Κυριακή 29 Μαΐου 2022

Plasma trough concentration distribution and safety of high‐dose teicoplanin for patients with augmented renal clearance

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Plasma trough concentration distribution and safety of high-dose teicoplanin for patients with augmented renal clearance

Teicoplanin plasma trough concentration (C min) and probability rates of C min > 10 mg/L in the augmented renal clearance (ARC) and non-ARC groups on the third day of medication (day 3) and during the dose maintenance period. After the HD, plasma samples were collected before the third day of medication. The teicoplanin C min values in the ARC and non-ARC groups were 17.3 ± 9.2 mg/L and 15.5 ± 7.9 mg/L, respectively (p = 0.663) (Figure A). The probability rate of C min > 10 mg/L also did not differ significantly between the two groups (85.7% [6/7] vs. 60.0% [6/10], p = 0.338, Figure C). During the dose maintenance period (3 days after medication), the teicoplanin C min was significantly lower in ARC group than in the non-ARC group (18.3 ± 5.1 mg/L vs. 25.5 ± 11.9 mg/L, p = 0.016, Figure A), while there was no significant difference in the probability rate of C min > 10 mg/L between the two groups (90.0% [9/10] vs. 96.2% [25/26], p = 0.484, Figure C). After the LD, plasma samples were collected before the third day of medication. The teicoplanin C min values in the ARC and non-ARC groups were 6.8 ± 3.9 mg/L and 7.9 ± 3.1 mg/L, respectively (p = 0.585) (Figure B). The probability rate of C min > 10 mg/L did not differ significantly between the two groups (20.0% [1/5] vs. 11.1% [1/9], p = 1.000, Figure D). During the dose maintenance period, the teicoplanin C min values in the ARC and non-ARC groups were 12.2 ± 6.3 mg/L and 13.0 ± 4.6 mg/L, respectively (p = 0.713) (Figure B). The probability rate of C min > 10 mg/L was 61.5% (8/13) in both groups (Figure D). It should be noted that on the third day of medication, the HD group had a significantly higher teicoplanin C min than the LD group for ARC (17.3 ± 9.2 mg/L vs. 6.8 ± 3.9 mg/L, p = 0.039, Figure A and B), but there was no significant intergroup difference in the probability rates of C min > 10 mg/L (85.7% [6/7] vs. 20.0% [1/5], p = 0.072, Figures C and D). During the dose maintenance period, the teicoplanin C min was significantly higher in the HD group than in the LD group for ARC (18.3 ± 5.1 mg/L vs. 12.2 ± 6.3 mg/L, p = 0.022, Figures A and B), while there was no significant intergroup difference in their probability rates of C min > 10 mg/L (90.0% [9/10] vs. 61.5% [8/13], p = 0.179, Figures C and D). Notes: A, HD; B, LD; C, HD; D, LD; *p < 0.05.


Abstract

What Is Known and Objective

There are few reports on the distribution of the plasma trough concentration (C min) of teicoplanin in patients with augmented renal clearance (ARC) and on the safety of a high-dose regimen (HD; 800 mg loading dose for q12h three times followed by an 800 mg qd maintenance dose). The objective of this study was to determine the C min values of teicoplanin in ARC patients using HD teicoplanin to provide a reference for individualized medication.

Methods

Data on patients treated with teicoplanin from January 2019 to January 2021 were collected retrospectively and divided into ARC (creatinine clearance rate [CCr] >130 ml/min, n = 22) and non-ARC (60 ml/min ≤ CCr ≤130 ml/min, n = 24) groups. The C min values in the two patient groups were analysed during the HD and the low-dose regimen (LD; all other regimens) on the third day of medication and during the dose maintenance period. Liver and kidney function indexes were also analysed before and after medication.

Results and Discussions

On the third day of the HD, C min did not differ significantly between the ARC and non-ARC groups (17.3 ± 9.2 mg/L [mean ± SD] vs. 15.5 ± 7.9 mg/L, p = 0.663), while C min in the ARC group was significantly lower for the LD (6.8 ± 3.9 mg/L, p = 0.039). During the dose maintenance period, C min in the ARC group when receiving the HD (18.3 ± 5.1 mg/L) was significantly lower than that in the non-ARC group (25.5 ± 11.9 mg/L, p = 0.016) and significantly higher than that for the LD (12.2 ± 6.3 mg/L, p = 0.022). Nephrotoxicity and hepatotoxicity incidence rates did not differ significantly between these groups.

What Is New and Conclusion

These results suggest that it is necessary to apply a loading dose of 800 mg (but not higher) q12h three times for patients with ARC, with 800 mg needed as a maintenance dose during severe infection, and 600 mg or 400 mg for mild infection.

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Validation of the Augmented Renal Clearance in Trauma Intensive Care scoring system for augmented renal clearance prediction in a trauma subgroup of a mixed ICU population

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Validation of the Augmented Renal Clearance in Trauma Intensive Care scoring system for augmented renal clearance prediction in a trauma subgroup of a mixed ICU population

(Left) ROC curves for ARC detection in trauma subgroup: comparison between ARCTIC score ROC curve and regression ROC curve. AUC, area under the curve; CI, confidence interval. (Right) ROC curves for ARC detection in medical/surgical subgroup: comparison between ARCTIC score ROC curve and regression ROC curve.


Abstract

What is known and Objective

Augmented renal clearance is prevalent in trauma patients and leads to subtherapeutic levels of renally eliminated medications with potentially unfavourable clinical outcomes. The Augmented Renal Clearance of Trauma in Intensive Care (ARCTIC) score has been developed to predict augmented renal clearance in critically ill trauma patients. Our primary objective was to validate this score among the trauma subgroup of a mixed intensive care patient cohort.

Methods

This single-centre, retrospective, observational cohort study assessed augmented renal clearance using a timed 24-h urine collection performed weekly. ARC was defined as a measured creatinine clearance of ≥130 ml/min/1.73 m2. ARCTIC score performance was evaluated through a receiver operator characteristic curves and analysis of sensitivities and specificities for the trauma subgroup, the medical/surgical subgroup and the pooled cohort.

Results and Discussion

Augmented renal clearance was observed in 33.9% (n = 58) of trauma patients (n = 171) and 15.7% (n = 24) of medical/surgical patients (n = 153). Examination of different cutoffs for the ARCTIC score in our trauma population confirmed that the optimal cutoff score was ≥6. Comparison between ROC curves for ARCTIC score and for regression model based upon our data in trauma patients indicated validation of the score in this subgroup. Comparison of sensitivities and specificities for ARCTIC score between trauma (93.1% and 41.6%, respectively) and medical/surgical subjects (87.5% and 49.6%, respectively) showed no clinical nor statistical difference, suggesting validation for the medical/surgical subgroup as well.

What is new and Conclusion

In our mixed ICU population, the ARCTIC score was validated in the trauma subgroup. We also found that the score performed well in the medical/surgical population. Future studies should assess the performance of the ARCTIC score prospectively.

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3D Reconstruction of Phonatory Glottal Shape and Volume: Effects of Neuromuscular Activation

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3D Reconstruction of Phonatory Glottal Shape and Volume: Effects of Neuromuscular Activation

In this study, we utilized a 3D reconstruction approach to visualize the vocal fold medial surface during phonation in an in vivo canine hemilarynx, and we obtained direct measurements of glottal movement, and glottal volume waveform, and resulting voice quality. We present the glottal volume waveform as a correlate of laryngeal vibratory dynamics and highlight the importance of intrinsic laryngeal muscles in modulating medial surface dynamics to achieve improved voice quality.


Introduction

Although phonatory glottal posture and airflow pulse shape affect voice quality, studies to date have been limited by visualization of vocal fold (VF) vibration from a superior view. We performed a 3D reconstruction of VF vibratory motion during phonation from a medial view and assessed the glottal volume waveform and resulting acoustics as a function of neuromuscular stimulation.

Study Design

In vivo canine hemilarynx phonation.

Methods

Across 121 unique combinations of the superior laryngeal nerve (SLN) and recurrent laryngeal nerve (RLN) stimulation, the hemilarynx was excited to the oscillation with airflow. VF medial surface reference points were tracked on high-speed video, mapped into 3D space, and surface shape was restored using cubic spline interpolation. Glottal surface shape, reconstruction-based parameters, and glottal volume waveform were calculated. Fundamental frequency (F0), cepstral peak prominence (CPP), and harmonic amplitude (H1-H2) were measured from high-quality audio samples.

Results

The glottis was convergent during opening and divergent during closing. Neuromuscular activation changed phonatory glottal shape and reduced glottal volume. Significant reduction in glottal volume and closing quotient were present with SLN stimulation. RLN stimulation significantly increased F0 and CPP and decreased H1-H2 (constricted glottis), while SLN effects were similar and synergistic with concurrent RLN stimulation.

Conclusion

3D reconstruction of in vivo medial surface vibration revealed effects of laryngeal nerve stimulation on glottal vibratory pattern and acoustic correlates of voice quality. SLN activation resulted in significantly quicker glottal closure per cycle, decreased glottal volume, and higher-pitched, less breathy, and less noisy voice. RLN had a similar effect on acoustic measures.

Level of Evidence

N/A, Basic Science Laryngoscope, 2022

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Could the Audiometric Criteria for Sudden Sensorineural Hearing Loss Miss Vestibular Schwannomas?

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Could the Audiometric Criteria for Sudden Sensorineural Hearing Loss Miss Vestibular Schwannomas?

Patients with sudden hearing loss whose audiograms did not meet the formal audiometric criteria for sudden sensorineural hearing loss were found to have a similar rate of vestibular schwannoma as those who did. Therefore, we advocate a high index of suspicion of a concomitant vestibular schwannoma with sudden hearing loss of any severity, and urge our colleagues to consider referring those patients to an MRI scan regardless of the hearing loss severity.


Objective

To investigate the likelihood of missing a vestibular schwannoma (VS) diagnosis in patients who present with a sudden hearing loss (SHL) that does not meet the most accepted audiometric criteria for sudden sensorineural hearing loss (SSNHL) (a decrease of ≥30 dB at three consecutive frequencies).

Methods

All adult patients (>18 years) diagnosed with SHL of any severity in a tertiary care referral medical center between 2015 and 2020 and who underwent an MRI scan to rule out VS were included. Statistical analyses were conducted to evaluate the difference between the rate of VS among patients with an initial audiogram, which met the abovementioned criteria, and those who did not. Other audiometric criteria for SNHL were also evaluated (≥10 dB at ≥2 frequencies and ≥ 15 dB at one frequency).

Results

Of the 332 patients included in the study, 152 met the audiometric criteria for SSNHL, and 180 did not. Both groups had a similar VS rate (8.6% vs. 8.9%, p = 0.914). Similar results were found when other audiometric criteria for asymmetric SNHL were analyzed. In a subgroup analysis of patients with VS-associated SSNHL, neither the tumor size nor the Koos classification was associated with any of the audiometric criteria systems.

Conclusion

There should be a high index of suspicion for the presence of VS in patients with an SHL of any severity.

Level of Evidence

3 Laryngoscope, 2022

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Πέμπτη 26 Μαΐου 2022

COVID Salivary diagnostics: a comparative technical study

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ABSTRACT

Since the beginning of the COVID-19 pandemic, molecular diagnostics of SARS-CoV-2 have taken center stage in the detection of infected individuals for isolation purposes but also in the mass surveillance as a preventive strategy to contain the virus spread. While nasopharyngeal swabs (NPS) have remained the golden standard substrate, salivary diagnostic for SARS-CoV-2 has been proposed as an alternative and non-invasive measure in vulnerable individuals. Nevertheless, there is a widespread assumption that salivary RT-PCR does not match the quality of testing using NPS and particular care should be taken in respect to food or beverage intake, when sampling saliva. Our study indicates that without any precaution in the selection of 190 patients, nor restriction over the time-window of sampling, there is 99% match in the COVID-19 positivity between NPS and saliva when using RT-PCR, with a reported Delta in thermal cycles (Cts) values for the viral genes Envelop e (E) and Open reading frame 1ab (Orf1ab) between 0 and 2, a 98.7% Sensitivity and 100% Specificity. This high accuracy is maintained in pooling configurations that can be used for mass-testing purposes in professional and educational settings. The further advantage to using crude saliva as compared to NPS or mouthwash is that direct methods yield robust results. Overall, our study validates and promotes the use of salivary diagnostic for COVID-19 eliminating the need of a medical practitioner for the sampling, resolving the unpleasantness of the NPS intervention and empowering the patient to do self-testing in times of need.

This article is protected by copyright. All rights reserved.

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Septic shock with Chlamydia abortus infection

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Publication date: June 2022

Source: The Lancet Infectious Diseases, Volume 22, Issue 6

Author(s): Mengting Liu, Yin Wen, Hongguang Ding, Hongke Zeng

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12 T high static magnetic field suppresses osteosarcoma cells proliferation by regulating intracellular ROS and iron status

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Publication date: Available online 25 May 2022

Source: Experimental Cell Research

Author(s): Shenghang Wang, Ting Huyan, Chenge Lou, Peng Shang, Hao Zhang

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