Αρχειοθήκη ιστολογίου

Δευτέρα 12 Απριλίου 2021

E. coli GyrA Tower Domain Interacts with QnrB1 Loop B and Plays an Important Role in QnrB1 Protection from Quinolone Inhibition [Mechanisms of Resistance]

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The Qnr pentapeptide repeat proteins interact with DNA gyrase and protect it from quinolone inhibition. The two external loops, particularly the larger loop B, of Qnr proteins are essential for quinolone protection of DNA gyrase. The specific QnrB1 interaction sites on DNA gyrase are not known. In this study, we investigated the interaction between GyrA and QnrB1 using site-specific photo crosslinking of QnrB1 loop B combined with mass spectrometry. We found that amino acid residues 286-298 on the Tower domai n of GyrA interact with QnrB1 and play a key role in QnrB1 protection of gyrase from quinolone inhibition. Alanine replacement of arginine at residue 293 and a small deletion of amino acids 286-289 of GyrA resulted in a decrease in the QnrB1-mediated increase in quinolone MICs and also abolished the QnrB1 protection of purified DNA gyrase from ciprofloxacin inhibition.

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Experience with Liposomal Amphotericin B in Outpatient Parenteral Antimicrobial Therapy (OPAT) [Clinical Therapeutics]

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Background: Outpatient parenteral antimicrobial therapy (OPAT) is a safe, effective, and convenient treatment strategy for patients receiving intravenous antimicrobials in the outpatient setting; however, data is limited describing the use and safety of liposomal amphotericin B (L-AMB).

Methods: Records of patients receiving L-AMB OPAT between 1/1/2015 and 7/31/2018 were retrospectively reviewed. The primary objective was to describe the OPAT patient population discharged on L-AMB and evaluate factors a ssociated with readmission and adverse events (AE). Analysis was performed to evaluate for predictors of worse outcomes.

Results: Forty-two patients (67% male, median age 50 years) were identified, most commonly treated for histoplasmosis. The most common doses of L-AMB were 3 mg/kg (n=16, 38%) or 5 mg/kg (n=14, 33%) based on actual body weight. Twenty-six (62%) patients completed their anticipated course of L-AMB. Twenty-two (52%) patients were readmitted within 30 days of discharge, median time to readmission was 11 days (Interquartile range [IQR] 5-18). While hypokalemia and acute kidney injury (AKI) were common, occurring in 26 (62%) and 20 (48%), respectively, only 5 (12%) were readmitted to the hospital due L-AMB-associated AE. Ninety percent of patients achieved at least partial renal recovery within 30 days after L-AMB discontinuation. Factors significantly associated with AKI include higher L-AMB dose, lower serum potassium levels after therapy initiation, and receipt of potassium supplementation at discharge.

Conclusion: L-AMB is associated with significant AEs; however, these results suggest treatment is feasible in the outpatient setting with close monitoring, as the majority of AEs were managed effectively as an outpatient without long-term sequelae.

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Comparison of In Vitro Susceptibility of Delafloxacin with Ciprofloxacin, Moxifloxacin, and other Comparator Antimicrobials Against Isolates of Nontuberculous Mycobacteria [Susceptibility]

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Nontuberculous mycobacteria (NTM) infections are increasing globally. Mycobacterium avium complex (MAC) and M. abscessus complex are the most commonly reported NTM. Oral treatment options are limited, especially for the M. abscessus. We tested delafloxacin, a new oral fluoroquinolone, against 131 isolates of NTM. Delafloxacin microdilution MICs were performed as recommended by the Clinical and Laboratory Standards Institute using cation adjusted Mueller Hinton broth. The rapidly growing m ycobacteria tested included: M. abscessus subsp. abscessus (16) and subsp. massiliense (5), M. chelonae (11), M. immunogenum (5), M. fortuitum group (13), M. porcinum (7), M. senegalense (7), M. mucogenicum group (5), and M. goodii (1). For the slowly growing NTM (SGM), M. avium (16), M. intracellulare (13), M. chimaera (9), M. arupense (5), M. simiae (5), M. lentiflavum (4), M. kansasii (6), and M. marinum (3) were tested. Delafloxacin was most active in vitro against M. fortuitum and M. mucogenicum groups and M. kansasii with MIC50 values of 0.12-0.5 μg/mL (MIC range 0.001-4 μg/mL) compared to ≤0.06->4 μg/mL for ciprofloxacin and ≤0.06->8 μg/mL for moxifloxacin. For other SGM (including MAC), and the M. abscessus/chelonae, the delafloxacin MIC range was 8->16 μg/mL compared to ciprofloxacin and moxifloxacin of 0.5->4 μg/mL and ≤0.06-8 μg/mL, respectively. To our knowledge, this is the first MIC study with delafloxacin to use Clinical and Laboratory Standards Institute (CLSI) recommended methods. This study illustrates the potential utility of delafloxacin in treatment of infections due to some NTM.

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In Vitro and In Vivo Antifungal Activity of AmBisome Compared to Conventional Amphotericin B and Fluconazole against Candida auris [Susceptibility]

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Antifungal activity of AmBisome against Candida auris was determined in vitro and in vivo. AmBisome showed MIC50 and MIC90 values of 1 and 2 μg/mL, respectively. Unlike conventional amphotericin B, significant in vivo efficacy was observed in the AmBisome 7.5 mg/kg -treated group in survival and reduction of kidney tissue fungal burden compared to the untreated group. Our data shows that AmBisome shows significant antifungal activity against C. auris < i>in vitro as well as in vivo.

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Falls Predict Acute Hospitalization in Parkinson's Disease

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J Parkinsons Dis. 2021 Apr 7. doi: 10.3233/JPD-212539. Online ahead of print.

ABSTRACT

BACKGROUND: There is a need for identifying risk factors for hospitalization in Parkinson's disease (PD) and also interventions to reduce acute hospital admission.

OBJECTIVE: To analyze the frequency, causes, and predictors of acute hospitalization (AH) in PD patients from a Spanish cohort.

METHODS: PD patients recruited from 35 centers of Spain from the COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015) cohort from January 2016 to November 2017, were included in the study. In order to identify predictors of AH, Kaplan-Meier estimates of factors considered as potential predictors were obtained and Cox regression performed on time to hospital encounter 1-year after the baseline visit.

RESULTS: Thirty-five out of 605 (5.8%) PD patients (62.5±8.9 years old; 59.8% males) presented an AH during the 1-year follow-up afte r the baseline visit. Traumatic falls represented the most frequent cause of admission, being 23.7% of all acute hospitalizations. To suffer from motor fluctuations (HR [hazard ratio] 2.461; 95% CI, 1.065-5.678; p = 0.035), a very severe non-motor symptoms burden (HR [hazard ratio] 2.828; 95% CI, 1.319-6.063; p = 0.008), falls (HR 3.966; 95% CI 1.757-8.470; p = 0.001), and dysphagia (HR 2.356; 95% CI 1.124-4.941; p = 0.023) was associated with AH after adjustment to age, gender, disease duration, levodopa equivalent daily dose, total number of non-antiparkinsonian drugs, and UPDRS-IIIOFF. Of the previous variables, only falls (HR 2.998; 95% CI 1.080-8.322; p = 0.035) was an independent predictor of AH.

CONCLUSION: Falls is an independent predictor of AH in PD patients.

PMID:33843696 | DOI:10.3233/JPD-212539

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Outcomes after cervical vertebral interbody fusion using an interbody fusion device and polyaxial pedicle screw and rod construct in 10 horses (2015-2019)

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Equine Vet J. 2021 Apr 12. doi: 10.1111/evj.13449. Online ahead of print.

ABSTRACT

BACKGROUND: Further development of surgical techniques for equine cervical stabilisation is necessary to make the procedure less technically demanding, reduce complications, and improve outcomes.

OBJECTIVE: To describe clinical outcomes and owner reports in horses undergoing placement of an interbody fusion device and polyaxial pedicle screw and rod construct for cervical vertebral fusion in horses with cervical vertebral compressive myelopathy.

STUDY DESIGN: Retrospective case series.

METHODS: Data were retrieved from medical records of 10 horses undergoing cervical vertebral fusion (2015-2019). Records were evaluated for signalment, duration of clinical signs, number and location of compression sites, grade of ataxia, duration of hospitalisation, and complications. Long-term follow-up was obtained through clinical re-evaluation, postoperativ e radiographs, and owner contact.

RESULTS: Breeds were mixed. Median age was 24 (range 12-168) months. There were 2/10 mares, 4/10 geldings, and 4/10 stallions. Preoperative grade of ataxia ranged from 1-3/5. Fusion was performed at one (n=3) or two (n=7) sites. Two horses were euthanised within the first year. In 6 out of 8 horses with ≥1-year follow-up, ataxia improved by 1 - 3 grades, with an average improvement of 1.25 grades. In four horses, ataxia improved to grade 0-1. In two horses the gait was unaffected, but neck comfort improved. Complications included seroma formation (n=9), pain (n=5), fever (n=4), upper respiratory tract obstruction (n=2), azotemia (n=2), screw breakage (n=2), progression of neurological signs (n=1), Horner's Syndrome (n=1), dysphagia (n=1), hives (n=1), implant infection (n=1), and nondisplaced fracture (n=1).

MAIN LIMITATIONS: Small case series, heterogeneous patient population.

CONCLUSIONS: This technique resulted in ≥1 grade g ait improvement in 6/10 cases operated and 6/8 cases for which ≥1-year follow-up was available, similar to other methods. Fatal complications related to implant placement did not occur. This technique may represent a safer alternative to current techniques of ventral interbody fusion with similar outcomes.

PMID:33844334 | DOI:10.1111/evj.13449

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Lingual Exercise

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J Speech Lang Hear Res. 2021 Apr 12:1-13. doi: 10.1044/2021_JSLHR-20-00461. Online ahead of print.

ABSTRACT

Purpose Adherence is a concern in dysphagia management. Poor adherence with recommendations can negatively affect treatment efficacy and patient outcomes. For exercise-based therapies, low adherence can alter the dose of exercise delivered to the muscle, which can diminish impact of exercise. It has been established that low adherence is a problem in dysphagia treatments; however, relationships among levels of adherence and outcomes from exercise-based interventions have not been explored. Method In this retrospective pilot study, data were collected from a multicenter clinical demonstration program in the Veterans Affairs hospital system to examine the relationships between patient adherence with a device-facilitated lingual exercise regimen. Outcomes were compared pre- and posttreatment using a paired t test or Wilcoxon matched -pairs signed-ranks test, and relationships among adherence and outcome measures were evaluated using Pearson or Spearman rank correlation coefficients, as appropriate. Results Patient adherence was evenly distributed across participants: Adherence at the front sensor was 59.3% (SD = 28.2), ranging from 5.5% to 95.8%; the back sensor adherence was 55.9% (SD = 29.8), ranging from 1.1% to 97.2%. Maximum isometric pressure (MIP) generation, at both the front and back sensors, was increased from pre- to posttreatment (p < .0001, front; p = .008, back). Functional Oral Intake Scale (FOIS) scores were also significantly improved at the posttreatment time point as compared to baseline (p = .005). However, there were no significant correlations among adherence and outcome measures (front sensor adherence vs. ΔMIP, r = -.161, p = .342; back sensor adherence vs. ΔMIP, r = .002, p = .991; front sensor adherence vs. ΔFOIS, r = -.183, p = .279; back sensor adherence vs. ΔFOIS, r = -.160, p = .399). Conclusions These findings suggest that patient adherence with this lingual exercise program was not related to the increases in lingual pressure generation or improvement in functional oral intake observed in this cohort. These preliminary findings suggest the need for future, prospective, controlled, and randomized clinical trials to further investigate patient adherence with a lingual exercise program and related impacts of adherence on exercise dose and swallowing-related outcomes.

PMID:33844587 | DOI:10.1044/2021_JSLHR-20-00461

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Κυριακή 11 Απριλίου 2021

Massive Burns after Forge Explosion: New Technique to Protect Perineal Skin Grafts Without A Diverting Ostomy

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The Small 14-French (Fr) Percutaneous Catheter vs. Large (28-32Fr) Open Chest Tube for Traumatic Hemothorax (P-CAT): A Multi-center Randomized Clinical Trial

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Introduction The traditional treatment of traumatic hemothorax (HTX) has been an insertion of a large-bore 36-40 French (FR) chest tube (CT). Our previous single-center randomized controlled trial (RCT) had shown that 14Fr percutaneous catheters (PCs) (pigtail) were equally as effective as CTs. We performed a multi-center RCT, hypothesizing that PCs are as equally effective as CTs in the management of patients with traumatic HTX. (NCT03546764) Methods We performed a multi-institution prospective RCT comparing 14Fr PCs to 28-32Fr CTs in the management of patients with traumatic HTX from July, 2015 to September, 2020. We excluded patients who were in extremis and required emergent tube placement, and those who refused to participate. The primary outcome was failure rate, defined as a retained HTX requiring a second intervention. Secondary outcomes included daily drainage output, tube days, intensive care unit and hospital length of stay, and insertion perception experience (IPE) score on a scale of 1 to 5 (1=tolerable experience, 5=worst experience). Unpaired Student's t-test, chi-square and Wilcoxon rank-sum test was utilized with significance set at P
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Four-Factor Prothrombin Complex Concentrate in Adjunct to Whole Blood in Trauma-Related Hemorrhage: Does Whole Blood Replace the Need for Factors?

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Background The use of whole blood (WB) for the treatment of hemorrhagic shock and coagulopathy is increasing in civilian trauma patients. Four-factor prothrombin complex concentrate (4-PCC) in adjunct to component therapy showed improved outcomes in trauma patients. Our study aims to evaluate the outcomes of trauma patients who received 4-PCC+WB compared to WB alone. Methods We performed a three-year (2015-2017) analysis of the American College of Surgeons-Trauma Quality Improvement Program database. All adult (age ≥18 years) trauma patients who received WB were included. We excluded patients who were on preinjury anticoagulants. Patients were stratified into two groups: 4-PCC+WB versus WB alone, and matched in a 1:2 ratio using propensity score matching. Outcome measures were packed red blood cells, plasma, platelets, and cryoprecipitate transfused, in-hospital complications, hospital and ICU length of stay (LOS) among survivors, and mortality. Results A total of 252 patients (4-PCC+WB, 84; WB alone, 168) were matched. Mean age was 47±21 years; 63% were males; median injury severity score was 30 [21–40], and 87% had blunt injuries. Patients who received 4-PCC+WB had decreased requirement for pRBC (8 units vs. 10 units; p=0.04) and FFP (6 units vs. 8 units; p=0.01) transfusion, lower rates of acute kidney injury (p=0.03), and ICU LOS (5 days vs. 8 days, p=0.01) compared to WB alone. There was no difference in the platelet transfusion (p=0.19), cryoprecipitate transfusion (p=0.37), hospital LOS (p=0.72), and in-hospital mortality (p=0.72) between the two groups. Conclusion Our study demonstrates that the use of 4-PCC as an adjunct to WB is associated with a reduction in transfusion requirements and ICU LOS compared to WB alone in the resuscitation of trauma patients. Further studies are required to evaluate the role of PCC with WB in the resuscitation of trauma patients. Level of Evidence Level III Therapeutic Oral Podium Presentation: 34th EAST Annual Scientific Assembly that will be held virtually on January 13-14, 2021 There are no identifiable conflicts of interest to report. The authors have no financial or proprietary interest in the subject matter or materials discussed in the manuscript. Address for correspondence: Bellal Joseph, MD, FACS, University of Arizona, Department of Surgery Division of Trauma, Critical Care, And Emergency Surgery, 1501 N. Campbell Ave, Room 5411, P.O. Box 245063, Tucson, AZ 85724 Email: bjoseph@surgery.arizona.edu Tel: 520-626-5056 Fax: 520-626-5016 © 2021 Lippincott Williams & Wilkins, Inc.
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How We Do It: C-V Transposition Flap for Reconstruction of the Nipple–Areolar Complex After Mohs Surgery

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