Rho-kinase inhibition reduces systolic blood pressure and forearm vascular resistance in healthy older adults: a double-blind, randomized, placebo-controlled pilot study.

Rho-kinase has been implicated in the development of hypertension in preclinical studies and may contribute to age-related blood pressure elevation. This study tested the hypothesis that Rho-kinase contributes to elevated systolic blood pressure (SBP) in healthy older adults. Young (18-30 years, 6F/6M) and older (60-80 years, 7F/6M) adults were enrolled in a double-blind, placebo-controlled crossover study using intravenous fasudil infusion to inhibit Rho-kinase. Fasudil lowered SBP in older adults compared to placebo (saline) (2-h post-infusion: 125 ± 4 vs. 133 ± 4 mmHg, P < 0.05), whereas fasudil had no impact on SBP in young adults. Immediately following fasudil infusion, there was a transient reduction in mean arterial pressure (MAP) in young adults that was no longer evident 1-h post-infusion. In older adults, MAP remained lower throughout the fasudil visit compared to placebo (2-h post-infusion: 93 ± 3 vs. 100 ± 3 mmHg, P < 0.05) such that age-related differences in SBP and MAP were abolished. Aortic stiffness (carotid-femoral pulse wave velocity) was not altered by fasudil when central MAP was included as a covariate in analyses. Fasudil reduced forearm vascular resistance in older (2-h post-infusion: 3.3 ± 0.4 vs. 4.8 ± 0.6 mmHg/ml/min, P < 0.05) but not young (4.0 ± 0.6 vs. 3.8 ± 0.5 mmHg/ml/min) adults, which was accompanied by an increase in brachial artery diameter only in older adults. Brachial artery flow-mediated dilation was not affected by fasudil in either group. These findings indicate that Rho-kinase inhibition reduces SBP in healthy older but not young adults, which is associated with a concomitant reduction in forearm vascular resistance.

Point-of-care Ultrasound Identification of Hepatic Abscess in the Emergency Department.

CASE PRESENTATION: A 92-year-old female with past medical history of hypertension presented to the emergency department with pain in her right shoulder, right flank, and right upper quadrant of her abdomen. Point-of-care ultrasound (POCUS) and computed tomography imaging showed concerns for multiple large hepatic abscesses. Percutaneous drainage removed 240 millileters of purulent fluid that identified Fusobacterium nucleatum, a rare cause of pyogenic liver abscess. DISCUSSION: Emergency physicians should keep hepatic abscess on their differential for right upper quadrant abdominal pain and can use POCUS for expeditious diagnosis.

Nurses' coping strategies during and after an adult in-hospital resuscitation attempt: A scoping study.

AIM: A scoping study was conducted to identify and synthesise literature about nurse coping strategies during and after cardiopulmonary resuscitations (CPRs). BACKGROUND: Nurses frequently engage in CPR events that often lead to patient deaths thereby negatively impacting nurses' mental and physical health compromising patient safety. Little research has been conducted to explore coping strategies nurses use during and after a CPR event. DESIGN: Arksey and O'Malley's framework was used to guide the review process and PRISMA-ScR checklist for reporting the study. METHODS: A comprehensive search (January 1, 1996 - August 1, 2021) using ProQuest, PsychINFO, CINAHL and PubMed databases to locate peer-reviewed publications that met the study's inclusion criteria. We included publications of data collected from nurses who experienced a non-simulated adult CPR event in an acute or critical care hospital setting. Lazarus and Folkman's Ways of Coping Checklist, based on the transactional theory of stress and coping, was used to guide data analysis and categorise and label the coping strategies used by nurses. RESULTS: The search returned 2689 articles, and nine articles comprised the sample after excluding duplicates, titles, abstracts and full-text articles not meeting the inclusion criteria. Nine articles were reviewed to identify the coping strategies used by nurses during and after a CPR event. These strategies were grouped into eight categories. CONCLUSION: When resuscitation was successful, the experience carried little to no stress. The coping strategy most often used during a resuscitation attempt was planful problem solving. The coping strategies used after a failed resuscitation attempt were planful problem solving and seeking social support. Nurses reported that debriefing sessions were not desirable venues for discussing post-resuscitation stress. RELEVANCE TO CLINICAL PRACTICE: The provision of support by employers and colleagues must be intentionally planned and offered to nurses exposed to the stress induced by unsuccessful attempts at CPR.

Plasminogen is a master regulator and a potential drug candidate for the healing of radiation wounds.

Around 95% of cancer patients undergoing radiotherapy experience cutaneous side effects, and some develop radiation wounds or fibrosis. Currently, there is no effective treatment for these indications. We show here that plasminogen administration enhanced the healing of radiation wounds via pleiotropic effects on gene expression. Using RNA sequencing, we found that plasminogen downregulated the expression of genes in the TLR, TNF, WNT, MAPK, and TGF-ß signaling pathways, and enhanced the anti-inflammatory effect of arachidonic acid, leading to significantly decreased inflammation and improved remodeling of granulation tissue compared with placebo treatment. In addition, plasminogen induced metabolic changes, including decreased glycolysis. Importantly, many of the factors downregulated by plasminogen are pro-fibrotic. Therefore, in radiation wounds with excessive inflammation, plasminogen is able to enhance and redirect the healing process, such that it more closely resembles physiological healing with significantly reduced risk for developing fibrosis. This makes plasminogen an attractive drug candidate for the treatment of radiation wounds in cancer patients.

Balancing Deliberate Practice and Reflection: A Randomized Comparison Trial of Instructional Designs for Simulation-Based Training in Cardiopulmonary Resuscitation Skills.

INTRODUCTION: A key question in simulation-based education is how to maximize learning within time and resource limits, including how best to balance hands-on practice versus reflective debriefing. Several instructional design frameworks suggest setting the balance according to the type of learning objective(s); however, broad professional activities such as team-based cardiopulmonary resuscitation include several interrelated component skills. This study experimentally manipulated hands-on practice versus reflective debriefing for cardiopulmonary resuscitation skills, hypothesizing that the former best supports learning taskwork (eg, compression quality), whereas the latter best supports learning teamwork. METHODS: The study was a randomized comparison trial with a pretest and posttest. Twenty-six teams of 5 to 6 first-year residents underwent either "drill" practice of key resuscitation phases, designed to maximize deliberate practice opportunities for individual and team skills, or "scrimmage" practice, designed to maximize full-scenario rehearsals and reflective debriefs. Key taskwork and teamwork behaviors were coded, and compression quality was collected and analyzed from an accelerometer. RESULTS: Most performance parameters improved considerably from a pretest to posttest for both taskwork (eg, percent correct compression depth 62%-81%, P = 0.01) and teamwork (eg, role leadership, 47%-70%, P = 0.00). Only 2 parameters improved differently by condition, favoring "drill" training: checking "Do Not Actively Resuscitate" wristband (odds ratio = 14.75, P = 0.03) and use of compression adjuncts (estimated marginal means = 75% versus 67%, P = 0.03). CONCLUSIONS: Consistent with the notion that component skills in resuscitation do not clearly and exclusively constitute "taskwork" versus "teamwork," both instructional designs led to similar improvements despite differences in the balance between hands-on practice versus reflection.

Plasminogen activation is required for the development of radiation-induced dermatitis.

Skin damage caused by radiation therapy (radiodermatitis) is a severe side effect of radiotherapy in cancer patients, and there is currently a lack of effective strategies to prevent or treat such skin damage. In this work, we show with several lines of evidence that plasminogen, a pro-inflammatory factor, is key for the development of radiodermatitis. After skin irradiation in wild-type (plg+/+) mice, the plasminogen level increased in the irradiated area, leading to severe skin damage such as ulcer formation. However, plasminogen-deficient (plg-/-) mice and mice lacking plasminogen activators were mostly resistant to radiodermatitis. Moreover, treatment with a plasminogen inhibitor, tranexamic acid, decreased radiodermatitis in plg+/+ mice and prevented radiodermatitis in plg+/- mice. Together with studies at the molecular level, we report that plasmin is required for the induction of inflammation after irradiation that leads to radiodermatitis, and we propose that inhibition of plasminogen activation can be a novel treatment strategy to reduce and prevent the occurrence of radiodermatitis in patients.

Radiation schedules in relation to obliteration and complications in hypofractionated conformal stereotactic radiotherapy of arteriovenous malformations.

AIMS: The purpose of this investigation was to assess the obliteration rate and complications following different radiation schedules of hypofractionated conformal stereotactic radiotherapy for cerebral arteriovenous malformations (AVMs). METHODS: Twenty-five patients were treated with 35 Gy in 5 fractions, whereas 31 patients were treated with 30-32.5 Gy (mean: 31.6 +/- 0.23 Gy) in 5 fractions. A complete angiographic follow-up is available for 40 patients. RESULTS: Thirty-seven out of 40 patients (92.5%) have so far shown obliteration of their AVMs after a mean time of 3.2 +/- 0.26 years (range: 2-8 years). The mean AVM volume in these patients was 8.2 +/- 1.0 cm(3) (range: 1.5-29 cm(3)). There was a higher rate of obliteration (88%) in patients treated with 35 Gy compared to those treated with < 35 Gy (78%), even if this was not statistically significant. There was a significantly shorter time to obliteration in patients treated with 35 Gy. All patients who experienced symptomatic radionecrosis belonged to the group treated with 35 Gy. CONCLUSION: A radiation schedule of 35 Gy in 5 fractions may be more effective than a radiation schedule of <35 (30-32.5) Gy in obliterating AVMs. This may, however, be at the price of an increased risk of symptomatic radionecrosis.

Multileaf collimation of electrons--clinical effects on electron energy modulation and mixed beam therapy depending on treatment head design.

The aim of this study was to explore the possibilities of using multileaf-collimated electron beams for advanced radiation therapy with conventional scattering foil flattened beams. Monte Carlo simulations were performed with the aim to improve electron beam characteristics and enable isocentric multileaf collimation. The scattering foil positions, monitor chamber thickness, the MLC location and the amount of He in the treatment head were optimized for three common commercial accelerators. The performance of the three optimized treatment head designs was compared for different SSDs in air, at treatment depth in water and for some clinical cases. The effects of electron/photon beam matching including generalized random and static errors using Gaussian one-dimensional (1 D) error distributions, and also electron energy modulation, were studied at treatment depth in water. The modification of the treatment heads improved the electron beam characteristics and enabled the use of multileaf collimation in isocentric delivery of both electron and photon beams in a mixed beam IMRT procedure.

Comparison between a conventional treatment energy and 50 MV photons for the treatment of lung tumours.

Radiation therapy in the thoracic region is difficult due to the presence of many dose-limiting structures and the large density differences that affect the dose distribution. Conventional irradiation techniques use low-energy photon beams to avoid build-up effects superficially in the tumour and increased lateral scattering of the beams. For deep-seated tumours higher beam energies could have lung-sparing properties that would enable dose escalation. A comparison was made for a conventional low photon energy (6 MV) and 50 MV photons for the treatment of a lung tumour. A representative patient geometry was selected, consisting of a small tumour semi-enclosed in lung tissue. Treatment plans were designed using a commercial 3D-pencil beam treatment planning system. The treatment beams designed in the TPS were simulated with the Monte Carlo code EGS4/BEAM and the dose distribution in the phantom created from the patients CT-data was calculated using MCDOSE with identical beam geometry for both energies. The intrinsic difference between the two photon energies implies a sparing effect of lung that can be utilized for dose escalation. For a treatment with two beams the mean total dose to the tumour could be increased by 5.3% for 50 MV, corresponding to 3.2 Gy for a prescription dose of 60 Gy, with the same complication probability for the treated lung as for 6 MV. In conclusion, high-energy beams have qualities that can be taken advantage of for irradiation of lung tumours. Optimum solutions would probably require the use of both high- and low-energy beams.