included in the study, divided into two groups containing 22 patients each. The distance at the level of anterior commissure from the superior border of the distal end of the laryngoscope was noted and compared. Group A subjected to digital cricoid pressure showed a mean distance of 9.09 of exposure with variance of 1.22 and Group B subjected to cricoid pressure with the cricoid catapult showed a mean distance of 11.76 with variance of 1.59. The groups were statistically analyzed using Anova Test and the test was found to be very significant (p < 0.0001). The catapult is made of a hanger defining its economics, which has a vital role in difficult intubations especially in anterior placed larynx, short neck and obese patients, also succeeds in providing an adequate exposure of the glottic lesion, (especially the anterior commissure) by delivering uniform pressure over the laryngeal cartilage, leading to a superior operative outcome.

https://ift.tt/2JdE8gr

Stapes Surgery Teaching Tool: A Simple and Stable Technique

Abstract

Stapedotomy followed by placement of a piston prosthesis is the mainstay for surgical management of otosclerosis primarily undertaken to improve hearing in patients. Although a simple and elegant procedure, prosthesis placement in stapes surgery is difficult to master. Improper surgical technique or improper placement of prosthesis may result in complications which may require revision surgery. We here describe a training technique that is simple, inexpensive, improves the skills and can be done using easily available materials such as a disposable syringe, stapler pin and micro-forceps. Regular practice with this training module minimizes surgical time and can even be done just prior to the surgery, however, this is not a substitute for temporal bone dissections.

https://ift.tt/2q1PfjQ

Bilateral Foreign Body Bronchus

Abstract

Foreign body of aerodigestive tract is one of the most common emergency which all the otolaryngologists do come across in the pediatric patients. Among the airway and digestive tract foreign bodies, airway foreign bodies always possess major risk. Only 47% cases will give a probable positive history. Most of the time the airway foreign bodies are radiolucent. Apart from the indirect signs like hyperinflation, collapse or pneumothorax there are no direct evidences regarding the type and number of foreign bodies on radiographs. The chances of having multiple foreign bodies in the same bronchus or in both the bronchi are not remote. Babies presenting with foreign bodies in bilateral bronchus have graver prognosis than the babies with unilateral foreign bodies. Here we want to share our experience in managing 7 cases of bilateral foreign body bronchus.

https://ift.tt/2JdE7ZV

Incidence and Treatment Outcomes of Post Traumatic BPPV in Traumatic Brain Injury Patients

Abstract

The aim of this study is to assess the incidence of post traumatic BPPV and evaluate its treatment outcomes in mild and moderate traumatic head injury patients. The study population consisted of 128 patients (89 male:39 female) who were admitted with head and neck injury (Motor Vehicle Accident, Blow to the head, Fall from Height, Whiplash injury) as inpatients in Department of Neurosurgery in Tertiary care hospital in Kerala during a 2 month period from 1st April 2014 to 31st May 2014. The age range was 10–70 years and mean 39.8 with standard deviation 15.5. All cases were evaluated and serially followed up to a period of 6 months in Department of Otorhinolaryngology. In our study, the number of patients with mild injuries (Glasgow coma scale 13–15) were 108 and moderate injury (Glasgow coma scale 9–12) were 20. We found out that post traumatic BPPV was found to be 17% of the traumatic brain injury patients. All patients were treated with particle re-positioning maneuvers and were followed up for a period of 6 months. Recurrence were reported in 9 (40.9%) patients. In these patients re positioning maneuvers were repeated.

https://ift.tt/2q1NEKG

Effectiveness of Over-The-Counter Intranasal Preparations: A Randomized Trial

Abstract

To compare the effectiveness of over-the-counter normal saline with nasal decongestant drops for the symptomatic relief of nasal congestion, and to determine if nasal drops used alone are effective in the treatment of patients suffering from nasal congestion. Prospective, randomized double blinded study. Otorhinolaryngology Outpatient Department. Patients suffering from nasal congestion and similar symptoms such as nasal discharge, dryness, crusting, sneezing, itching and loss of smell. Resolution of symptoms based on visual analog scale and objective findings on anterior rhinoscopy. Chi-square test was done for comparison between the saline and decongestant groups. Subgroup analysis was done for patients on additional medication such as antibiotics. The p value is 0.701671 for the effectiveness of saline against that of decongestant, thus no significant difference exists between them for the relief of nasal congestion. The p value is 0.007497 for those on antibiotics and those that were treated only with nasal drops, thus showing a significant difference (level of significance being p < 0.05). The effectiveness of both nasal saline and decongestant drops in bringing about relief of nasal congestion is similar, and both of them may also cause headache though the mechanism is not well understood from this study. Relief might be primarily obtained with the help of oral medication and not the use of nasal drops.

Level of evidence: Single-center randomized trial, level II b.

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In This Issue

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EfrEF and the transcription regulator ChlR are required for chlorhexidine stress response in Enterococcus faecalis V583 [PublishAheadOfPrint]

Enterococcus faecalis is an opportunistic pathogen and leading cause of healthcare-associated infections. Daily chlorhexidine gluconate (CHG) bathing of patients is generally regarded as an effective strategy to reduce the occurrence of healthcare-associated infections. It is likely that E. faecalis are frequently exposed to inhibitory and sub-inhibitory CHG in clinical settings. The goal of this study was to investigate how the vancomycin-resistant strain E. faecalis V583 transcriptionally responds to and tolerates stress from CHG. We used transcriptome (microarray) analysis to identify genes up-regulated by E. faecalis V583 in response to CHG. The genes efrE (EF2226) and efrF (EF2227), encoding a heterodimeric ABC transport system, were the most highly up-regulated genes. efrEF expression was induced by CHG at concentrations several two-fold dilutions below the MIC. Deletion of efrEF increased E. faecalis V583 susceptibility to CHG. We found that ChlR, a MerR-like regulator encoded upstream of efrEF, mediated the CHG-dependent up-regulation of efrEF, and deletion of chlR also increased chlorhexidine susceptibility. Overall, our study gives insight into E. faecalis stress responses to a commonly used antiseptic.

https://ift.tt/2EcDQm9

The Cardiovascular safety of Macrolides: A Systematic review, meta-analysis and network meta-analysis [PublishAheadOfPrint]

Background: Studies reporting an increased risk for cardiac toxicities with macrolide antibiotics have raised concern regarding their cardiovascular safety. We sought to assess the cardiac safety of Macrolide antibiotics as a class and of the individual agents by conducting a systematic review and network meta-analysis.

Methods: MEDLINE, EMBASE and the Cochrane Library were searched up to February 2018, for studies reporting on cardiovascular outcomes with macrolides. We followed the PRISMA 2009 guidelines for data selection and extraction. Outcomes were pooled using random effects models and odds ratios (OR) and 95% confidence intervals (CI) were calculated for: arrhythmia, cardiovascular death, and myocardial infarction (MI).

Results: A total of 33 studies and 22,601,032 subjects were retrieved and included in the current meta-analyses. Macrolide use was not associated with the risk of arrhythmia or cardiovascular mortality. In the primary analysis macrolide use was associated with a small, but statistically significant 15% increase in risk for MI (OR=1.15 [95%CI 1.02-1.30]). In indirect network meta-analysis, erythromycin and clarithromycin were ranked considerably more likely associated with a higher risk for MI, and significantly associated with increased risk of MI compared to azithromycin (OR=1.58 [95% CI 1.18-2.11] and OR=1.41 [95% CI 1.11-1.81], respectively).

Conclusions: Our findings indicate macrolide antibiotics as a group are associated with a significant risk for MI, but not for arrhythmia and cardiovascular mortality. Among the macrolides, erythromycin and clarithromycin were associated with greater risk of MI. However, it is possible the association between macrolide use and risk of MI is the result of residual confounding.

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The mechanistic basis of pH-dependent 5-flucytosine resistance in Aspergillus fumigatus [PublishAheadOfPrint]

The antifungal drug 5-flucytosine (5FC), a derivative of the nucleobase cytosine, is licenced for treatment of fungal diseases however it is rarely used as a monotherapeutic to treat Aspergillus infection. Despite being potent against other fungal pathogens, 5FC has limited activity against A. fumigatus when standard in vitro assays are used to determine susceptibility. However, in modified in vitro assays where the pH is set to pH 5 the activity of 5FC increases significantly.

Here we provide evidence that fcyB, a gene that encodes a purine-cytosine permease orthologous to known 5FC importers is downregulated at pH 7 and is the primary factor responsible for the low efficacy of 5FC at pH 7. We also uncover two transcriptional regulators that are responsible for repression of fcyB and consequently mediators of 5FC resistance, the CCAAT binding complex (CBC) and the pH regulatory protein PacC. We propose that the activity of 5FC might be enhanced by perturbation of factors that repress fcyB expression such as PacC or other components of the pH sensing machinery.

https://ift.tt/2H6xZCe

Absence of azole or echinocandin resistance in Candida glabrata isolates in India despite background prevalence of strains with defects in DNA mismatch repair pathway [PublishAheadOfPrint]

Candida glabrata infections are increasing world-wide and exhibit greater rates of antifungal resistance than other species. DNA mismatch repair (MMR) gene deletions, such as msh2, in C. glabrata resulting in a mutator phenotype has recently been reported to facilitate rapid acquisition of antifungal resistance. This study determined the antifungal susceptibility profile of 210 C. glabrata isolates, in 10 hospitals in India and investigated the impact of novel MSH2 polymorphisms on mutation potential. No echinocandin or azole resistant strains were detected among C. glabrata isolates and no mutations in FKS hotspot regions supporting our in vitro susceptibility testing results. CLSI antifungal susceptibility data showed MICs of anidulafungin (GM, 0.12μg/ml) and micafungin (GM, 0.01μg/ml) were lower and below the susceptibility breakpoint as compared to that for caspofungin (CAS GM, 1.31μg/ml). Interestingly, 69% of C. glabrata strains sequenced contained six nonsynonymous mutations in MSH2 i.e., V239L, and novel mutations E459K, R847C, Q386K, and T772S. Functional analysis of MSH2 mutations revealed that 49% of tested strains (40/81) contained a partial loss-of-function MSH2 mutation. The novel MSH2 substitution Q386K produced greater frequencies of CAS- resistant colonies upon expression in msh2. However, expression of two other novel MSH2 alleles i.e., E459K or R847C did not confer selection of resistant colonies confirming that not all mutations in MSH2 MMR pathway affects its function or generate a phenotype that is resistant to antifungal drugs. The lack of drug resistance prevented any correlations to be drawn with respect to MSH2 genotype

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In vitro and in vivo activities of DS-2969b, a novel GyrB inhibitor, and its water-soluble prodrug, DS11960558, against methicillin-resistant Staphylococcus aureus [PublishAheadOfPrint]

DS-2969b is a novel GyrB inhibitor under clinical development. In this study, the in vitro activity of DS-2969b and in vivo activities of DS-2969b and its water-soluble prodrug, DS11960558, against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. DS-2969b inhibited the supercoiling activity of S. aureus DNA gyrase and the decatenation activity of its topoisomerase IV. DS-2969b showed antibacterial activity against Gram-positive aerobes but not against Gram-negative aerobes, except Moraxella catarrhalis and Haemophilus influenzae. DS-2969b was active against MRSA with an MIC₉₀ of 0.25 μg/mL, which was 8-fold lower than that of linezolid. The presence of a pulmonary surfactant did not affect the MIC of DS-2969b. DS-2969b showed time-dependent slow killing against MRSA. The frequency of spontaneous resistance was less than 6.2 x 10^-10 in all four S. aureus isolates at 4x MIC of DS-2969b. In a neutropenic MRSA-induced murine muscle infection model, DS-2969b was more efficacious than linezolid by both subcutaneous and oral routes. DS-2969b and DS11960558 showed efficacy in a neutropenic murine MRSA lung infection model. Pharmacokinetics and pharmacodynamics of DS-2969b and DS11960558 against MRSA were characterized in a neutropenic murine thigh infection model; time above MIC of free drug (f T_MIC) correlated best with in vivo efficacy, and static %f T_MIC was 43—49%. Sufficient f T_MIC was observed in the oral phase 1 multiple-ascending dose study of DS-2969b at 400 mg once a day. These results suggest that DS11960558 and DS-2969b have potential for intravenous-to-oral step-down therapy for treating MRSA infections with higher efficacy than linezolid.

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Pharmacokinetics of daptomycin in critically ill pediatric patients [PublishAheadOfPrint]

Daptomycin pharmacokinetics (10 mg/kg once daily) was studied in 4 critically ill pediatric patients aged 8-14 yrs. Area under the curve (AUC_0-) of plasma concentrations on day 1 ranged between 123.8-663.9 μg ⋅ h/ml, with lower values observed in septic and burn patients; clearance ranged between 15.1-80.7 ml/h/kg. Higher than recommended doses of daptomycin may be needed in septic children to ensure optimal drug exposure. Inter-patient variability may suggest a role for therapeutic drug monitoring.

https://ift.tt/2H3vUXq

ST273 carbapenem-resistant Klebsiella pneumoniae carrying blaNDM-1 and blaIMP-4 [PublishAheadOfPrint]

A carbapenem-resistant Klebsiella pneumoniae was recovered from human blood. Its whole genome sequence was obtained using both Illumina and long-read MinION sequencing. The strain belongs to ST273, which has been found recently and caused an outbreak in Southeast Asia. It has two carbapenemase genes bla_NDM-1 (carried by an ST7 IncN self-transmissible plasmid) and bla_IMP-4 (located on an self-transmissible IncHI5 plasmid). Non-KPC-producing ST237 may represent a lineage of carbapenem-resistant K. pneumoniae, which warrants further monitoring.

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Avibactam Pharmacokinetic/Pharmacodynamic Targets [PublishAheadOfPrint]

Avibactam is a novel non-β-lactam β-lactamase inhibitor that has been approved in the USA and Europe for use in combination with ceftazidime. Combinations of avibactam with aztreonam or ceftaroline fosamil have also been clinically evaluated. Until recently, there has been very little precedence of which pharmacokinetic/pharmacodynamic (PK/PD) indices and magnitudes are appropriate to use for β-lactamase inhibitors in population PK modeling for analyzing potential doses and susceptibility breakpoints. For avibactam, several preclinical studies using different in vitro and in vivo models have been conducted to identify the PK/PD index of avibactam and the magnitude of exposure necessary for effect in combination with ceftazidime, aztreonam, or ceftaroline fosamil. The PD driver of avibactam critical for restoring the activity of all three partner β-lactams was found to be time-dependent rather than concentration-dependent, and was defined as the time that the concentration of avibactam exceeded a critical concentration threshold (%fT>C_T). The magnitude of C_T and the time that this threshold needed to be exceeded to elicit particular PD endpoints varied depending on the model and the partner β-lactam. This review describes the preclinical studies used to determine the avibactam PK/PD target in combination with its β-lactam partners.

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Overexpression of the efflux pumps SmeVWX and SmeDEF is a major cause of resistance to cotrimoxazole in Stenotrophomonas maltophilia [PublishAheadOfPrint]

Cotrimoxazole is one of the antimicrobials of choice for treating Stenotrophomonas maltophilia infections. Most works on the molecular epidemiology of resistance to this drugs combination are based in the analysis of sul genes. Nevertheless, the existence of clinical cotrimoxazole resistant S. maltophilia isolates that do not harbor sul genes has been reported. To investigate potential mutations that can reduce the susceptibility of S. maltophilia to cotrimoxazole, spontaneous S. maltophilia cotrimoxazole resistant mutants isolated under different cotrimoxazole concentrations were studied. All mutants presented phenotypes compatible with the overexpression of either SmeVWX (94.6%) or SmeDEF (5.4%). Indeed, the analysis of a selected set of strains showed that overexpression of either one or another of these efflux pumps, which was due to mutations in their regulators smeRv and smeT respectively, was the cause of cotrimoxazole resistance. None other efflux pump was overexpressed in any of the studied mutants, indicating that they do not participate in the observed resistance phenotype. The analysis of mutants overexpressing or lacking SmeDEF or SmeVWX shows that SmeDEF contributes to intrinsic and acquired resistance to cotrimoxazole in S. maltophilia whereas SmeVWX only contributes to acquired resistance. It is important to highlight that all mutants were less susceptible to other antibiotics, including chloramphenicol and quinolones. Since both SmeVWX and SmeDEF are major determinants of quinolone resistance, the potential cross-selection of resistance to cotrimoxazole and quinolones, when either of the antimicrobial is used, is of particular concern for the treatment of S. maltophilia infections.

https://ift.tt/2Ee75VO

Pyocyanin Inhibits Chlamydia Infection by Disabling Infectivity of the Elementary Body and Disrupting Intracellular Growth [PublishAheadOfPrint]

The obligate intracellular bacterium Chlamydia is a widespread human pathogen that causes serious problems including (but not limited to) infertility and blindness. Our search for novel antichlamydial metabolites from marine-derived microorganisms led to isolation of pyocyanin, a small compound from Pseudomonas aeruginosa. Pyocyanin is an effective antichlamydial for all three Chlamydia spp. tested. It has an IC₅₀ of 0.019 ~ 0.028 μM, which is comparable to the IC₅₀ of tetracycline. At concentrations as low as 0.0039 μM, pyocyanin disables infectivity of the chlamydial elementary body (EB). At 0.5 μM or higher concentrations, continuous presence of pyocyanin also inhibits chlamydial growth in the inclusion during later stages of the developmental cycle. Oxidative stress, a major known antimicrobial mechanism of pyocyanin, appears to be responsible for only the inhibition of bacterial growth but not the disinfection of EBs. Pyocyanin is well-tolerated by probiotic vaginal Lactobacillus spp. Our findings suggest that pyocyanin is of therapeutic value for chlamydial infections, and can serve as a valuable chemical probe for studying chlamydial biology.

https://ift.tt/2GMZhQ5

SCY-078, a Novel Oral Glucan Synthase Inhibitor, for the Treatment of Invasive Aspergillosis: Evaluation of Antifungal Activity Singly and in Combination [PublishAheadOfPrint]

Invasive aspergillosis remains a major cause of death among the immunocompromised population and those receiving long-term immunosuppressive therapy. In light of increased azole resistance, variable outcomes with existing echinocandin mono and combination therapy, and persistent high mortality rates, new antifungal agents for the treatment of invasive aspergillosis are clearly needed.

SCY-078 is the first in class triterpenoid antifungal, a novel class of glucan synthase inhibitors, with broad in vitro and in vivo activity against a broad spectrum of Candida and Aspergillus. In vitro testing of clinical strains of Aspergillus fumigatus and non-fumigatus strains showed potent fungistatic activity of SCY-078 (minimum effective concentration, MEC₉₀ = 0.125 μg/ml) as compared with amphotericin B (MIC₉₀ = 8 μg/ml) and voriconazole (MIC₉₀ = 2 μg/ml). Combination testing of SCY-078 with isavuconazole or voriconazole demonstrated synergistic activity against the majority of the azole-susceptible strains tested, and SCY-078 in combination with amphotericin B was synergistic against the azole-susceptible strains, as well as one known resistant cyp51A mutant. SCY-078 may be an important additional antifungal for first-line or salvage mono or combination treatment of invasive aspergillosis.

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Tomatidine, a lead antibiotic molecule that targets Staphylococcus aureus ATP synthase subunit C [PublishAheadOfPrint]

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of deadly hospital-acquired infections. The discovery of anti-Staphylococcus antibiotics and new classes of drugs not susceptible to the mechanisms of resistance shared among bacteria is imperative. We recently showed that tomatidine (TO), a steroidal alkaloid from solanaceous plants, possesses potent antibacterial activity against S. aureus small colony variants (SCVs), the notoriously persistent form of this bacterium that has been associated with recurrence of infections. Here, using genomic analysis of in vitro-generated TO-resistant S. aureus strains to identify mutations in genes involved in resistance, we identified the bacterial ATP synthase as the cellular target. Sequence alignments were performed to highlight the modified sequences and the structural consequences of the mutations were evaluated in structural models. Overexpression of the atpE gene in S. aureus SCVs or introducing the mutation found in the atpE gene of one of the high-level TO-resistant S. aureus mutant into the Bacillus subtilis atpE gene provided resistance to TO and further validated the identity of the cellular target. FC04-100, a TO derivative which also possesses activity against non-SCV strains, prevents high-level resistance development in prototypic strains and limits the level of resistance observed in SCVs. An ATP synthesis assay allowed the observation of a correlation between antibiotic potency and ATP synthase inhibition. The selectivity index (inhibition of ATP production by mitochondria vs. bacterial ATP synthase) is estimated to be >10⁵-fold for FC04-100.

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Relebactam is a Potent Inhibitor of the KPC-2 {beta}-Lactamase and Restores the Susceptibility of Imipenem Against KPC-Producing Enterobacteriaceae [PublishAheadOfPrint]

The imipenem-relebactam combination is in development as a potential treatment regimen for infections caused by Enterobacteriaceae possessing complex β-lactamase backgrounds. Relebactam is a β-lactamase inhibitor that possesses the diazabicyclooctane core similar to avibactam, however relebactam's R1 side chain also includes a piperidine ring compared to the carboxyamide of avibactam. Here, we investigated the inactivation of Klebsiella pneumoniae carbapenemase (KPC-2), the most widespread class A carbapenemase, by relebactam and performed susceptibility testing with imipenem-relebactam using KPC-producing clinical isolates of Enterobacteriaceae. Minimal inhibitory concentration (MIC) measurements using agar dilution methods revealed that all 101 clinical isolates of KPC-producing Enterobacteriaceae (K. pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Citrobacter freundii, Citrobacter koseri, and Escherichia coli) were highly susceptible to imipenem-relebactam (MICs ≤ 2 mg/L). Relebactam inhibited KPC-2 with a k₂/K value of 24,750 M^-1s^-1 and demonstrated a slow k_off of 0.0002 s^-1. Biochemical analysis using time-based mass spectrometry to map intermediates revealed that the KPC-2-relebactam acyl-enzyme complex was stable for up to 24 hours. Importantly, desulfation of relebactam was not observed using mass spectrometry. Desulfation and subsequent deacylation has been observed during the reaction of KPC-2 with avibactam. Upon molecular dynamics simulations of relebactam in the KPC-2 active site, we found that in comparison to the KPC-2-avibactam, the positioning of active site water molecules is less favorable for desulfation. In the acyl-complexes, the water molecules are within 2.5-3 Å of the avibactam sulfate, however more than 5-6 Å from the relebactam sulfate. As a result, we propose that the KPC-2-relebactam acyl-complex is more stable than the KPC-2-avibactam acyl-enzyme complex. The clinical implications of this difference are not currently known.

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Fungicidal potency and mechanisms of {theta}-defensins against multi-drug resistant Candida species [PublishAheadOfPrint]

Systemic candidiasis is a growing health care concern becoming even more challenging due to the growing frequency of infections caused by multidrug resistant (MDR) Candida spp. Thus there is an urgent need for new therapeutic approaches to candidiasis, including strategies bioinspired by insights into natural host defense against fungal pathogens. The antifungal properties of -defensins, macrocyclic peptides expressed in tissues of Old World monkeys, were investigated against a panel of drug sensitive and drug resistant clinical isolates of C. albicans and non-albicans Candida spp. Rhesus -defensin 1 (RTD-1), the prototype -defensin, was rapidly and potently fungicidal against drug sensitive and MDR C. albicans strains. Fungal killing occurred by cell permeabilization that was temporally correlated with ATP release and intracellular accumulation of reactive oxygen species (ROS). Killing by RTD-1 was compared with that of histatin 5 (Hst 5), an extensively characterized anticandidal peptide expressed in human saliva. RTD-1 killed C. albicans much more rapidly and at >200-fold lower concentration than Hst 5. Unlike Hst 5, the anticandidal activity of RTD-1 was independent of mitochondrial ATP production. Moreover, RTD-1 was completely resistant to Candida proteases for 2 h under conditions that rapidly and completely degraded Hst 5. Minimal inhibitory and fungicidal concentrations (MIC/MFC) of 14 natural -defensins isoforms against drug resistant C. albicans isolates identified peptides that are more active than amphotericin B and/or caspofungin against fluconazole resistant organisms, including MDR C. auris. These results point to the potential of macrocyclic -defensins as structural templates for design of antifungal therapeutics.

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The Combination of Daptomycin plus Fosfomycin has Synergistic, Potent and Rapid Bactericidal Activity against Methicillin-Resistant Staphylococcus aureus (MRSA) in a Rabbit Model of Experimental Endocarditis (EE). [PublishAheadOfPrint]

This study aims to investigate whether the addition of fosfomycin or cloxacillin to daptomycin provides better outcomes in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) experimental aortic endocarditis in rabbits. Five MRSA strains were used to perform in vitro time-kill studies at standard (105) and high (108) inocula. Combined therapy was compared with daptomycin monotherapy treatment in the MRSA experimental endocarditis model. A human-like pharmacokinetics model was applied and the equivalents of cloxacillin 2g/4hiv, fosfomycin 2g/6h iv and daptomycin 6-10mg/kg/d iv were administered. The combination of daptomycin and fosfomycin or cloxacillin was synergistic in the five strains tested at both inocula. A bactericidal effect was detected in four out of five strains tested with both combinations. The MRSA-277 strain (vancomycin MIC, 2 mcg/mL) was used for the experimental endocarditis model. Daptomycin plus fosfomycin significantly improved the efficacy of daptomycin monotherapy at 6 mg/kg/d in terms of both the proportion of sterile vegetations (100% vs. 72%, P=.046) and the decrease in the density of bacteria within the vegetations (P=.025). Daptomycin plus fosfomycin was as effective as daptomycin monotherapy at 10 mg/kg/d (100% vs. 93%, P=1.00) and had similar activity to daptomycin plus cloxacillin when daptomycin was administered at 6 mg/kg/d (100% vs. 88%, P=0.48). Daptomycin non-susceptibility was not detected in any of the isolates recovered from vegetations. In conclusion, for the treatment of MRSA experimental endocarditis, the combination of daptomycin plus fosfomycin showed synergistic and bactericidal activity.

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Cutis laxa associated monoclonal gammopathy: 14 new cases and review of the literature

https://ift.tt/2q12dhT

In Mice, Long-Lasting Brain Proteins Offer Clues to How Memories Last a Lifetime

In the tiny brain space where two nerve cells meet, chemical and electric signals shuttle back and forth, a messaging system that ebbs and flows in those synaptic spaces, sometimes in ways that scientists believe aid and abet learning and memory. But because most of the proteins found in those synapses die and renew themselves so rapidly, scientists have had a hard time pinning down how synapses are stable enough to explain the kind of learning and memory that lasts a lifetime. 

https://ift.tt/2Jc3MCk

A Study of Optical Imaging With Light From Radiotracers in Cancer Patients

Condition:   Thyroid Cancer
Intervention:   Diagnostic Test: Cerenkov luminescence imaging.
Sponsor:   Memorial Sloan Kettering Cancer Center
Recruiting

https://ift.tt/2ImIfp3

Efficacy and Safety Study of Tisotumab Vedotin for Patients With Solid Tumors

Conditions:   Colorectal Neoplasms;   Carcinoma, Non-Small-Cell Lung;   Exocrine Pancreatic Cancer;   Carcinoma, Squamous Cell of Head and Neck
Intervention:   Drug: tisotumab vedotin
Sponsors:   Seattle Genetics, Inc.;   Genmab
Not yet recruiting

https://ift.tt/2GLIXPI

Assessment and Prediction of Cetuximab-Induced Hypersensitivity Reactions Using Cetuximab Specific IgE Detection

Conditions:   Tumor Disease Including Colorectal Cancer;   Head & Neck Squamous Cell Carcinoma
Intervention:  
Sponsor:   Yonsei University
Recruiting

https://ift.tt/2Ee2naK

Issue Information

Dermatologic Therapy, Volume 31, Issue 2, March/April 2018.


https://ift.tt/2pYgXxZ

Imaging evaluation of electrode placement and effect on electrode discrimination on different cochlear implant electrode arrays

Abstract

Objective

The aim of the present study is to evaluate the effect of electrode discrimination based on electrode to modiolus distance in different cochlear implant models, using image information to estimate the outcomes after an implantation on electrode discrimination

Methods

A descriptive prospective randomized study performed during 16 months. A psychoacoustic platform was used to evaluate patients' electrode discrimination capabilities of patients. For the acquisition of the images, a cone beam computed tomography was used to assess postcochlear implantation of electrodes' position. We considered two other new measurements: the intracochlear position index, which indicates how far is the electrode from the modiolar wall, and the homogeneity factor (HF), which provides us with information about the distance between the electrodes and the modiolus

Results

21 postlingually deaf adults showing different CI models [CI522 (n = 7), CI512 (n = 7), and CI532 (n = 7)] that corresponded to the lateral and perimodiolar array electrodes. The average success rate of the CI522 group was 47%, of the CI512 group was 48%, and of the CI532 group was 77%. There is statistically significant difference between groups CI532–CI522 (p = 0.0033) and CI532–CI512 (p = 0.0027)

Conclusion

The Nucleus CI532 offers a better perimodiolar placement. HF and IPI measurements provide information about the electrodes location inside the cochlea, being related to electrode discrimination.

https://ift.tt/2H4U6sq

Media Advisory: Free Distracted Driving Awareness Events to Educate Attendees About Safe Behaviors Behind the Wheel

As part of the Maryland Trauma System distracted driving awareness statewide initiative for Distracted Driving Awareness Month, some Johns Hopkins Health System trauma centers will host events to educate people about the dangers of distracted driving. The events are free and open to the public.

https://ift.tt/2Edrmus

Poor oral intake causes enteral nutrition dependency after concomitant chemoradiotherapy for pharyngeal cancers

Abstract

Purpose

To identify precipitating factors responsible for enteral nutrition (EN) dependency after concomitant chemoradiotherapy (CCRT) of head and neck cancers and to examine their statistical correlations.

Methods

Factors related to feeding condition, nutritional status, disease, and treatment of 26 oropharyngeal and hypopharyngeal cancer patients who received definitive CCRT were retrospectively investigated by examining their medical records. The days of no oral intake (NOI) during hospitalization and the months using enteral nutrition after CCRT were counted as representing the feeding condition, and the changes in body weight (BW) were examined as reflecting nutritional status. The factors related to EN dependency after CCRT were analyzed.

Results

Long duration of total NOI (≥ 30 days) and maximum NOI ≥ 14 days were significant predictors of EN dependency. Decreased BW (≥ 7.5 kg) was the next predictor identified, but it was not significant. Multivariate analysis showed that the total duration of NOI was more correlated with EN dependency than changes in BW.

Conclusions

A long duration of NOI was more strongly related to EN dependency than nutritional factors.

https://ift.tt/2GK1ls7

Chemicals in Meat Cooked at High Temperatures and Cancer Risk

A fact sheet that explains how certain chemicals are formed in meat that is cooked using high-temperature methods, such as pan frying or grilling, and describes the results of research on the relationship between consumption of these chemicals and cancer risk.

https://ift.tt/2erZPZJ

Angiolymphoid hyperplasia with eosinophilia: a case report

Angiolymphoid hyperplasia with eosinophilia is a benign neoplasm that includes blood vessel proliferation and a dense eosinophilic inflammatory infiltrate. Mostly, it affects middle-aged adults manifesting as ...

https://ift.tt/2q1XyMi

Potassium titanyl phosphate laser-induced inflammatory response and extracellular matrix turnover in rabbit vocal fold scar

Abstract

Purpose

The objectives of this study were to observe the regulating effect of KTP laser and Nd:YAG laser in the repair of vocal fold scars.

Methods

All rabbits were injured in the muscular layer with a sharp instrument, and then the vocal folds were treated with a KTP laser and a Nd:YAG laser at a power of 2, 4, 6 and 8 W 1 month after the injury. One month after treatment, the rabbits were killed and the throats were removed to detect changes in histology and gene expression of the vocal fold scar after laser therapy.

Results

The best efficacy of all KTP laser treatment groups was the KTP laser 6 W group. Regarding the detection of gene expression, in the KTP laser 6 W and Nd:YAG laser 6 W groups, col-3A1 was decreased compared to the scar group (P < 0.05), and col-1A1 was decreased only in the KTP laser 6 W group (P < 0.05). TGF-β1 levels in the two groups were lower than in the scar group. There were also significant differences in the levels of IL-1β, COX-2 and TNF-α in the two laser groups compared with the scar group (P < 0.05).

Conclusion

KTP laser and Nd:YAG laser treatments for vocal fold scars have particular therapeutic effects. The KTP laser may be better than the Nd:YAG laser for the regulation of vocal fold scars.

Level of evidence

NA.

https://ift.tt/2pZE3nE

Organ preservation surgery for patients with T4a laryngeal cancer

Abstract

Purpose

Surgical preservation of laryngeal function is very challenging in patients with advanced SCCL, especially those of stage T4a. The purpose of this study was to assess the feasibility of organ preservation surgery for patients with T4a squamous cell carcinoma of the larynx (SCCL).

Methods

We enrolled 32 patients with T4a SCCL and performed organ preservation surgery on them. Surgical details and perioperative morbidity were described, functional and oncologic outcomes were also evaluated.

Results

All patients underwent supracricoid subtotal laryngectomy with unilateral or bilateral neck dissection, restoring laryngeal function via direct anastomosis of the cricoid cartilage and tongue base. The patients recovered well and exhibited relatively acceptable survival duration, with a 5-year overall survival rate of 62.5%. Most patients commenced oral intake within 2 weeks, and aspiration was commonly observed. Subjective functional outcomes indicated a relatively acceptable swallowing function and voice quality.

Conclusion

Our retrospective analysis of 32 patients with T4a SCCL showed that successful organ preservation surgery is safe and reliable, and associated with a relatively acceptable disease-free survival, normal swallowing function, and acceptable voice quality. More patients with T4a SCCL who wish to preserve the larynx should be considered for organ preservation surgery.

https://ift.tt/2GtZqJa

In response to Double‐blind, placebo‐controlled study with alginate suspension for laryngopharyngeal reflux disease

The Laryngoscope, EarlyView.


https://ift.tt/2GwOohS

A novel technique for tracheal reconstruction using a resorbable synthetic mesh

The Laryngoscope, EarlyView.


https://ift.tt/2pWNKEg

A case of Dupuytren’s disease managed with viable cryopreserved placental membrane adjunct to open palmar fasciectomy

Abstract

Dupuytren's disease (DD) is a rare connective tissue disorder resulting in progressive fibrosis and thickening of the palmar fascia, and contracture of the fingers due to excessive collagen deposition. Staged surgical interventions are reserved for severe cases, yet worsening of fibrosis and contracture of fingers post-surgery, has been reported to have a recurrence rate as high as 85%. Here, the authors report on use of viable cryopreserved placental membrane (vCPM) allograft as an adjunct to open fasciectomy. In a patient with debilitating bilateral DD contractures of >20 years duration, this novel approach resulted in a 34.8% range of motion (ROM) improvement and ability to fully extend all digits of the right hand. No adverse events were recorded. At 1 year post-surgery, the patient has no decrease in ROM. Results indicate that vCPM incorporation in open fasciectomy may provide benefit in reducing contracture recurrence in DD patients.

https://ift.tt/2Jd0vmn

Severe acute gallstone pancreatitis with diffuse hemorrhagic gastritis

Abstract

A 67-year-old male presented with acute pancreatitis secondary to gallstones, also known as acute biliary pancreatitis, and subsequently developed gastric outlet obstruction and was transferred to our hospital. A gastro-jejunal feeding tube was placed and an open cholecystectomy was performed. The patient had a pancreatic drain placed for interval increase in pancreatic necrosis and then nearly exsanguinated from gastroduodenal artery pseudoaneurysm bleed. This was managed by coiling the gastroduodenal artery. The patient underwent a pancreatic necrosectomy with malencot drain placement and developed a post-operative upper gastrointestinal bleeding. An EGD showed diffuse gastritis, but no varices. And 18 days later the patient rebled, with the same diffuse gastritis. After further complications the patient elected to receive palliative care at a hospice facility. We are presenting this unusual case of diffuse, hemorrhagic gastritis after acute necrotizing pancreatitis.

https://ift.tt/2EcFfcz

Prognostic implications of CD44, NANOG, OCT4, and BMI1 expression in tongue squamous cell carcinoma

Head &Neck, EarlyView.


https://ift.tt/2Io8hbL

Investigation of thyroid nodules: A practical algorithm and review of guidelines

Head &Neck, EarlyView.


https://ift.tt/2H4Du4m

Neck hematoma after major head and neck surgery: Risk factors, costs, and resource utilization

Head &Neck, EarlyView.


https://ift.tt/2IjmeI0

Glottic cancer in patients without complaints of hoarseness

Head &Neck, EarlyView.


https://ift.tt/2GKNRwd

Subdural Hemorrhage after Scoliosis and Detethering of Cord Surgery

Introduction. Intracranial hypotension may occur when CSF leaks from the subarachnoid space. Formation of intracranial, subdural, and subarachnoid hemorrhage has been observed after significant CSF leak as seen in lumbar puncture or ventricular shunt placement. However, very few cases, referring to these remote complications following spine surgery, have been described in literature. We present a case of a 10-year-old male child operated for idiopathic scoliosis with low-lying conus medullaris who postoperatively developed subdural hemorrhage. Case Report. A case of a 10-year-old male operated for idiopathic scoliosis with low-lying conus medullaris is presented. To correct this, detethering was done at the L3 level, laminectomy was done from L2 to L3 with pedicular screw fixation from T3 to L2, and bone grafting with right costoplasty was done from the 3rd to the 6th ribs. On the 5th day postoperatively, the patient developed convulsions and drowsiness and recovered subsequently by postoperative day 7. Conclusion. We report a rare case of an acute intracranial subdural hemorrhage caused by intracranial hypotension following scoliosis and detethering of cord surgery. This report highlights the potential morbidity associated with CSF leak occurring after this surgery.

https://ift.tt/2JaCV9A

Thirty‐two Japanese cases of infantile hemangiomas treated with oral propranolol

The Journal of Dermatology, EarlyView.


https://ift.tt/2H2E9Df

Successful treatment of cutaneous phaeohyphomycosis caused by Exophiala lecanii‐corni with voriconazole

The Journal of Dermatology, EarlyView.


https://ift.tt/2uCN5gb

Case of photosensitivity after the administration of olmesartan medoxomil

The Journal of Dermatology, EarlyView.


https://ift.tt/2Gr4iOT

Angiolymphoid hyperplasia with eosinophilia: A case of spontaneous partial regression post‐biopsy

The Journal of Dermatology, EarlyView.


https://ift.tt/2uMfP6j

Cutaneous hydrophilic polymer embolism accompanied by acute renal failure

The Journal of Dermatology, EarlyView.


https://ift.tt/2GpEx1D

Ischemic oculomotor nerve palsy due to hyaluronic acid filler injection

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2pW6CmG

Safety and complications of absorbable threads made of poly‐L‐lactic acid and poly lactide/glycolide: Experience with 148 consecutive patients

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2uFEqcI

Turmeric tonic as a treatment in scalp psoriasis: A randomized placebo‐control clinical trial

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2pXbY1i

A novel heterozygous missense mutation of DSP in a Chinese Han pedigree with palmoplantar keratoderma

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2uEaAFx

Correlations between skin hydration parameters and corneocyte‐derived parameters to characterize skin conditions

Journal of Cosmetic Dermatology, EarlyView.


https://ift.tt/2pW6hQW

Clinical and dermoscopic response predictors in psoriatic patients undergoing narrowband ultraviolet B phototherapy: results from a prospective study

International Journal of Dermatology, EarlyView.


https://ift.tt/2GugFde

A retrospective study of the characteristics of patients with early‐onset compared to adult‐onset hidradenitis suppurativa

International Journal of Dermatology, EarlyView.


https://ift.tt/2uDHHcx

Acquired ichthyosis associated with gastric adenocarcinoma

International Journal of Dermatology, EarlyView.


https://ift.tt/2H5p2Zy

Peristomal psoriasis: an extraintestinal manifestation of inflammatory bowel disease?

International Journal of Dermatology, EarlyView.


https://ift.tt/2GrsTz3

Cutaneous protothecosis in a patient on ustekinumab for psoriasis

International Journal of Dermatology, EarlyView.


https://ift.tt/2pWVFk8