Objectives
Cytokine release syndrome (CRS) is a potentially severe complication of COVID-19 most commonly resulting in respiratory failure. This ten-patient study was designed to determine the efficacy of therapeutic plasma exchange (TPE) in improving oxygenation and in reducing the cytokine load in a critically ill subset of patients.
Methods
Five single volume plasma exchanges over eight days within a 14-day study period. In mechanically ventilated patients, oxygenation was measured via the PaO2/FiO2 (P/F) ratio and the oxygenation index (OI) daily for 14 days. Supplemental oxygen requirements were tracked daily for non-ventilated patients.
Results
Non-ventilated patients were liberated from supplemental oxygen after TPE. The response was rapid with an 87% average reduction in oxygenation requirements following and average time to return to room air of 5.25 days. All mechanically ventilated patients demonstrated improvement in oxygenation with a 78% average improvement in the P/F ratio and a 43% improvement in OI. C-reactive protein (CRP) and serum levels of IL-6, IL-8, IL-10, TNFα, IFNγ and GM-CSF, were measured daily with immediate post TPE levels drawn on days 1, 2, 4, 6 and 8. All patients demonstrated significant reductions in CRP, IL-6, IL-10 and TNFα.
Conclusions
In the majority of patients with Penn class 3 and 4 CRS complicating COVID-19, TPE demonstrated a prompt improvement in oxygenation and reduction in cytokine load without compromising patient safety. As this pilot study was envisioned to be hypothesis generating, expanded trials using TPE alone and in conjunction with novel pharmacologic agents are warranted.
Registration
ClinicalTrials.gov
NCT04374149
.
Across diverse critical care topics, propensity score studies published in high-impact journals produced results that were generally consistent with the findings of randomized clinical trials. However, caution is needed when interpreting propensity score studies because occasionally their results contradict those of randomized clinical trials and there is no reliable way to predict disagreements.
Growth of sympatric populations of three important sport fish species: bluegill Lepomis macrochirus, largemouth bass Micropterus salmoides and channel catfish Ictalurus punctatus, in 14 Illinois reservoirs was assessed in an attempt to relate size-specific growth to environmental conditions. Multiple regression relationships for most species and size classes explained a large percentage of the variation in growth. Growth of small bluegill (50 mm total length, L T ) showed a strong negative relationship with bluegill catch per unit effort (cpue), per cent littoral area and pH. Large bluegill (150 mm L T ) growth was negatively related to Daphnia spp. and benthic macroinvertebrate abundance and lake volume, and positively related to bluegill cpue. Growth of small (100 mm L T ) and large (250 mm L T ) largemouth bass was not well explained by any of the measured variables. Growth of both small (300 mm L T ) and large (450 mm L T ) channel catfish was strongly positively related to forage fishes and ichthyoplankton abundance, and per cent littoral area while negatively related to benthic macroinvertebrates. By identifying environmental conditions associated with increased growth rates, these models provide direction for managing fish populations and suggest testable hypotheses for future study of the complex interactions between environmental conditions and growth.
Objectives/Hypothesis
1. To determine the phonation threshold pressure (PTP) and phonation threshold flow (PTF) in excised human larynges. 2. To determine the effects of posterior glottal width, glottal area, and gender on PTP and PTF. 3. To test the hypothesis that hysteresis is present in excised human laryngeal phonation. 4. To compare these results to those from canine experiments and human subject measurements.
Study Design
Induced phonation of excised human larynges in the laboratory.
Methods
Nine human larynges were harvested within 24 hours post-mortem. PTP and PTF at phonation onset and offset were measured on a bench apparatus. The effects of posterior glottal width, glottal area, and gender were examined.
Results
Large inter-subject variability was observed in PTP and PTF. PTP was comparable to those measured in vivo, whereas PTF was substantially higher. One-way ANOVA showed no significant dependence of PTP and PTF on posterior glottal width. Hysteresis was observed, with offset PTP and PTF lower than onset values. Offset measurements had significantly less variability than onset measurements (P = 0.012 for PTP, P = 0.0001 for PTF).
Conclusions
This study is one of the first to report onset and offset PTP and PTF in fresh excised human larynges. The high PTF observed likely reflects a large DC flow component due to vocal fold bowing. Offset PTP and PTF values may be intrinsically more reliably measured than onset values. The large inter-subject variability in PTP and PTF may have implication for the clinical application of these aerodynamic parameters of phonation.
Level of Evidence
N/A (Laboratory study).
Objectives
1. To test whether alteration of the vocal fold medial surface contour can improve phonation. 2. To demonstrate that implant material properties affect vibration even when implant is deep to the vocal fold lamina propria.
Study Design
Induced phonation of excised human larynges.
Methods
Thirteen larynges were harvested within 24 hours post-mortem. Phonation threshold pressure (PTP) and flow (PTF) were measured before and after vocal fold injections using either calcium hydroxylapatite (CaHA) or hyaluronic acid (HA). Small-volume injections (median 0.0625 mL) were targeted to the infero-medial aspect of the thyroarytenoid (TA) muscle. Implant locations were assessed histologically.
Results
The effect of implantation on PTP was material-dependent. CaHA tended to increase PTP, whereas HA tended to decrease PTP (Wilcoxon test P = 0.00013 for onset). In contrast, the effect of implantation on PTF was similar, with both materials tending to decrease PTF (P = 0.16 for onset). Histology confirmed implant presence in the inferior half of the vocal fold vertical thickness.
Conclusions
Taken together, these data suggested the implants may have altered the vocal fold medial surface contour, potentially resulting in a less convergent or more rectangular glottal geometry as a means to improve phonation. An implant with a closer viscoelastic match to vocal fold cover is desirable for this purpose, as material properties can affect vibration even when the implant is not placed within the lamina propria. This result is consistent with theoretical predictions and implies greater need for surgical precision in implant placement and care in material selection.
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