Gender Disparity in Authorship Among Orthopaedic Surgery Residents.

Background: Gender disparity remains pervasive in orthopaedic surgery, which affects the research pursuits of orthopaedic surgeons. The purpose of this study was to characterize gender-related authorship trends of orthopaedic surgery residents, including evaluation of gender-concordant publication rates. Methods: An observational cross-sectional analysis of US orthopaedic surgery residency programs was performed. Information on residency programs and demographics of each cohort was collected. Publication metrics consisting of number of first and non-first author publications and H-indices were manually obtained for PGY-3 to PGY-5 residents attending the 25 programs ranked the highest for research output by Doximity. Gender of each resident and senior author was determined from institutional websites using photos, biographies, and preferred pronouns when available. Results: A total of 532 residents, 169 (31.8%) female and 363 (68.2%) male, were included for authorship analysis. Of them, 415 (78%) had at least one first author publication, which did not vary significantly by gender. Female residents had disproportionately fewer first author publications compared with their representation (22% vs. 31.8%, p < 0.00001). Female residents averaged fewer first and non-first author publications compared with male residents (2.8 vs. 4.6, p = 0.0003; 6.4 vs. 10, p = 0.0001 respectively). Despite fewer publications overall, a greater subset of publications by female residents were written in collaboration with a female senior author compared with publications by male residents (p < 0.0001). Male residents had a higher average H-index of 5.4 vs. 3.9 among female residents (p = 0.00007). Conclusion: Despite similar rates of first author publication among male and female residents, female residents had fewer publications overall, lower H-indices, and disproportionately fewer first author publications than would be expected given their representation. Findings from this study suggest that gender disparity in orthopaedic surgery extends to differences in research productivity as early as in residency. This may have negative implications on the career advancement of female orthopaedic surgeons. Additional work is needed to identify and understand biases in research productivity and career advancement, to promote more equitable strategies for academic achievement. Level of Evidence: IV.

Biologic Adjuvants to Rotator Cuff Repairs Induce Anti-inflammatory Macrophage 2 Polarization and Reduce Inflammatory Macrophage 1 Polarization In Vitro.

PURPOSE: To examine the effect of various biologic adjuvants on the polarization of macrophages in an in vitro model for rotator cuff tears. METHODS: Tissue was harvested from 6 patients undergoing arthroscopic rotator cuff repair. An in vitro model of the supraspinatus and subacromial bursa was created and treated with control, platelet-rich plasma (PRP), autologous activated serum (AAS), or a combination of PRP+AAS. The effect of treatment on macrophage polarization between M1 proinflammatory macrophages or M2 anti-inflammatory macrophages was measured using gene expression, protein expression, flow cytometry, and nitric oxide production. RESULTS: Tendon and bursa treated with PRP, AAS, and PRP+AAS significantly decreased the gene expression of M1 markers interleukin (IL)-12 and tumor necrosis factor-alpha while significantly increasing the expression of M2 markers arginase, IL-10, and transforming growth factor-ß (P < .05) compared with treatment with control. Enzyme-linked immunosorbent assay analysis of protein production demonstrated that, compared with control, coculture treated with PRP, AAS, and PRP+AAS significantly decreased markers of M1-macrophages (IL-6, IL-12, and tumor necrosis factor-alpha) while significantly increasing the expression of markers of M2-macrophages (arginase, IL-10, and transforming growth factor-beta) (P < .05). Flow cytometry analysis of surface markers demonstrated that compared with control, tendon and bursa treated with PRP, AAS, and PRP+AAS significantly decreased markers of M1-macrophages (CD80, CD86, CD64, CD16) while significantly increasing the expression of markers of M2-macrophages (CD163 and CD206) (P < .05). Treatment of the coculture with PRP, AAS, and PRP+AAS consistently demonstrated a decrease in nitric oxide production (P < .05) compared with control. AAS and PRP+AAS demonstrated an increased macrophage shift to M2 compared with PRP alone, whereas there was not as uniform of a shift when comparing PRP+AAS with AAS alone. CONCLUSIONS: In an in vitro model of rotator cuff tears, the treatment of supraspinatus tendon and subacromial bursa with PRP, AAS, and PRP+AAS demonstrated an increase in markers of anti-inflammatory M2-macrophages and a concomitant decrease in markers of proinflammatory M1-macrophages. AAS and PRP+AAS contributed to a large shift to macrophage polarization to the anti-inflammatory M2 compared with PRP. CLINICAL RELEVANCE: The mechanism of biologic adjuvant effects on the rotator cuff remains poorly understood. This study suggests that they may contribute to polarization of macrophages for their proinflammatory (M1) state to the anti-inflammatory (M2) state.

Angiographic Coronary Slow Flow Is Not a Valid Surrogate for Invasively Diagnosed Coronary Microvascular Dysfunction.

BACKGROUND: Ischemia with no obstructive coronary arteries is frequently caused by coronary microvascular dysfunction (CMD). Consensus diagnostic criteria for CMD include baseline angiographic slow flow by corrected TIMI (Thrombolysis In Myocardial Infarction) frame count (cTFC), but correlations between slow flow and CMD measured by invasive coronary function testing (CFT) are uncertain. OBJECTIVES: The aim of this study was to investigate relationships between cTFC and invasive CFT for CMD. METHODS: Adults with ischemia with no obstructive coronary arteries underwent invasive CFT with thermodilution-derived baseline coronary blood flow, coronary flow reserve (CFR), and index of microcirculatory resistance (IMR). CMD was defined as abnormal CFR (<2.5) and/or abnormal IMR (≥25). cTFC was measured from baseline angiography; slow flow was defined as cTFC >25. Correlations between cTFC and baseline coronary flow and between CFR and IMR and associations between slow flow and invasive measures of CMD were evaluated, adjusted for covariates. All patients provided consent. RESULTS: Among 508 adults, 49% had coronary slow flow. Patients with slow flow were more likely to have abnormal IMR (36% vs 26%; P = 0.019) but less likely to have abnormal CFR (28% vs 42%; P = 0.001), with no difference in CMD (46% vs 51%). cTFC was weakly correlated with baseline coronary blood flow (r = -0.35; 95% CI: -0.42 to -0.27), CFR (r = 0.20; 95% CI: 0.12 to 0.28), and IMR (r = 0.16; 95% CI: 0.07-0.24). In multivariable models, slow flow was associated with lower odds of abnormal CFR (adjusted OR: 0.53; 95% CI: 0.35 to 0.80). CONCLUSIONS: Coronary slow flow was weakly associated with results of invasive CFT and should not be used as a surrogate for the invasive diagnosis of CMD.

Chikungunya virus infection disrupts lymph node lymphatic endothelial cell composition and function via MARCO.

Infection with chikungunya virus (CHIKV) causes disruption of draining lymph node (dLN) organization, including paracortical relocalization of B cells, loss of the B cell-T cell border, and lymphocyte depletion that is associated with infiltration of the LN with inflammatory myeloid cells. Here, we found that, during the first 24 hours of infection, CHIKV RNA accumulated in MARCO-expressing lymphatic endothelial cells (LECs) in both the floor and medullary LN sinuses. The accumulation of viral RNA in the LN was associated with a switch to an antiviral and inflammatory gene expression program across LN stromal cells, and this inflammatory response - including recruitment of myeloid cells to the LN - was accelerated by CHIKV-MARCO interactions. As CHIKV infection progressed, both floor and medullary LECs diminished in number, suggesting further functional impairment of the LN by infection. Consistent with this idea, antigen acquisition by LECs, a key function of LN LECs during infection and immunization, was reduced during pathogenic CHIKV infection.

Human Rotator Cuff Tears Reveal an Age-Dependent Increase in Markers of Cellular Senescence and Selective Removal of Senescent Cells With Dasatinib + Quercetin Increases Genetic Expression of COL1A1 In Vitro.

PURPOSE: To quantify cellular senescence in supraspinatus tendon and subacromial bursa of humans with rotator cuff tears and to investigate the in vitro efficacy of the senolytic dasatinib + quercetin (D+Q) to eliminate senescent cells and alter tenogenic differentiation. METHODS: Tissue was harvested from 41 patients (mean age, 62 years) undergoing arthroscopic rotator cuff repairs. In part 1 (n = 35), senescence was quantified using immunohistochemistry and gene expression for senescent cell markers (p16 and p21) and the senescence-associated secretory phenotype (SASP) (interleukin [IL] 6, IL-8, matrix metalloproteinase [MMP] 3, monocyte chemoattractant protein [MCP] 1). Senescence was compared between patients <60 and ≥60 years old. In part 2 (n = 6) , an in vitro model of rotator cuff tears was treated with D+Q or control. D+Q, a chemotherapeutic and plant flavanol, respectively, kill senescent cells. Gene expression analysis assessed the ability of D+Q to kill senescent cells and alter markers of tenogenic differentiation. RESULTS: Part 1 revealed an age-dependent significant increase in the relative expression of p21, IL-6, and IL-8 in tendon and p21, p16, IL-6, IL-8, and MMP-3 in bursa (P < .05). A significant increase was seen in immunohistochemical staining of bursa p21 (P = .028). In part 2, D+Q significantly decreased expression of p21, IL-6, and IL-8 in tendon and p21 and IL-8 in bursa (P < .05). Enzyme-linked immunosorbent assay analysis showed decreased release of the SASP (IL-6, MMP-3, MCP-1; P = .002, P = .024, P < .001, respectively). Tendon (P = .022) and bursa (P = .027) treated with D+Q increased the expression of COL1A1. CONCLUSIONS: While there was an age-dependent increase in markers of cellular senescence, this relationship was not consistently seen across all markers and tissues. Dasatinib + quercetin had moderate efficacy in decreasing senescence in these tissues and increasing COL1A1 expression. CLINICAL RELEVANCE: This study reveals that cellular senescence may be a therapeutic target to alter the biological aging of rotator cuffs and identifies D+Q as a potential therapy.

The female self-advocacy in Cancer Survivorship scale is a psychometrically sound measure of self-advocacy in male cancer survivors.

OBJECTIVE: To develop and psychometrically evaluate an adapted version of the Female Self-Advocacy in Cancer Survivorship (FSACS) Scale in men with a history of cancer. METHODS: This psychometric instrument development and validation study used a two-phase approach to first adapt the FSACS Scale items to reflect the experience of men with a history of cancer and then evaluate the psychometric properties of the adapted scale compared to the original FSACS Scale. The study was conducted from December 2018 through April 2022 through cancer clinics, patient registries, and national advocacy organizations. We evaluated scale reliability and validity using reliability coefficients, exploratory and confirmatory factor analyses, and item analyses to determine a final set of scale items. RESULTS: Item responses from N = 171 men with a history of cancer were evaluated to determine scale validity. After removing poor-performing items based on item-level analyses, factor analyses confirmed that a 3-factor structure of both the adapted and original FSACS Scale best fit the scale. The 10 new items did not outperform the original 20-item scale and were therefore excluded from the final scale. The final 20-item scale explained 87.94% of item variance and subscale's Cronbach α varied from 0.65 to 0.86. CONCLUSION: The SACS Scale can be used in research and clinical contexts to assess the propensity of men and women to get their needs, values, and priorities met in the face of a challenge.

The effect of augmenting suture material with magnesium and platelet-rich plasma on the in vitro adhesion and proliferation potential of subacromial bursa-derived progenitor cells.

Background: Connective tissue subacromial bursa-derived progenitor cells (SBDCs) have been suggested as a potent biologic augment to promote healing of the repaired rotator cuff tendon. Maximizing the amount of retained progenitor cells at the tendon repair site is essential for ensuring an optimal healing environment, warranting a search for proadhesive and proliferative adjuvants. The purpose was to evaluate the effect of magnesium (Mg), platelet-rich plasma (PRP), and a combination of both adjuvants on the in vitro cellular adhesion and proliferation potential of SBDCs on suture material commonly used in rotator cuff surgery. Methods: SBDCs were isolated from subacromial bursa samples harvested during rotator cuff repair and cultured in growth media. Commercially available collagen-coated nonabsorbable flat-braided suture was cut into 1-inch pieces, placed into 48-well culture dishes, and sterilized under ultraviolet light. Either a one-time dose of 5 mM sterile Mg, 0.2 mL of PRP, or a combination of both adjuvants was added, while a group without treatment served as a negative control. Cellular proliferation and adhesion assays on suture material were performed for each treatment condition. Results: Augmenting the suture with Mg resulted in a significantly increased cellular adhesion (total number of attached cells) of SBDCs compared to PRP alone (31,527 ± 19,884 vs. 13,619 ± 8808; P < .001), no treatment (31,527 ± 19,884 vs. 21,643 ± 8194; P = .016), and combination of both adjuvants (31,527 ± 19,884 vs. 17,121 ± 11,935; P < .001). Further, augmentation with Mg achieved a significant increase in cellular proliferation (absorbance) of SBDCs on suture material when compared to the PRP (0.516 ± 0.207 vs. 0.424 ± 0.131; P = .001) and no treatment (0.516 ± 0.207 vs. 0.383 ± 0.094; P < .001) group. The combination of Mg and PRP showed a significantly higher proliferation potential compared to PRP alone (0.512 ± 0.194 vs. 0.424 ± 0.131; P = .001) and no treatment (0.512 ± 0.194 vs. 0.383 ± 0.094; P < .001). There were no significant differences in the remaining intergroup comparisons (P > .05, respectively). Conclusion: Augmenting suture material with Mg resulted in a significantly increased cellular adhesion of SBDCs compared to untreated suture material, as well as augmentation with PRP alone or a combination of both adjuvants. Further, Mg with or without PRP augmentation achieved a significant increase in the cellular proliferation of SBDCs on suture material compared to untreated sutures and augmentation with PRP alone. Application of Mg may be a clinically feasible approach to optimizing the use of SBDCs as a biological augment in rotator cuff repair, while combined augmentation with PRP may harness the full potential for optimized tissue recovery due to the high concentration of PRP-derived growth factors.

Inclusion of functional measures and frailty in the development and evaluation of medicines for older adults.

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E7, the guidance for the conduct of clinical trials in people older than age 65 years, dates from 1994. Since then, the inclusion of older people in clinical trials has hardly improved, particularly for the oldest old age group (individuals older than age 75 years), which is the fastest growing demographic bracket in the EU. Even though most medications are taken by this group, relevant endpoints and safety outcomes for this cohort are rarely included and reported, both in clinical trials and regulatory approval documents. To improve the critical appraisal and the regulatory review of medicines taken by frail older adults, eight recommendations are presented and discussed in this Health Policy. These recommendations are brought together from different perspectives and experience of the treatment of older patients. On one side, the perspective of medical practitioners from various clinical disciplines, with their direct experience of clinical decision making; on the other, the perspective of regulators assessing the data submitted in medicine registration dossiers, their relevance to the risk-benefit balance for older patients, and the communication of the findings in the product information. Efforts to improve the participation of older people in clinical trials have been in place for more than a decade, with little success. The recommendations presented here are relevant for stakeholders, authorities, pharmaceutical companies, and researchers alike, as the implementation of these measures is not under the capacity of a single entity. Improving the inclusion of frail older adults requires awareness, focus, and action on the part of those who can effect a much needed change.

A Randomized Controlled Trial of Precision Nutrition Counseling for Service Members at Risk for Metabolic Syndrome.

INTRODUCTION: Metabolic syndrome (MetS) is a threat to the active component military as it impacts health, readiness, retention, and cost to the Military Health System. The most prevalent risk factors documented in service members' health records are high blood pressure (BP), low high-density lipoprotein cholesterol, and elevated triglycerides. Other risk factors include abdominal obesity and elevated fasting blood glucose. Precision nutrition counseling and wellness software applications have demonstrated positive results for weight management when coupled with high levels of participant engagement and motivation. MATERIALS AND METHODS: In this prospective randomized controlled trial, trained registered dietitians conducted nutrition counseling using results of targeted sequencing, biomarkers, and expert recommendations to reduce the risk for MetS. Upon randomization, the treatment arm initiated six weekly sessions and the control arm received educational pamphlets. An eHealth application captured diet and physical activity. Anthropometrics and BP were measured at baseline, 6 weeks, and 12 weeks, and biomarkers were measured at baseline and 12 weeks. The primary outcome was a change in weight at 12 weeks. Statistical analysis included descriptive statistics and t-tests or analysis of variance with significance set at P < .05. RESULTS: Overall, 138 subjects enrolled from November 2019 to February 2021 between two military bases; 107 completed the study. Demographics were as follows: 66% male, mean age 31 years, 66% married, and 49% Caucasian and non-Hispanic. Weight loss was not significant between groups or sites at 12 weeks. Overall, 27% of subjects met the diagnostic criteria for MetS on enrollment and 17.8% upon study completion. High deleterious variant prevalence was identified for genes with single-nucleotide polymorphisms linked to obesity (40%), cholesterol (38%), and BP (58%). Overall, 65% of subjects had low 25(OH)D upon enrollment; 45% remained insufficient at study completion. eHealth app had low adherence yet sufficient correlation with a valid reference. CONCLUSIONS: Early signs of progress with weight loss at 6 weeks were not sustained at 12 weeks. DNA-based nutrition counseling was not efficacious for weight loss.

Injury and Treatment Characteristics of Middle School-Aged Patients Under the Care of Athletic Trainers from 2010-2022: A Report from the Athletic Training Practice-Based Research Network.

CONTEXT: Exploring sports-related musculoskeletal injuries and treatment characteristics in middle school sports may help inform patient care decisions such as appropriate medical coverage. OBJECTIVE: To describe injury and treatment characteristics of middle school-aged athletes receiving care from athletic trainers within the Athletic Training Practice-Based Research Network (AT-PBRN). DESIGN: Descriptive study. SETTING: Middle school. PATIENT OR OTHER PARTICIPANTS: Middle school-aged athletes (n=1,011; male=503, female=506) with sports-related musculoskeletal injuries. MAIN OUTCOME MEASURE(S): Electronic patient records were analyzed from the AT-PBRN from 59 athletic trainers across 14 states between 2010-2022. Summary statistics (frequency, percentages, median, interquartile ranges [IQR]) were used to describe injury (age at injury, sex, sport, body part, diagnosis) and treatment characteristics (type of treatment, number of visits, number of procedures per visit). RESULTS: Football (17.7%, n=179), basketball (17.6%, n=178), and soccer (14.9%, n=151) reported the highest number of injuries. Ankle (17.2%, n=174), knee (16.5%, n=167), and head (14.1%, n=143) were the most common injury locations. Concussion (13.0%, n=131), ankle strain/sprain (12.4%, n=125), and thigh/hip/groin sprain/strain (11.1%, n=112) were the most reported diagnoses. Therapeutic exercise or activities (25.6%, n=1068), athletic trainer evaluation or re-evaluation (22.9%, n=957) and hot/cold packs (18.4%, n=766) were the most common services with a median of 2 visits (IQR=1-4) and 2 procedures (IQR=1-2) per visit. CONCLUSIONS: Football, basketball, and soccer reported the most musculoskeletal injuries for middle school-aged athletes. Concussions were the most frequent diagnosis, followed by ankle sprains/strains. Our findings are similar to prior investigations at high school and collegiate levels. Treatments at the middle school level were also similar to those that have been previously reported at the high school level with therapeutic exercise/activity, athletic trainer evaluation or re-evaluation, and hot/cold packs being the most common treatments. This information may be useful for informing patient care decisions at the middle-school level.

Chikungunya virus infection disrupts lymph node lymphatic endothelial cell composition and function via MARCO.

Infection with chikungunya virus (CHIKV) causes disruption of draining lymph node (dLN) organization, including paracortical relocalization of B cells, loss of the B cell-T cell border, and lymphocyte depletion that is associated with infiltration of the LN with inflammatory myeloid cells. Here, we find that during the first 24 h of infection, CHIKV RNA accumulates in MARCO-expressing lymphatic endothelial cells (LECs) in both the floor and medullary LN sinuses. The accumulation of viral RNA in the LN was associated with a switch to an antiviral and inflammatory gene expression program across LN stromal cells, and this inflammatory response, including recruitment of myeloid cells to the LN, was accelerated by CHIKV-MARCO interactions. As CHIKV infection progressed, both floor and medullary LECs diminished in number, suggesting further functional impairment of the LN by infection. Consistent with this idea, we find that antigen acquisition by LECs, a key function of LN LECs during infection and immunization, was reduced during pathogenic CHIKV infection.

A realist process evaluation of an intervention to promote competencies in interprofessional collaboration among interdisciplinary integrated care teams for older people: Study protocol.

Background: International policy is increasingly committed to placing interdisciplinary team-working at the centre of health and social care integration across the lifespan. The National Clinical Programme for Older People in Ireland has a critical role in the design and implementation of the National Older Person's Service Model, which aims to shift the delivery of care away from acute hospitals towards community-based care. Interdisciplinary Community Specialist Teams for older persons (CST-OPs) play an important role in this service model. To support the development of competencies for interprofessional collaboration and an interdisciplinary team-based approach to care integration, a culture shift will be required within care delivery. Design:This study builds upon a collaborative partnership project which co-designed a framework describing core competencies for interprofessional collaboration in CST-OPs. A realist-informed process evaluation of the framework will be undertaken as the competencies described in the framework are being fostered in newly developed CST-OPs under the national scale-up of the service model. Realist evaluation approaches reveal what worked, why it worked (or did not), for whom and under what circumstances. Three iterative and integrated work packages are proposed which combine multiple methods of data collection, analysis and synthesis. Prospective data collection will be undertaken within four CST-OPs, including qualitative exploration of the care experiences of older people and family carers. Discussion: The realist explanatory theory will provide an understanding of how interprofessional collaboration can be fostered and sustained in various contexts of care integration for older people. It will underpin curriculum development for team-based education and training of health and social care professionals, a key priority area in the national Irish health strategy. It will provide healthcare leaders with knowledge of the resources and supports required to harness the benefits of interprofessional collaboration and to realise the goals of integrated care for older people.

The relationships between acetylcholine-induced chest pain, objective measures of coronary vascular function and symptom status.

Background: Acetylcholine-induced chest pain is routinely measured during the assessment of microvascular function. Aims: The aim was to determine the relationships between acetylcholine-induced chest pain and both symptom burden and objective measures of vascular function. Methods: In patients with angina but no obstructive coronary artery disease, invasive studies determined the presence or absence of chest pain during both acetylcholine and adenosine infusion. Thermodilution-derived coronary blood flow (CBF) and index of microvascular resistance (IMR) was determined at rest and during both acetylcholine and adenosine infusion. Patients with epicardial spasm (>90%) were excluded; vasoconstriction between 20% and 90% was considered endothelial dysfunction. Results: Eighty-seven patients met the inclusion criteria. Of these 52 patients (60%) experienced chest pain during acetylcholine while 35 (40%) did not. Those with acetylcholine-induced chest pain demonstrated: (1) Increased CBF at rest (1.6 ± 0.7 vs. 1.2 ± 0.4, p = 0.004) (2) Decreased IMR with acetylcholine (acetylcholine-IMR = 29.7 ± 16.3 vs. 40.4 ± 17.1, p = 0.004), (3) Equivalent IMR following adenosine (Adenosine-IMR: 21.1 ± 10.7 vs. 21.8 ± 8.2, p = 0.76), (4) Increased adenosine-induced chest pain (40/52 = 77% vs. 7/35 = 20%, p < 0.0001), (5) Increased chest pain during exercise testing (30/46 = 63% vs. 4/29 = 12%, p < 0.00001) with no differences in exercise duration or electrocardiographic changes, and (6) Increased prevalence of epicardial endothelial dysfunction (33/52 = 63% vs. 14/35 = 40%, p = 0.03). Conclusions: After excluding epicardial spasm, acetylcholine-induced chest pain is associated with increased pain during exercise and adenosine infusion, increased coronary blood flow at rest, decreased microvascular resistance in response to acetylcholine and increased prevalence of epicardial endothelial dysfunction. These findings raise questions about the mechanisms underlying acetylcholine-induced chest pain.

Development of a Joint Professional Practice Model for the Total Nursing Force of the United States Military: Describing an Evidence-Based Process Across Multiple Entities.

Professional practice models are a hallmark of professional organizations. Creating a model that can apply across contexts, however, can be a challenge. This article describes the process that a team of nurse leaders and researchers used to create a professional practice model that would serve active-duty and civilian nurses working in military treatment facilities.

Local Complement Contributes to Pathogenic Activation of Lung Endothelial Cells in SARS-CoV-2 Infection.

Endothelial dysfunction and inflammation contribute to the vascular pathology of coronavirus disease (COVID-19). However, emerging evidence does not support direct infection of endothelial or other vascular wall cells, and thus inflammation may be better explained as a secondary response to epithelial cell infection. In this study, we sought to determine whether lung endothelial or other resident vascular cells are susceptible to productive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and how local complement activation contributes to endothelial dysfunction and inflammation in response to hypoxia and SARS-CoV-2-infected lung alveolar epithelial cells. We found that ACE2 (angiotensin-converting enzyme 2) and TMPRSS2 (transmembrane serine protease 2) mRNA expression in lung vascular cells, including primary human lung microvascular endothelial cells (HLMVECs), pericytes, smooth muscle cells, and fibroblasts, was 20- to 90-fold lower compared with primary human alveolar epithelial type II cells. Consistently, we found that HLMVECs and other resident vascular cells were not susceptible to productive SARS-CoV-2 infection under either normoxic or hypoxic conditions. However, viral uptake without replication (abortive infection) was observed in HLMVECs when exposed to conditioned medium from SARS-CoV-2-infected human ACE2 stably transfected A549 epithelial cells. Furthermore, we demonstrated that exposure of HLMVECs to conditioned medium from SARS-CoV-2-infected human ACE2 stably transfected A549 epithelial cells and hypoxia resulted in upregulation of inflammatory factors such as ICAM-1 (intercellular adhesion molecule 1), VCAM-1 (vascular cell adhesion molecule 1), and IL-6 (interleukin 6) as well as complement components such as C3 (complement C3), C3AR1 (complement C3a receptor 1), C1QA (complement C1q A chain), and CFB (complement factor B). Taken together, our data support a model in which lung endothelial and vascular dysfunction during COVID-19 involves the activation of complement and inflammatory signaling and does not involve productive viral infection of endothelial cells.

Findings from the development of a nursing joint professional practice model for the U.S. military.

BACKGROUND: By 2022 the Defense Health Agency became responsible for administration of all military treatment facilities (MTFs), which were previously managed by their respective military services. However, three different service-specific nursing professional practice models currently govern nursing practice in MTFs. PURPOSE: To describe the literature search, review, and synthesis of evidence which informed the JPPM and provide some of the most actionable findings. METHODS: A team of tri-service nurses developed the JPPM by conducting six rigorous systematic reviews to synthesize evidence pertaining to relevant model components. DISCUSSION: A total of 51,360 titles and abstracts were initially screened. Data were extracted from 540 included articles. The team then developed standards for five JPPM components: evidence-based practice, safety and quality, leadership development, healthy work environment, and operational readiness. CONCLUSION: The JPPM is a meaningful framework that will help create a mutual professional identity and shared vision to promote a unified nursing force in U.S. military settings.

Performance-Based Assessment of Trauma Systems: Estimates for the State of Ohio.

OBJECTIVES: There are no widely accepted metrics to determine the optimal number and geographic distribution of trauma centers (TCs). We propose a Performance-based Assessment of Trauma System (PBATS) model to optimize the number and distribution of TCs in a region using key performance metrics. METHODS: The proposed PBATS approach relies on well-established mathematical programming approach to minimize the number of level I (LI) and level II (LII) TCs required in a region, constrained by prespecified system-related under-triage (srUT) and over-triage (srOT) rates and TC volume. To illustrate PBATS, we collected 6002 matched (linked) records from the 2012 Ohio Trauma and EMS registries. The PBATS-suggested network was compared to the 2012 Ohio network and also to the configuration proposed by the Needs-Based Assessment of Trauma System (NBATS) tool. RESULTS: For this data, PBATS suggested 14 LI/II TCs with a slightly different geographic distribution compared to the 2012 network with 21 LI and LII TC, for the same srUT≈.2 and srOT≈.52. To achieve UT ≤ .05, PBATS suggested 23 LI/II TCs with a significantly different distribution. The NBATS suggested fewer TCs (12 LI/II) than the Ohio 2012 network. CONCLUSION: The PBATS approach can generate a geographically optimized network of TCs to achieve prespecified performance characteristics such as srUT rate, srOT rate, and TC volume. Such a solution may provide a useful data-driven standard, which can be used to drive incremental system changes and guide policy decisions.

Components, Implementation, and Outcomes of a Nursing Professional Practice Model: A Systematic Review.

Nursing professional practice models (PPMs) are known to have beneficial effects on nurse and patient outcomes. Determining what components should be present in a PPM, how to implement a PPM, and evaluating the outcomes associated with a PPM is less certain. Therefore, as part of a larger project to develop a nursing PPM for use within the United States Military Health System, this study aimed to conduct a systematic literature review on nursing PPMs. Specifically, the review sought to investigate components, implementation, and outcomes of PPMs in current literature. A total of 37 articles were included in the review. The literature supported the development of 12 recommendations for creating, implementing, and evaluating a nursing PPM. As health care facilities develop their own PPMs or reassess their current PPMs, findings from this review may assist hospital leadership by providing the most recent evidence on the strategic value of nursing PPMs in contemporary health care.