Complications and Functional Outcomes after Reconstruction of the Proximal Humerus with Allograft-Prosthetic Composite - A Systematic Review of the Literature.

INTRODUCTION: Allograft prosthetic composite (APC) reconstruction is performed after resection of proximal humerus tumors or failure of arthroplasty implants. There is limited literature on the postoperative outcomes of this technique. We sought to assess implant survival, failure rates, and postoperative functional outcomes after APC reconstruction of the proximal humerus. METHODS: A systematic review of the PubMed and Embase databases was conducted. The study was registered on PROSPERO (ID: 448663). The STROBE checklist was used for quality assessment. Implant failure was determined using the Henderson classification for biological reconstruction. Functional outcome was primarily assessed using the Musculoskeletal Tumor Society (MSTS) score at last follow-up. RESULTS: Twenty-five studies with a total of 488 patients were included. Mean follow-up in reporting studies ranged from 2.5 to 10 years. Five-year revision-free survival for implants ranged from 41 to 92%. Overall implant failure rate ranged from 9 to 54%, and reoperation rate ranged from 0 to 55%. Graft-host non-union (type 2) was the most common mode of failure, with rates ranging from 0 to 75%. The mean MSTS scores at last follow-up ranged from 57 to 90% across studies. A trend towards better functional outcomes was seen in patients having an APC with a reverse total shoulder arthroplasty (rTSA) compared with those with hemiarthroplasty (HA). CONCLUSIONS: APCs show promise in proximal shoulder reconstruction, with heterogenous functional outcomes that are non-inferior to other reconstruction techniques. Graft host non-union is a common mode of failure and remains a concern in this type of prosthesis. Future studies should compare rTSA-APCs and rTSA endoprostheses while controlling for potential confounders.

Comparing the Efficacy of Targeted and Blast Portal Messaging in Message Opening Rate and Anticoagulation Initiation in Patients With Atrial Fibrillation in the Preventing Preventable Strokes Study II: Prospective Cohort Study.

BACKGROUND: The gap in anticoagulation use among patients with atrial fibrillation (AF) is a major public health threat. Inadequate patient education contributes to this gap. Patient portal-based messaging linked to educational materials may help bridge this gap, but the most effective messaging approach is unknown. OBJECTIVE: This study aims to compare the responsiveness of patients with AF to an AF or anticoagulation educational message between 2 portal messaging approaches: sending messages targeted at patients with upcoming outpatient appointments 1 week before their scheduled appointment (targeted) versus sending messages to all eligible patients in 1 blast, regardless of appointment scheduling status (blast), at 2 different health systems: the University of Massachusetts Chan Medical School (UMass) and the University of Florida College of Medicine-Jacksonville (UFL). METHODS: Using the 2 approaches, we sent patient portal messages to patients with AF and grouped patients by high-risk patients on anticoagulation (group 1), high-risk patients off anticoagulation (group 2), and low-risk patients who may become eligible for anticoagulation in the future (group 3). Risk was classified based on the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age between 65 and 74 years, and sex category (CHA2DS2-VASc) score. The messages contained a link to the Upbeat website of the Heart Rhythm Society, which displays print and video materials about AF and anticoagulation. We then tracked message opening, review of the website, anticoagulation use, and administered patient surveys across messaging approaches and sites using Epic Systems (Epic Systems Corporation) electronic health record data and Google website traffic analytics. We then conducted chi-square tests to compare potential differences in the proportion of patients opening messages and other evaluation metrics, adjusting for potential confounders. All statistical analyses were performed in SAS (version 9.4; SAS Institute). RESULTS: We sent 1686 targeted messages and 1450 blast messages. Message opening was significantly higher with the targeted approach for patients on anticoagulation (723/1156, 62.5% vs 382/668, 57.2%; P=.005) and trended the same in patients off anticoagulation; subsequent website reviews did not differ by messaging approach. More patients off anticoagulation at baseline started anticoagulation with the targeted approach than the blast approach (adjusted percentage 9.3% vs 2.1%; P<.001). CONCLUSIONS: Patients were more responsive in terms of message opening and subsequent anticoagulation initiation with the targeted approach.

Extracellular Vesicles: An Emerging Clinical Opportunity in Musculoskeletal Disease.

Extracellular vesicles (EVs) are important mediators of cell-to-cell communication in the extracellular space. These membranous nanoparticles carry various molecules, often referred to as "cargo," which are delivered to nearby target cells. In the past decade, developments in nanotechnology have allowed for various new laboratory techniques for the increased utilization of EVs in cellular and animal studies. Such techniques have evolved for the isolation, characterization, and delivery of EVs to biological tissues. This emerging technology has immense clinical potential for both diagnostic and therapeutic applications. Various EV cargo molecules, including DNA, RNA, and proteins, can act as pathological biomarkers. Furthermore, EVs derived from certain cell sources have shown therapeutic benefit in certain pathologies. In addition to their native therapeutic benefit, EVs can be engineered to carry and selectively deliver therapeutic agents. While EVs have gained increasing interest in various pathologies, few studies have compiled their clinical potential in musculoskeletal pathologies. To bridge this gap, we present an overview of EVs, introduce current laboratory preparation techniques, and outline the most recent literature regarding the potential therapeutic applications of EVs in musculoskeletal pathologies.

Impact of a pharmacist intervention on DOAC knowledge and satisfaction in ambulatory patients.

Patient education of high-risk medications such as direct oral anticoagulants (DOACs) is limited in ambulatory care settings. Clinical pharmacists are uniquely equipped to educate patients about DOACS but seldom interact with patients in those settings where patient education and satisfaction are often overlooked. Recently, the Anticoagulation Forum endorsed a checklist (DOAC Checklist) to guide and educate patients initiating or resuming DOACs. We assessed the impact on knowledge and satisfaction of an intervention framed around the checklist. Randomized clinical trial. Ambulatory patients starting a DOAC or resuming one after setback (bleeding, stroke, or transient ischemic attack) in an ambulatory setting (office, emergency department, or short stay hospitalization). Three educational clinical pharmacist tele-visits, hotline access to the pharmacist, and coordination with continuity providers in 3 months. Patient knowledge scores from a 15-item DOAC-related questionnaire and satisfaction scores from an abbreviated version of the Duke Anticoagulation Satisfaction Survey (DASS). Of 561 randomized patients, 436 completed our follow-up surveys. Knowledge scores were similar for the 233 intervention patients vs. 203 control patients (63.7% vs 62.2% correct). Satisfaction scores on the 7-point Likert scale were virtually identical (6.24 and 6.22). Our pharmacist-led intervention framed around the DOAC checklist had little impact on knowledge and satisfaction. Delays between intervention end and completion of the follow-up questionnaires may have obscured benefits experienced earlier. More intensive education or strategies other than telephone-based consultation may be required to produce sustained knowledge.TRN: NCT04068727 retrospectively registered on August 22, 2019.

Preoperative walking intervention did not appear to improve patient-reported postoperative recovery in older adults with frailty traits: Randomized trial.

OBJECTIVES: To assess the impact of a preoperative walking intervention on improving postoperative recovery in at-risk frail older adult patients. STUDY TYPE: Unblinded, randomized controlled trial which assigned patients to intervention versus control. POPULATION: Patients aged 60+ scheduled for surgery 3-8 weeks from randomization scoring 4+ on the Edmonton Frail Scale. INTERVENTION: Preoperative walking enhanced by goal setting with an activity monitor and telephonic coaching. MAIN OUTCOMES: Quality of Recovery 9-item instrument total score and a modified version of the Abdominal Surgery Impact Scale total score. RESULTS: A total of 83 patients were analyzed. Postoperative recovery scores were similar in intervention vs control - Quality of Recovery-9 item instrument total score 14.1 vs. 14.1 (P = .94) and modified Abdominal and Surgery Impact Scale total score 82.8 vs. 79.2 (P = .93). Few intervention patients met their daily step count goals. Despite this, intervention patients improved average daily step counts significantly. CONCLUSIONS: Preoperative walking bolstered with activity monitor and remote coaching did not appear to lead to improved postoperative recovery in older adults with frailty traits. Further research is necessary to see if a similar intervention in specific surgery types or a more intense version of the intervention can improve recovery.

Preventing preventable strokes: A study protocol to push guideline-driven atrial fibrillation patient education via patient portal.

Background: The main approach to preventing stroke in patients with atrial fibrillation (AF) is anticoagulation (AC), but only about 60% of at-risk individuals are on AC. Patient-facing electronic health record-based interventions have produced mixed results. Little is known about the impact of health portal-based messaging on AC use. Objective: The purpose of this study was describe a protocol we will use to measure the association between AC use and patient portal message opening. We also will measure patient attitudes toward education materials housed on a professional society Web site. Methods: We will send portal messages to patients aged ≥18 years with AF 1 week before an office/teleconference visit with a primary care or cardiology provider. The message will be customized for 3 groups of patients: those on AC; those at elevated risk but off AC; and those not currently at risk but may be at risk in the future. Within the message, we will embed a link to UpBeat.org, a Web site of the Heart Rhythm Society containing patient educational materials. We also will embed a link to a survey. Among other things, the survey will request patients to rate their attitude toward the Heart Rhythm Society Web pages. To measure the effectiveness of the intervention, we will track AC use and its association with message opening, adjusting for potential confounders. Conclusion: If we detect an increase in AC use correlates with message opening, we will be well positioned to conduct a future comparative effectiveness trial. If patients rate the UpBeat.org materials highly, patients from other institutions also may benefit from receiving these materials.

Asynchronous excitatory neuron development in an isogenic cortical spheroid model of Down syndrome.

The intellectual disability (ID) in Down syndrome (DS) is thought to result from a variety of developmental deficits such as alterations in neural progenitor division, neurogenesis, gliogenesis, cortical architecture, and reduced cortical volume. However, the molecular processes underlying these neurodevelopmental changes are still elusive, preventing an understanding of the mechanistic basis of ID in DS. In this study, we used a pair of isogenic (trisomic and euploid) induced pluripotent stem cell (iPSC) lines to generate cortical spheroids (CS) that model the impact of trisomy 21 on brain development. Cortical spheroids contain neurons, astrocytes, and oligodendrocytes and they are widely used to approximate early neurodevelopment. Using single cell RNA sequencing (scRNA-seq), we uncovered cell type-specific transcriptomic changes in the trisomic CS. In particular, we found that excitatory neuron populations were most affected and that a specific population of cells with a transcriptomic profile resembling layer IV cortical neurons displayed the most profound divergence in developmental trajectory between trisomic and euploid genotypes. We also identified candidate genes potentially driving the developmental asynchrony between trisomic and euploid excitatory neurons. Direct comparison between the current isogenic CS scRNA-seq data and previously published datasets revealed several recurring differentially expressed genes between DS and control samples. Altogether, our study highlights the power and importance of cell type-specific analyses within a defined genetic background, coupled with broader examination of mixed samples, to comprehensively evaluate cellular phenotypes in the context of DS.

Supervised preoperative walking on increasing early postoperative stamina and mobility in older adults with frailty traits: A pilot and feasibility study.

Background and Aims: Frail older adults are more than twice as likely to experience postoperative complications. Preoperative exercise may better prepare these patients through improved stamina and mobility experienced in the days following surgery. We measured the impact of a walking intervention using an activity tracker and coaching on postoperative stamina, and mobility in older adults with frailty traits. Methods: We included patients aged 60+ and scoring 4+ on the Edmonton Frailty Scale. We then randomized patients to intervention versus control stratified by anticipated hospital stay (1 night vs. 2+ night) and baseline stamina (i.e., 6-min walk distance [6MWD]). Intervention patients received an activity tracker and linked smart phone. An athletic trainer (AT) prescribed a daily step count goal and titrated this up after checking in with patients during weekly telephone calls. Controls received general walking recommendations. We then measured postoperative 6MWD 1-3 days after surgery. We also assessed postoperative mobility by measuring steps walked the day after surgery using a thigh-worn monitor. Because many patients could not walk postoperatively, we compared intervention-control difference in both 6MWD and steps using Wilcoxon rank testing and Tobit and ordinal logistic regression adjusting for several patient characteristics. Results: We randomized 104 eligible patients; 80 patients remained for final analysis. There was no difference in intervention versus control postoperative 6MWD (median 72 vs. 74 m Wilcoxon p = 0.54) or postoperative steps taken (median 128 vs. 51 steps Wilcoxon p = 0.76). Analysis adjusting for patient characteristics was consistent with these findings. Conclusion: Our intervention consisting of goal setting with an activity tracker and telephonic coaching by an AT did not appear to improve stamina or mobility measured in the days after surgery. Small sample size limited our ability to examine this impact in subsets defined by surgical specialty or baseline stamina.

The Role of Extracellular Vesicles in Diseases of the Ear, Nose, and Throat.

Extracellular vesicles (EVs) are membranous nanoparticles produced by most cell types into the extracellular space and play an important role in cell-to-cell communication. Historically, EVs were categorized based on their methods of biogenesis and size into three groups: exosomes, microvesicles, and apoptotic bodies. Most recently, EV nomenclature has evolved to categorize these nanoparticles based on their size, surface markers, and/or the cell type which secreted them. Many techniques have been adopted in recent years which leverage these characteristics to isolate them from cell culture media and biological fluids. EVs carry various "cargo", including DNA, RNA, proteins, and small signaling molecules. After isolation, EVs can be characterized by various methods to analyze their unique cargo profiles which define their role in cell-to-cell communication, normal physiology, and disease progression. The study of EV cargo has become more common recently as we continue to delineate their role in various human diseases. Further understanding these mechanisms may allow for the future use of EVs as novel biomarkers and therapeutic targets in diseases. Furthermore, their unique cargo delivery mechanisms may one day be exploited to selectively deliver therapeutic agents and drugs. Despite the growing research interest in EVs, limited studies have focused on the role of EVs in the diseases of the ear, nose, and throat. In this review, we will introduce EVs and their cargo, discuss methods of isolation and characterization, and summarize the most up-to-date literature thus far into the role of EVs in diseases of the ear, nose, and throat.

Sonic Hedgehog Pathway Modulation Normalizes Expression of Olig2 in Rostrally Patterned NPCs With Trisomy 21.

The intellectual disability found in people with Down syndrome is associated with numerous changes in early brain development, including the proliferation and differentiation of neural progenitor cells (NPCs) and the formation and maintenance of myelin in the brain. To study how early neural precursors are affected by trisomy 21, we differentiated two isogenic lines of induced pluripotent stem cells derived from people with Down syndrome into brain-like and spinal cord-like NPCs and promoted a transition towards oligodendroglial fate by activating the Sonic hedgehog (SHH) pathway. In the spinal cord-like trisomic cells, we found no difference in expression of OLIG2 or NKX2.2, two transcription factors essential for commitment to the oligodendrocyte lineage. However, in the brain-like trisomic NPCs, OLIG2 is significantly upregulated and is associated with reduced expression of NKX2.2. We found that this gene dysregulation and block in NPC transition can be normalized by increasing the concentration of a SHH pathway agonist (SAG) during differentiation. These results underscore the importance of regional and cell type differences in gene expression in Down syndrome and demonstrate that modulation of SHH signaling in trisomic cells can rescue an early perturbed step in neural lineage specification.