Minutes matter: Time it takes to perform point-of-care ultrasound.

Background: While point-of-care ultrasound (PoCUS) is a safe, versatile tool that can improve patient care, the perceived time investment needed to incorporate PoCUS into clinical care is cited as a barrier to performance. We sought to determine the time it takes to perform a PoCUS examination and whether this time was influenced by training level and prior ultrasound experience. Methods: This was a retrospective study looking at time stamps of all emergency medicine (EM) provider-performed PoCUS examinations during clinical shifts from August 10, 2019, to June 7, 2022, at a suburban academic emergency department that is the site for a 3-year EM residency. Our workflow is order-based; when PoCUS is ordered, that patient's information populates the ultrasound machine worklist. Selecting the patient's name from the worklist generates a time-stamped patient information page (PIP). We defined the PIP time stamp as the start of the PoCUS examination. The duration of one PoCUS examination was defined as the time of the last image acquired minus the time of the PIP. General estimating equations were used to estimate differences between training level and between prior scan status using an exchangeable correlation and Tukey adjusted pairwise comparisons. A two-tailed chi-square analysis was used for comparing accuracy according to training level. Results: Of 4187 PoCUS examinations abstracted, 2144 met study criteria. The median (IQR) time spent per examination was 6.0 (3-9) min. First-year residents took the longest to perform PoCUS among all providers (p < 0.0001). Residents with fewer than 250 prior scans took longer than residents with 501-800 (p = 0.0002) and >800 (p = 0.0013). Resident accuracy was not significantly different according to training level. Conclusions: Overall median time to perform PoCUS was 6.0 min. EM residents became more efficient in performing PoCUS as they advanced from first- to third-year, without compromising accuracy.

Proteomics Identification of Targets for Intervention in Pressure Ulcers.

Pressure ulcers (PUs) are chronic wounds that lead to amputations and death. Little is known about why PUs are recalcitrant to healing. Wound healing is mediated by matrix metalloproteinases (MMPs). The 24 MMPs in humans each exist in three forms, of which only one is catalytically competent. We analyzed human PU samples using an affinity resin that exclusively binds to the catalytically competent MMPs. We identified by mass spectrometry the active forms of MMP-1, MMP-8, MMP-9, and MMP-14. Concentrations of MMP-8, MMP-9, and MMP-14 were higher in human PUs compared to the healthy tissue, whereas those for MMP-1 did not change. Decreasing levels of active MMP-9 as the PU improved argued for a detrimental role for this enzyme. In a mouse model of PUs, a highly selective inhibitor for MMP-9 and MMP-14, (R)-ND-336, accelerated wound closure in parallel with significant amelioration of ulcer stage. (R)-ND-336 holds promise as a first-in-class treatment for PUs.

Selective MMP-9 Inhibitor (R)-ND-336 Alone or in Combination with Linezolid Accelerates Wound Healing in Infected Diabetic Mice.

Diabetic foot ulcers (DFUs) are a common complication of diabetes that are recalcitrant to healing due to persistent inflammation. The majority of DFUs have bacterial biofilms, with Staphylococcus epidermidis as a predominant bacterium, requiring infection control with antibiotics before treatment of the wound. Matrix metalloproteinases (MMPs) play roles in the pathology and repair of DFUs. However, defining the roles of the 24 human MMPs has been challenging due to the presence of three forms for each MMP, of which only one is catalytically competent, and the lack of convenient methods to distinguish among the three forms of MMPs. Using an affinity resin that binds only to the active forms of MMPs, with identification and quantification by mass spectrometry, we found that infected wounds in mice had increased levels of active MMP-9 compared to uninfected ones, paralleling infected human DFUs. MMP-9 activity prevents diabetic wounds from healing. We evaluated the efficacy of the selective small-molecule MMP-9 inhibitor, (R)-ND-336, in the infected diabetic mouse model of wound healing and showed that (R)-ND-336 alone or in combination with the antibiotic linezolid improves wound healing by inhibiting the detrimental MMP-9, mitigating macrophage infiltration to diminish inflammation, and increasing angiogenesis to restore the normal wound healing process. An advantage of this strategy is the ability to administer (R)-ND-336 concurrently with an antibiotic.

Limitations of Knockout Mice and Other Tools in Assessment of the Involvement of Matrix Metalloproteinases in Wound Healing and the Means to Overcome Them.

Matrix metalloproteinases (MMPs) play important roles in wound healing, but attribution of their functions in repair of wounds has been challenging. Commonly used tools such as MMP-knockout mice and zymography often confound analysis, which is complicated further as these enzymes exist in three distinct forms with only one being catalytically competent. With the use of topical exogenously administered recombinant MMP-8 and MMP-13 to diabetic and nondiabetic mouse wounds, we show that these proteinases facilitate wound repair by upregulating IL-6 and increasing neutrophil trafficking with an early onset of inflammation. Furthermore, by spatiotemporal control in the use of a selective MMP-2 inhibitor, along with immunoprecipitation and Western blotting, we provide definitive demonstration that MMP-2 does not affect wound healing, contrary to reports. MMP-2 is found in wounds complexed with TIMPs, which is catalytically incompetent.