A Quality Improvement Project to Increase Compliance With a Facility Protocol on Surgical Antimicrobial Prophylaxis.

Surgical site infections (SSIs) contribute to negative outcomes for patients and health care organizations. Compliance with clinical practice guidelines likely can help prevent SSIs. An interdisciplinary team at a regional referral center in Michigan sought to reduce SSIs by improving compliance with the facility's preoperative antibiotic selection, dosing, timing, and redosing protocol. The interventions for the quality improvement project included adding the preprocedural antibiotics and doses to the master OR schedule; holding an education session for all preoperative nurses, intraoperative nurses, and anesthesia professionals; and posting a reference guide in the preoperative and intraoperative areas. Compliance with the facility's protocol for antibiotic selection, dosing, and timing significantly improved. However, SSI rates and compliance with redosing recommendations did not change significantly. The team decided to add the antibiotic order information to the master OR schedule permanently. The team plans to consider providing education sessions on administering preprocedural antibiotics outside the OR.

Repeated immunization with ATRA-containing liposomal adjuvant transdifferentiates Th17 cells to a Tr1-like phenotype.

In many autoimmune diseases, autoantigen-specific Th17 cells play a pivotal role in disease pathogenesis. Th17 cells can transdifferentiate into other T cell subsets in inflammatory conditions, however, there have been no attempts to target Th17 cell plasticity using vaccines. We investigated if autoantigen-specific Th17 cells could be specifically targeted using a therapeutic vaccine approach, where antigen was formulated in all-trans retinoic acid (ATRA)-containing liposomes, permitting co-delivery of antigen and ATRA to the same target cell. Whilst ATRA was previously found to broadly reduce Th17 responses, we found that antigen formulated in ATRA-containing cationic liposomes only inhibited Th17 cells in an antigen-specific manner and not when combined with an irrelevant antigen. Furthermore, this approach shifted existing Th17 cells away from IL-17A expression and transcriptomic analysis of sorted Th17 lineage cells from IL-17 fate reporter mice revealed a shift of antigen-specific Th17 cells to exTh17 cells, expressing functional markers associated with T cell regulation and tolerance. In the experimental autoimmune encephalomyelitis (EAE) mouse model of MS, vaccination with myelin-specific (MOG) antigen in ATRA-containing liposomes reduced Th17 responses and alleviated disease. This highlights the potential of therapeutic vaccination for changing the phenotype of existing Th17 cells in the context of immune mediated diseases.

Gamma Oscillations and Potassium Channel Modulation in Schizophrenia: Targeting GABAergic Dysfunction.

Impairments in gamma-aminobutyric acid (GABAergic) interneuron function lead to gamma power abnormalities and are thought to underlie symptoms in people with schizophrenia. Voltage-gated potassium 3.1 (Kv3.1) and 3.2 (Kv3.2) channels on GABAergic interneurons are critical to the generation of gamma oscillations suggesting that targeting Kv3.1/3.2 could augment GABAergic function and modulate gamma oscillation generation. Here, we studied the effect of a novel potassium Kv3.1/3.2 channel modulator, AUT00206, on resting state frontal gamma power in people with schizophrenia. We found a significant positive correlation between frontal resting gamma (35-45 Hz) power (n = 22, r = 0.613, P < .002) and positive and negative syndrome scale (PANSS) positive symptom severity. We also found a significant reduction in frontal gamma power (t13 = 3.635, P = .003) from baseline in patients who received AUT00206. This provides initial evidence that the Kv3.1/3.2 potassium channel modulator, AUT00206, may address gamma oscillation abnormalities in schizophrenia.

Patient-Reported Outcome Measures: How to Maximize Their Utility and Mitigate Health Care Disparities.

Patient-reported outcome measures (PROMs) provide a standardized assessment from the patient about their own health status. Although originally developed as research tools, PROMs can be used in clinical orthopaedic care to complement objective functional measures (eg, range of motion). When PROMs are used during clinical care, they can improve patient outcomes, engagement, well-being, and patient-physician communication. Therefore, PROMs are increasingly integrated into shared decision-making approaches to guide treatment decisions, enhance treatment plans, and predict outcomes. They are also being used in quality measurement and value-based health care arrangements. However, methods to communicate PROMs with patients have not been fully developed, and there continue to be barriers to implementing their collection and communication at scale. In addition, measuring care quality and communicating PROMs with patients may have unintended consequences, such as when used in measurement without accounting for confounding factors (eg, psychological and social health), or in perpetuating health care disparities when used imprecisely (eg, lack of linguistic or cultural validation). It is important to describe the current state of PROM use in orthopaedic surgery, highlight opportunities and challenges of PROM use in clinical care, and provide a roadmap for how to incorporate PROMs to equitably improve patient health and build orthopaedic surgery practices.

Evaluating medical students' knowledge of patient-reported outcomes and the impact of curriculum intervention in consecutive cohorts.

BACKGROUND: Patient-reported outcomes (PROs) collection and utilization improves patient-provider communication, symptom reporting, and patient satisfaction. Despite their significance, the science and utility of PROs are not part of required curriculum in medical education. The authors describe the results of a survey distributed to medical students evaluating their experience, knowledge, and perceptions of PROs, report on outcomes of the impact of formal PRO education on medical student knowledge, and describe strategies to foster the spread of PRO education into other programs. METHODS: The authors developed and distributed a 20-question web-based survey distributed to medical students at two U.S. medical schools to evaluate students' experience, knowledge, and perceptions of PROs. To compare medical students' knowledge in their pre-clinical years (M1-M2) to those in their clinical years (M3-M4), the authors calculated odds ratios and determined significance determined using chi-squared tests. To determine the utility of formal education on medical students' knowledge of PROs, the authors invited 4th year medical students at a single institution to participate in a survey before and two weeks after receiving formal PRO education as part of the medical school curriculum, spanning three years. RESULTS: 137 (15%) medical students responded to the initial survey. Respondents' knowledge of PROs was low and did not differ when comparing pre-clinical to clinical years in school. Less than 10% had received education on PROs and only 16% felt prepared to use PROs in patient care. Respondents demonstrated positive attitudes towards PROs, with 84% expressing interest in learning about PROs. In the second phase education cohort of 231 (77% response rate) 4th -year medical students over three years, formal education improved correct response rates to PRO questions. After education, 90% (121/134) agreed PROs are an important component of high-quality care. CONCLUSIONS: This study identifies a gap in knowledge about PROs among medical students irrespective of year in training. It also shows that structured education may help fill the PRO knowledge gap, potentially providing future clinicians with the skills to implement PROs into clinical practice, aligning with the broader shift towards patient-centric evidence-based healthcare practices.

Chemical profiling by UHPLC-Q-TOF-HRESI-MS/MS and antibacterial properties of Entada abyssinica (Fabaceae) constituents.

A rapid untargeted UHPLC-Q-TOF-ESI-MS/MS-Based metabolomic profiling of the medicinal plant Entada abyssinica was performed. A total of 18 metabolites were detected, of which 10 could not be identified. Based on this result, an extensive chemical investigation of the CH2Cl2-MeOH (1:1) extract of this plant was carried out, leading to the isolation of a new ceramide, named entadamide (1), together with nine known compounds: monomethyl kolavate (2), 24-hydroxytormentic acid (3) chondrillasterol (4), 3-O-ß-D glucopyranosylstigmasterol (5), 3-O-ß-D glucopyranosylsitosterol (6), quercetin 3'-methylether (7), 2,3-dihydroxypropyl icosanoate (8), 2,3-dihydroxy-propyl 23-hydroxytricosanoate (9) and 2,3-dihydroxy-propyl 24-hydroxytetracosanoate (10). Their structures were elucidated by the analyses of their spectroscopic and spectrometric data (1D and 2D NMR, and HRESI-MS) in comparison with those reported in the literature. Furthermore, the crude extract and some isolated compounds were tested against non-ciprofloxacin resistant strains viz, Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922), Samonella thyphi (ATCC 19430) and Samonella enterica (NR4294). The tested samples demonstrated significant activity against all the tested bacteria (MIC values: 3.12-12.5 µg/mL).

Impact of Sports Participation on Achievement of Clinically Relevant Outcomes 2 Years After ACL Reconstruction.

Background: Clinically relevant threshold values associated with patient-reported outcome measures after orthopaedic procedures such as anterior cruciate ligament reconstruction (ACLR) are important for relating these scores to meaningful postoperative improvement. Purpose/Hypothesis: The purpose of this study was to determine the Patient Acceptable Symptom State (PASS) for the Patient-Reported Outcomes Measurement Information System Computer Adaptive Test (PROMIS-CAT) after ACLR. It was hypothesized that preoperative sport participation would have an impact on PASS achievement. Study Design: Case series; Level of evidence, 4. Methods: Included were consecutive patients who underwent primary assisted ACLR between January 4 and August 1, 2016. Patients were administered the PROMIS-CAT Physical Function (PF) and Pain Interference domains preoperatively and at a minimum 2 years postoperatively, with external anchor questions used to determine the PASS. Receiver operating characteristic (ROC) curves were constructed for the entire study population as well as separately for athletes and nonathletes to determine PROMIS PASS thresholds for each population. A previously published PROMIS-PF minimal clinically important difference was used to evaluate postoperative improvement. A post hoc multivariate nominal logistic multivariate analysis was constructed to assess the effects of preoperative patient characteristics on the likelihood of attaining both the minimal clinically important difference and PASS. Results: In total, 112 patients were included in the study, with 79 (71%) having recreational or higher levels of athletic participation. The PASS for the study population was 56.0 (area under the ROC curve, 0.86) and was unaffected by baseline PROMIS-PF scores but was affected by preoperative athletic participation (56.0 for athletes, 49.0 for nonathletes). A post hoc analysis found 57 patients (51%) achieved the PASS for the PROMIS-PF (cutoff, 56.0), but when the athlete and nonathlete thresholds were applied to their respective patient groups, 66% of athletes and 64% of nonathletes achieved the PASS postoperatively. The multivariate analysis found that sport participation (odds ratio, 6.2; P = .001) but not age, sex, body mass index, or preoperative PROMIS affected the likelihood of achieving the PASS on the PROMIS-PF. Conclusion: Preoperative athletic participation significantly affected the ability to achieve PASS.

Practice Variations in Managing Infantile Hemangiomas.

Infantile hemangioma (IH) is the most common benign tumor of infancy. For children with IH who require treatment, propranolol and other beta blockers have been shown to be safe and effective. Although consensus guidelines for managing IH have been published, anecdotal experience suggests that there remain variations in management. This study was performed to document these variations amongst providers and to identify areas for future research. We conducted an Internet-based survey of clinicians who treat patients with IH. Hypothetical cases and management scenarios were presented. Twenty-nine respondents participated in the survey. Most respondents use generic propranolol in infants with growing IH of the head and neck, with a goal dose of 2 mg/kg/d, until ~1 year of age. A variety of management strategies were documented including which patients should be treated, optimal dose and duration of therapy, how patients should be monitored, which patients should get additional workup, how propranolol should best be discontinued, and how often to see patients in follow-up. This study demonstrates wide practice variations in managing patients with IH. Further research is indicated to address these variations and develop additional/updated evidence-based guidelines.

Republication of "Current Concepts Review: Hallux Rigidus".

Arthritis of the first metatarsophalangeal (MTP) joint, hallux rigid, is a common and disabling source of foot pain in the adult population. Hallux rigidus is characterized by diseased cartilage and large, periarticular osteophytes that result in a stiff, painful joint. Activity modification, sensible shoes, orthotics, anti-inflammatory medications and occasional intra-articular steroid injections can be attempted to alleviate the discomfort associated with hallux rigidus. A number of surgical options exist for the treatment of recalcitrant hallux rigidus. Cheilectomy is a useful treatment for dorsal impingement pain seen in mild hallux rigidus. A new polyvinyl alcohol hemi-arthroplasty implant has shown promising early and midterm results in the treatment of advanced hallux rigidus; however, arthrodesis of the first MTP joint remains the gold standard treatment for advanced hallux rigidus because of unpredictable outcomes after early-generation joint replacement implants.

The Role of Autopsy in Quality Assurance: Pilot Study of a Method for Prospective Reporting of Diagnostic Errors Discovered at Autopsy.

ABSTRACT: Hospital autopsies frequently reveal errors in diagnosis that could have affected the patient's clinical outcome. The aims of this study were (1) to investigate the ability of autopsy at our institution to elucidate unrecognized antemortem diagnoses and (2) to pilot a method for tabulating diagnostic discrepancies on a prospective basis. The study sample consisted of 296 cases from our hybrid hospital/forensic autopsy service during the period 2016 to 2018. Discrepancies in autopsy and clinical diagnosis were reported by pathologists at the time of autopsy report generation using a standard form. The rates of major discrepancies between autopsy and clinical diagnoses were 37.5% for in-hospital cases and 25% for patients who died outside our hospital (P < 0.05). The most common discrepant category was infection. The overall rates of discrepant causes of death were 14% (in hospital) and 8% (out of hospital) (ns). Overall percentages of cases with major diagnostic discrepancies were higher in our study than have been previously reported. It is possible that the nature of our patient population plays a role in this result. This study describes an important prospective reporting tool that will allow us to track rates of medical errors and improve diagnosis and treatment of the critically ill.

Necrotizing plasma cell-rich aortitis and sudden cardiac death: Late sequelae of COVID-19?

The ongoing epidemic caused by the coronavirus SARS-CoV-2 is characterized by a variety of pathologic processes within the syndrome of COVID-19. Usually beginning as an upper respiratory infection with potential progression to a pneumonitis, many cases of COVID-19 that show minimal signs or symptoms initially may develop adverse systemic sequelae later, such as widespread thrombo-embolic phenomena, systemic inflammatory disorders (especially in children), or vasculitis. Here, we present a patient who suffered a sudden cardiac death following persistent SARS-CoV-2 viral positivity for four-and-one-half months after a mild clinical viral course. At routine autopsy, a remarkable plasma cell-rich necrotizing aortitis was uncovered. The aortic intima displayed diffuse, circumferential ongoing chronic intimal edema, inflammation, and neo-vascularization. The plasma cell-rich inflammatory process also involved the origin of the left main coronary artery (LM) causing a coronary arteritis accompanied by subacute, stenosing intimal vascular smooth muscle cell (VSMC) proliferation resulting in acute myocardial necrosis as a cause of death. A similar vasculitis and plaque were noted during the routine autopsy at the ostium of the celiac artery; vasculitis was not found systemically or in smaller caliber vessels. Through a variety of techniques including extensive histopathologic and immunohistochemical characterization, immunostaining localization of viral antigen, and transmission electron microscopy we present highly suggestive evidence that this unique necrotizing, plasma cell-rich aortitis is a rare sequela of COVID-19.

Operationalizing PROMs at the Musculoskeletal Practice and Policy Levels.

There continues to be growing interest in patient-reported outcome measures (PROMs), especially as value-based healthcare initiatives gain more traction. Although it is well-established that PROMs can be useful in clinical research, how to operationalize PROMs in clinical care and policy initiatives remains a "work in progress." Following the design of a comprehensive PROM administration and routine collection system, orthopaedic surgeons and their patients can reap the benefits of PROMs in practice through improved shared clinical decision-making discussions at the individual patient level and closer symptom monitoring on a large scale, with improved resource allocation at the population health level. Although certain government and payer incentives exist to collect PROMs at present, it is reasonable to assume that future policy initiatives will begin to use the actual PROM scores to assess clinical outcomes. Orthopaedic surgeons with interest in this area should prioritize their involvement in policy discussion to ensure PROMs are being used appropriately in novel payment models and policy endeavors so that they are both evaluated and compensated fairly. Specifically, orthopaedic surgeons can help ensure appropriate risk adjustment of patients when this is being done. Undoubtedly, PROMs will only become a larger part of musculoskeletal care moving forward.

Both-Column Acetabular Fractures: Does Surgical Approach Vary Based on Using Virtual 3D Reconstructions?

Displacement of the anterior and posterior column complicates decision making for both-column acetabular fractures. We questioned whether pelvic surgeons agree on treatment strategy, and whether the use of virtual 3D reconstructions changes the treatment strategy of choice. A nationwide cross-sectional survey was performed in all pelvic trauma centers in the Netherlands. Twenty surgeons assessed 15 both-column fractures in 2D as well as 3D. Based on conventional imaging, surgical treatment was recommended in 89% of cases, and by adding 3D reconstructions this was 93% (p = 0.09). Surgical approach was recommended as anterior (65%), posterior (8%) or combined (27%) (poor level of agreement, κ = 0.05) based on conventional imaging. The approach changed in 37% (p = 0.006), with most changes between a combined and anterior approach (still poor level of agreement, κ = 0.13) by adding 3D reconstructions. Additionally, surgeons' level of confidence increased from good in 38% to good in 50% of cases. In conclusion, surgeons do not agree on the treatment strategy for both-column acetabular fractures. Additional information given by 3D reconstructions may change the chosen surgical approach and increase surgeons' confidence about their treatment decision. Therefore, virtual 3D reconstructions are helpful for assessing both-column fracture patterns and aid in the choice of treatment strategy.

AOA Critical Issues: Patient-Reported Outcome Measures: Why Every Orthopaedic Practice Should Be Collecting Them.

ABSTRACT: Patient-centered care is essential to providing high-quality value-based care. Patient-reported outcome measures (PROMs) are arguably the best tools available to orthopaedic providers for providing patient-centered care. Many clinical opportunities exist for the implementation of PROMs into routine practice, such as shared decision-making, mental health screening, and prediction of postoperative disposition. Routine use of PROMs is also an adjunct to the streamlining of documentation, patient intake, and telemedicine visits, and hospitals can aggregate PROMs for the purpose of risk stratification. Physicians can harness the power of PROMs for quality improvement initiatives and improvement of the patient experience. Despite these numerous applications, PROMs are frequently underutilized tools. Understanding the many benefits of PROMs may allow orthopaedic practices to justify investing in these valuable tools.

Does Patient-Reported Outcome Measures Use at New Foot and Ankle Patient Clinic Visits Improve Patient Activation, Experience, and Satisfaction?

BACKGROUND: Patient-reported outcome measures (PROMs) can help predict clinical outcomes and improve shared clinical decision-making discussions. There remains a paucity of research assessing how the use of PROMs may drive improved patient experience and patient activation. METHODS: New foot and ankle patients completed PROMIS physical function (PF), pain interference (PI), and depression assessments. Patients were then randomized to viewing and discussing their PROMIS scores with their surgeon or not. Following the clinic visit, patients completed a series of Clinician & Group Survey-Consumer Assessment of Healthcare Providers and Systems (CG-CAHPS) questions and the Patient Activation Measure (PAM). Responses to the CG-CAHPS questions and PAM were compared between the 2 groups and after clustering on surgeon. Potential interaction effects by social deprivation were also explored. RESULTS: After enrolling patients but removing those lost to follow-up or with missing data, 97 and 116 patients remained in the intervention control cohorts, respectively. No difference was found in CG-CAHPS responses nor PAM scores between the 2 groups (P > .05). All surgeons were highly rated by all patients. When clustered by surgeon, intervention subjects were less likely to indicate "top box" scores for the understanding domain of the CG-CAHPS question (OR 0.51, P < .001) and had decreased odds of high patient activation compared to control subjects (OR 0.67; P = .005). Among the most socially disadvantaged patients, there was no difference in control and intervention subjects in their likelihood of having high patient activation (P = .09). CONCLUSION: Highly rated foot and ankle surgeons who show and discuss PROM results may not improve patient experience or activation and may, in fact, decrease understanding or patient activation in select populations. Future work is needed to determine when PROM discussions are most beneficial and how best to present PROMs data, as we suspect that how the information was presented-and not the use of PROMs-resulted in our findings. Health literacy tools and/or communication training may better engage different patient groups regarding PROMs. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Inflammasome inhibition protects dopaminergic neurons from α-synuclein pathology in a model of progressive Parkinson's disease.

Neuroinflammation has been suggested as a pathogenetic mechanism contributing to Parkinson's disease (PD). However, anti-inflammatory treatment strategies have not yet been established as a therapeutic option for PD patients. We have used a human α-synuclein mouse model of progressive PD to examine the anti-inflammatory and neuroprotective effects of inflammasome inhibition on dopaminergic (DA) neurons in the substantia nigra (SN). As the NLRP3 (NOD-, LRR- and pyrin domain-containing 3)-inflammasome is a core interface for both adaptive and innate inflammation and is also highly druggable, we investigated the implications of its inhibition. Repeat administration of MCC950, an inhibitor of NLRP3, in a PD model with ongoing pathology reduced CD4+ and CD8+ T cell infiltration into the SN. Furthermore, the anti-inflammasome treatment mitigated microglial activation and modified the aggregation of α-synuclein protein in DA neurons. MCC950-treated mice showed significantly less neurodegeneration of DA neurons and a reduction in PD-related motor behavior. In summary, early inflammasome inhibition can reduce neuroinflammation and prevent DA cell death in an α-synuclein mouse model for progressive PD.

Clinical Improvement Following Operative Management of Ankle Fractures Among Patients With and Without Moderate to High Depressive Symptoms: An Analysis Using PROMIS.

Background: Understanding the recovery trajectory following operative management of ankle fractures can help surgeons guide patient expectations. Further, it is beneficial to consider the impact of mental health on the recovery trajectory. Our study aimed to address the paucity of literature focused on understanding the recovery trajectory following surgery for ankle fractures, including in patients with depressive symptoms. Methods: From February 2015 to March 2020, patients with isolated ankle fractures were asked to complete Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF), Pain Interference (PI), and Depression questionnaires as part of routine care at presentation and follow-up time points. Linear mixed effects regression models were used to evaluate the patient recovery pattern, comparing the preoperative time point to <3 months, 3-6 months, and >6 months across all patients. Additional models that included the presence of depression symptoms as a covariate were then used. Results: A total of 153 patients met inclusion criteria. By 3-6 months, PROMIS PF (ß: 9.95, 95% CI: 7.97-11.94, P < .001), PI (ß: -10.30, 95% CI: -11.87 to -8.72, P < .001), and Depression (ß: -5.60, 95% CI: -7.01 to -4.20, P < .001) improved relative to the preoperative time point. This level of recovery was sustained thereafter. When incorporating depressive symptoms into our model as a covariate, the moderate to high depressive symptoms were associated with significantly and clinically important worse PROMIS PF (ß: -4.00, 95% CI: -7.00 to -1.00, P = .01) and PI (ß: 3.16, 95% CI: -0.55 to 5.76, P = .02) scores. Conclusion: Following ankle fracture surgery, all patients tend to clinically improve by 3-6 months postoperatively and then continue to appreciate this clinical improvement. Although patients with moderate to high depressive symptoms also clinically improve following the same trajectory, they tend to do so to a lesser level than those who have low depressive symptoms. Level of Evidence: Level III, case-control study.

Chromatin modules and their implication in genomic organization and gene regulation.

Regulation of gene expression is a complex but highly guided process. While genomic technologies and computational approaches have allowed high-throughput mapping of cis-regulatory elements (CREs) and their interactions in 3D, their precise role in regulating gene expression remains obscure. Recent complementary observations revealed that interactions between CREs frequently result in the formation of small-scale functional modules within topologically associating domains. Such chromatin modules likely emerge from a complex interplay between regulatory machineries assembled at CREs, including site-specific binding of transcription factors. Here, we review the methods that allow identifying chromatin modules, summarize possible mechanisms that steer CRE interactions within these modules, and discuss outstanding challenges to uncover how chromatin modules fit in our current understanding of the functional 3D genome.