bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity of Tedizolid in Methicillin-Resistant Staphylococcus epidermidis Experimental Foreign Body-Associated Osteomyelitis
Authors: Park Kyung-Hwa , Greenwood-Quaintance Kerryl E. , Schuetz Audrey N. , Mandrekar Jayawant N. , Patel Robin 
Published: November 2016

ABSTRACT

We developed a rat model of methicillin-resistant
Staphylococcus epidermidis
(MRSE) foreign body-associated osteomyelitis and used it to compare tedizolid alone and in combination with rifampin against rifampin alone, vancomycin plus rifampin, and vancomycin alone. A clinical strain of MRSE was inoculated into the proximal tibia, and a stainless steel wire with a precolonized MRSE biofilm was implanted. Following a 1-week infection period, 92 rats received either no treatment (
n
= 17) or 14 days of intraperitoneal tedizolid (
n
= 15), tedizolid plus rifampin (
n
= 15), rifampin (
n
= 15), vancomycin plus rifampin (
n
= 15), or vancomycin (
n
= 15). Quantitative bone and wire cultures were performed after treatment completion and also 1 week after infection in a separate group of five rats. The median quantity of staphylococci in bone after the 1-week infection period was 4.89 log
10
CFU/g bone (interquartile range, 3.83 to 5.33 log
10
CFU/g bone); staphylococci were recovered from all associated wires. A median quantity of staphylococci of 3.70 log
10
CFU/g bone was detected in bones of untreated control rats after 3 weeks. Quantities of staphylococci in bones of all treatment groups except the group receiving vancomycin alone (2.78 log
10
CFU/g) were significantly lower than those for untreated controls, with no staphylococci being detected in the groups receiving rifampin monotherapy, tedizolid-plus-rifampin combination therapy, and vancomycin-plus-rifampin combination therapy. Quantities of staphylococci on wires from all treatment groups that included rifampin were significantly lower than those for untreated controls. No resistance to rifampin, tedizolid, or vancomycin was detected. Tedizolid combined with rifampin was active in a rat model of MRSE foreign body-associated osteomyelitis.
Rifampin-Based Combination Therapy Is Active in Foreign-Body Osteomyelitis after Prior Rifampin Monotherapy
Authors: Brinkman Cassandra L. , Schmidt-Malan Suzannah M. , Mandrekar Jayawant N. , Patel Robin 
Published: November 2016

ABSTRACT

Staphylococcal prosthetic joint infections (PJIs) are associated with biofilm formation, making them difficult to treat; if managed with debridement and implant retention, rifampin-based therapy is usually employed. Rifampin resistance potentially challenges PJI treatment. In investigating the effects of rifampin monotherapy on methicillin-resistant
Staphylococcus aureus
(MRSA) foreign-body osteomyelitis in rats, we previously demonstrated that rifampin resistance was selected but that it disappeared 14 days following rifampin monotherapy (1) and that rifampin resistance occurred less frequently following two rounds than following one round of rifampin monotherapy (2). Here, we compared rifampin monotherapy followed by rifampin-vancomycin combination therapy to rifampin-vancomycin combination therapy alone in experimental MRSA foreign-body osteomyelitis. Animals treated with rifampin monotherapy followed by rifampin-vancomycin combination therapy had decreased quantities of bacteria 14 days following treatment completion (
P
= 0.034) compared to those in animals treated with combination therapy alone. Additionally, some isolates recovered from animals treated with combination therapy alone, although still susceptible to rifampin, had higher MIC, minimum biofilm-inhibitory concentration (MBIC), and minimum biofilm-bactericidal concentration (MBBC) values than those of the inoculating strain. This suggests that rifampin may remain a feasible treatment option in foreign-body-associated orthopedic infections following the selection of rifampin resistance.
Molecular Characterization of OXA-48-Like-Producing Enterobacteriaceae in the Czech Republic and Evidence for Horizontal Transfer of pOXA-48-Like Plasmids
Authors: Skalova Anna , Chudejova Katerina , Rotova Veronika , Medvecky Matej , Studentova Vendula , Chudackova Eva , Lavicka Pavel , Bergerova Tamara , Jakubu Vladislav , Zemlickova Helena , Papagiannitsis Costas C. , Hrabak Jaroslav 
Published: November 2016

ABSTRACT

The aim of this study was to characterize the first cases and outbreaks of OXA-48-like-producing
Enterobacteriaceae
recovered from hospital settings in the Czech Republic. From 2013 to 2015, 22
Klebsiella pneumoniae
isolates, 3
Escherichia coli
isolates, and 1
Enterobacter cloacae
isolate producing OXA-48-like carbapenemases were isolated from 20 patients. Four of the patients were colonized or infected by two or three different OXA-48-like producers. The
K. pneumoniae
isolates were classified into nine sequence types (STs), with ST101 being predominant (
n
= 8). The
E. coli
isolates were of different STs, while the
E. cloacae
isolate belonged to ST109. Twenty-four isolates carried
bla
OXA-48
, while two isolates carried
bla
OXA-181
or
bla
OXA-232
. Almost all isolates (
n
= 22) carried
bla
OXA-48
-positive plasmids of a similar size (∼60 kb), except the two isolates producing OXA-181 or OXA-232. In an ST45
K. pneumoniae
isolate and an ST38
E. coli
isolate, S1 nuclease profiling plus hybridization indicated a chromosomal location of
bla
OXA-48
. Sequencing showed that the majority of
bla
OXA-48
-carrying plasmids exhibited high degrees of identity with the pOXA-48-like plasmid pE71T. Additionally, two novel pE71T derivatives, pOXA-48_30715 and pOXA-48_30891, were observed. The
bla
OXA-181
-carrying plasmid was identical to the IncX3 plasmid pOXA181_EC14828, while the
bla
OXA-232
-carrying plasmid was a ColE2-type plasmid, being a novel derivative of pOXA-232. Finally, sequencing data showed that the ST45
K. pneumoniae
and ST38
E. coli
isolates harbored the IS
1R
-based composite transposon Tn
6237
containing
bla
OXA-48
integrated into their chromosomes. These findings underlined that the horizontal transfer of pOXA-48-like plasmids has played a major role in the dissemination of
bla
OXA-48
in the Czech Republic. In combination with the difficulties with their detection, OXA-48 producers constitute an important public threat.
In Vitro
Activities of Lefamulin and Other Antimicrobial Agents against Macrolide-Susceptible and Macrolide-Resistant Mycoplasma pneumoniae from the United States, Europe, and China
Authors: Waites Ken B. , Crabb Donna M. , Duffy Lynn B. , Jensen Jorgen S. , Liu Yang , Paukner Susanne 
Published: November 2016

ABSTRACT

Lefamulin, an investigational pleuromutilin, was tested against a collection of 18 macrolide-susceptible and 42 macrolide-resistant
Mycoplasma pneumoniae
strains, and the results were compared with those of azithromycin, erythromycin, tetracycline, doxycycline, and moxifloxacin testing. Lefamulin was highly active against all strains tested, with all MICs at ≤0.008 μg/ml. The lefamulin MIC
90
(0.002 μg/ml) for macrolide-resistant strains was the lowest among all drugs tested. Minimum bactericidal concentrations were within 2 dilutions of the MIC values, indicating a bactericidal effect.
Clinical Benefit of Appropriate Empirical Fluoroquinolone Therapy for Adults with Community-Onset Bacteremia in Comparison with Third-Generation-Cephalosporin Therapy
Authors: Lee Ching-Chi , Wang Jiun-Ling , Lee Chung-Hsun , Hsieh Chih-Chia , Hung Yuan-Pin , Hong Ming-Yuan , Tang Hung-Jen , Ko Wen-Chien 
Published: November 2016

ABSTRACT

Both fluoroquinolones (FQs) and third-generation cephalosporins (3rd-GCs) are commonly prescribed to treat bloodstream infections, but comparative efficacies between them were rarely studied. Demographics and clinical characteristics of 733 adults with polymicrobial or monomicrobial community-onset bacteremia empirically treated by an appropriate FQ (
n
= 87) or 3rd-GC (
n
= 646) were compared. A critical illness (respectively, 8.0% versus 19.0%;
P
= 0.01), an initial syndrome with severe sepsis (33.3% versus 50.3%;
P
= 0.003), or a fatal outcome at 28 days (4.6% versus 10.5%;
P
= 0.08) was less common in the FQ group. A total of 645 (88.0%) patients were febrile at initial presentation, and the FQ group with (FQ group versus 3rd-GC group, respectively, 7.6 days versus 12.0 days;
P
= 0.04) and without (3.8 days versus 5.4 days;
P
= 0.001) a critical illness had a shorter time to defervescence than the 3rd-GC group. By the propensity scores, 87 patients with appropriate FQ therapy were matched with 435 treated by 3rd-GC therapy at a ratio of 1:5, and there were no significant differences in terms of bacteremia severity, comorbidity severity, major comorbidities, causative microorganisms, and bacteremia sources between groups. Moreover, crude mortality rates at 28 days (FQ group versus 3rd-GC group, respectively, 4.6% versus 7.8%;
P
= 0.29) did not differ significantly. However, the time to defervescence was shorter in the FQ group (4.2 ± 3.6 versus 6.2 ± 7.6 days;
P
< 0.001). Conclusively in the adults with community-onset bacteremia, appropriate empirical FQ therapy was related to shorter time to defervescence than with 3rd-GC therapy, at least for those without a critical illness.
Novel Detection Strategy To Rapidly Evaluate the Efficacy of Antichlamydial Agents
Authors: Zhang Yan , Xian Yuqi , Gao Leiqiong , Elaasar Hiba , Wang Yao , Tauhid Lamiya , Hua Ziyu , Shen Li 
Published: November 2016

ABSTRACT

Chlamydia trachomatis
infections present a major heath burden worldwide. The conventional method used to detect
C. trachomatis
is laborious. In the present study, a novel strategy was utilized to evaluate the impact of antimicrobial agents on the growth of
C. trachomatis
and its expression of
ompA
promoter-driven green fluorescence protein (GFP). We demonstrate that this GFP reporter system gives a robust fluorescent display of
C. trachomatis
growth in human cervical epithelial cells and, further, that GFP production directly correlates to changes in
ompA
expression following sufficient exposure to antimicrobials. Validation with azithromycin, the first-line macrolide drug used for the treatment of
C. trachomatis
infection, highlights the advantages of this method over the traditional method because of its simplicity and versatility. The results indicate both that
ompA
is highly responsive to antimicrobials targeting the transcription and translation of
C. trachomatis
and that there is a correlation between changing GFP levels and
C. trachomatis
growth. This proof-of-concept study also reveals that the
ompA
-GFP system can be easily adapted to rapidly assess antimicrobial effectiveness in a high-throughput format.
Interplay of Toll-Like Receptor 9, Myeloid Cells, and Deubiquitinase A20 in Periodontal Inflammation
Authors: Crump Katie E. , Oakley Jennifer C. , Xia-Juan Xia , Madu Theandra C. , Devaki Swathi , Mooney Erin C. , Sahingur Sinem E. 
Published: November 2016

ABSTRACT

Toll-like receptor 9 (TLR9)-deficient (TLR9
−/−
) mice are resistant to periodontitis, a disease characterized by a dysbiotic microbiota and deregulated immune response and resulting in tooth loss and various systemic conditions. However, the mechanisms and biological pathways by which TLR9 instigates periodontal inflammation are yet to be identified. In a ligature-induced model of periodontitis, we demonstrate that TLR9
−/−
mice exhibited significantly less alveolar bone loss than their wild-type (WT) counterparts. Consistent with the disease phenotype, gingival tissues showed significantly more inflammatory cell infiltration in the WT ligated but not in the TLR9
−/−
ligated mice compared to the unligated controls. The peritoneal infection model using
Porphyromonas gingivalis
, a keystone pathogen for periodontitis, revealed reduced neutrophils in TLR9
−/−
mice on day 1 postinfection compared to the levels in WT mice. Transcriptomics analyses showed increased expression of A20 (tumor necrosis factor alpha [TNF-α]-induced protein 3 [TNFAIP3]), an inhibitor of the NF-κB pathway and a negative regulator of TLR signaling, in ligated TLR9
−/−
mouse gingival tissues compared to its expression in the WT.
Ex vivo
, TLR9
−/−
bone marrow-derived macrophages produced more A20 than WT cells following
P. gingivalis
challenge. Clinically, A20 was modestly upregulated in human gingival tissue specimens from chronic periodontitis patients, further confirming the biological relevance of A20 in periodontal inflammation. We conclude that TLR9 modulates periodontal disease progression at both the cellular and molecular level and identify A20 as a novel downstream signaling molecule in the course of periodontal inflammation. Understanding the regulation of the TLR9 signaling pathway and the involvement of A20 as a limiting factor of inflammation will uncover alternative therapeutic targets to treat periodontitis and other chronic inflammatory diseases.
Exercise therapy versus arthroscopic partial meniscectomy for degenerative meniscal tear in middle aged patients: randomised controlled trial with two year follow-up
Authors: Kise Nina Jullum , Risberg May Arna , Stensrud Silje , Ranstam Jonas , Engebretsen Lars , Roos Ewa M 
Published: November 2016

ObjectiveTo determine if exercise therapy is superior to arthroscopic partial meniscectomy for knee function in middle aged patients with degenerative meniscal tears.DesignRandomised controlled superiority trial.SettingOrthopaedic departments at two public hospitals and two physiotherapy clinics in Norway.Participants140 adults, mean age 49.5 years (range 35.7–59.9), with degenerative medial meniscal tear verified by magnetic resonance imaging. 96% had no definitive radiographic evidence of osteoarthritis.Interventions12 week supervised exercise therapy alone or arthroscopic partial meniscectomy alone.Main outcome measuresIntention to treat analysis of between group difference in change in knee injury and osteoarthritis outcome score (KOOS4), defined a priori as the mean score for four of five KOOS subscale scores (pain, other symptoms, function in sport and recreation, and knee related quality of life) from baseline to two year follow-up and change in thigh muscle strength from baseline to three months.ResultsNo clinically relevant difference was found between the two groups in change in KOOS4at two years (0.9 points, 95% confidence interval −4.3 to 6.1; P=0.72). At three months, muscle strength had improved in the exercise group (P≤0.004). No serious adverse events occurred in either group during the two year follow-up. 19% of the participants allocated to exercise therapy crossed over to surgery during the two year follow-up, with no additional benefit.ConclusionThe observed difference in treatment effect was minute after two years of follow-up, and the trial's inferential uncertainty was sufficiently small to exclude clinically relevant differences. Exercise therapy showed positive effects over surgery in improving thigh muscle strength, at least in the short term. Our results should encourage clinicians and middle aged patients with degenerative meniscal tear and no definitive radiographic evidence of osteoarthritis to consider supervised exercise therapy as a treatment option.Trial registrationwww.clinicaltrials.gov(NCT01002794).
An introduction to the Emergency Department Adult Clinical Escalation protocol: ED-ACE
Authors: Coughlan Eoin , Geary Una , Wakai Abel , O'Sullivan Ronan , Browne John , McAuliffe Eilish , Ward Marie , McDaid Fiona , Deasy Conor 
Published: November 2016

Purpose of the studyThis study demonstrates how a participatory action research approach was used to address the challenge of the early and effective detection of the deteriorating patient in the ED setting. The approach enabled a systematic approach to patient monitoring and escalation of care to be developed to address the wide-ranging spectrum of undifferentiated presentations and the phases of ED care from triage to patient admission. This paper presents a longitudinal patient monitoring system, which aims to provide monitoring and escalation of care, where necessary, of adult patients from triage to admission to hospital in a manner that is feasible in the unique ED environment.MethodsAn action research approach was taken to designing a longitudinal patient monitoring system appropriate for the ED. While the first draft protocol for post-triage monitoring and escalation was designed by a core research group, six clinical sites were included in iterative cycles of planning, action, reviewing and further planning. Reasons for refining the system at each site were collated and the protocol was adjusted accordingly before commencing the process at the next site.ResultsThe ED Adult Clinical Escalation longitudinal patient monitoring system (ED-ACE) evolved through iterative cycles of design and testing to include: (1) a monitoring chart for adult patients; (2) a standardised approach to the monitoring and reassessment of patients after triage until they are assessed by a clinician; (3) the ISBAR (I=Identify, S=Situation, B=Background, A=Assessment, R=Recommendation) tool for interprofessional communication relating to clinical escalation; (4) a template for prescribing a patient-specific monitoring plan to be used by treating clinicians to guide patient monitoring from the time the patient is assessed until when they leave the ED and (5) a protocol for clinical escalation prompted by single physiological triggers and clinical concern.ConclusionsThis tool offers a link in the ‘Chain of Prevention’ between the Manchester Triage System and ward-based early warning scores taking account of the importance of standardisation, while being sufficiently adaptable for the unique working environment and patient population in the ED.
Excretory Function of Intestinal Tract Enhanced in Kidney Impaired Rats Caused by Adenine
Authors: Yun Yu , Gao Tao , Li Yue , Gao Zhiyi , Duan Jinlian , Yin Hua , Duan Weigang 
Published: November 2016

The main aim of the study was to prove the compensative effect of intestine for renal function. Rat kidney was impaired by intragastrically administrating adenine (400 mg per day for 5 days). Intestinal tract was harvested and equally divided into 20 segments except cecum. Kidneys were harvested and histologically examined with hematoxylin-eosin staining kits. Uric acid, urea (BUN), and creatinine in serum were determined with assay kits, and BUN and creatinine in every intestinal segment were also determined. The results showed that adenine was able to increase uric acid level in serum from

20.98
±
6.98

μg/mL to

40.77
±
7
.
52

μg/mL and cause renal function damage with BUN (from

3.87
±
0.62

mM to 12.

33
±
3.27

mM) and creatinine (from

51.48
±
6.98

μM to

118.25
±
28.63

μM) increasing in serum and with abnormally micromorphological changes in kidney. The amount of BUN and creatinine distributed in intestinal tract was positively correlated with those in blood. In impaired renal function rats, the amount of BUN (from

4.26
±
0.21

μMole to 10.

72
±
0.55

μMole) and creatinine (from

681.4
±
23.3

nMole to

928.7
±
21.3

nMole) distributed in intestinal tract significantly increased. All the results proved that intestinal tract had excretory function compensative for renal function.
Progress and Paradigms in Multiple Myeloma
Authors: Anderson Kenneth C. 
Published: November 2016

Abstract
Remarkable progress has been achieved in multiple myeloma, and patient median survival has been extended 3- to 4-fold. Specifically, there have been 18 newly approved treatments for multiple myeloma in the past 12 years, including seven in 2015, and the treatment paradigm and patient outcome have been transformed. The definition of patients benefitting from these therapies has been broadened. Response criteria now include minimal residual disease (MRD), assessed in bone marrow by multicolor flow cytometry or sequencing, and by imaging for extramedullary disease. Initial therapy for transplant candidates is a triplet incorporating novel therapies—that is, lenalidomide, bortezomib, and dexamethasone or cyclophosphamide, bortezomib, and dexamethasone. Lenalidomide maintenance until progression can prolong progression-free and overall survival in standard-risk multiple myeloma, with incorporation of proteasome inhibitor for high-risk disease. Studies are evaluating the value of early versus late transplant and MRD as a therapeutic goal to inform therapy. In nontransplant patients, triplet therapies are also preferred, with doublet therapy reserved for frail patients, and maintenance as described above. The availability of second-generation proteasome inhibitors (carfilzomib and ixazomib), immunomodulatory drugs (pomalidomide), histone deacetylase inhibitors (panobinostat), and monoclonal antibodies (elotuzumab and daratumumab) allows for effective combination therapies of relapsed disease as well. Finally, novel therapies targeting protein degradation, restoring autologous memory anti–multiple myeloma immunity, and exploiting genetic vulnerabilities show promise to improve patient outcome even further. Clin Cancer Res; 22(22); 5419–27. ©2016 AACR.
See all articles in this CCR Focus section, “Multiple Myeloma: Multiplying Therapies.”
Chromosomal Instability in Cell-Free DNA as a Highly Specific Biomarker for Detection of Ovarian Cancer in Women with Adnexal Masses
Authors: Vanderstichele Adriaan , Busschaert Pieter , Smeets Dominiek , Landolfo Chiara , Van Nieuwenhuysen Els , Leunen Karin , Neven Patrick , Amant Frédéric , Mahner Sven , Braicu Elena Ioana , Zeilinger Robert , Coosemans An , Timmerman Dirk , Lambrechts Diether , Vergote Ignace 
Published: November 2016

Abstract
Purpose: Chromosomal instability is a hallmark of ovarian cancer. Here, we explore copy-number alteration (CNA) profiling in cell-free DNA as a potential biomarker to detect malignancy in patients presenting with an adnexal mass.
Experimental Design: We prospectively enrolled 68 patients with an adnexal mass, of which 57 were diagnosed with invasive or borderline carcinoma and 11 with benign disease. Cell-free DNA was extracted from plasma and analyzed by low-coverage whole-genome sequencing.
Results: Patterns of chromosomal instability were detectable in cell-free DNA using 44 healthy individuals as a reference. Profiles were representative of those observed in matching tumor tissue and contained CNAs enriched in two large datasets of high-grade serous ovarian cancer (HGSOC). Quantitative measures of chromosomal instability, referred to as genome-wide z-scores, were significantly higher in patients with ovarian carcinoma than in healthy individuals or patients with benign disease. Cell-free DNA testing improved malignancy detection (AUC 0.89) over serum CA-125 (AUC 0.78) or the risk of malignancy index (RMI, AUC 0.81). AUC values of cell-free DNA testing even further increased for HGSOC patients specifically (AUC 0.94). At a specificity of 99.6%, a theoretical threshold required for ovarian cancer screening, sensitivity of cell-free DNA testing was 2- to 5-fold higher compared with CA-125 and RMI testing.
Conclusions: This is the first study evaluating the potential of cell-free DNA for the diagnosis of primary ovarian cancer using chromosomal instability as a read-out. We present a promising method to increase specificity of presurgical prediction of malignancy in patients with adnexal masses. Clin Cancer Res; 23(9); 2223–31. ©2016 AACR.