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Ex vivo regional gene therapy is a promising tissue-engineering strategy for bone regeneration: osteogenic mesenchymal stem cells (MSCs) can be genetically modified to express an osteoinductive stimulus (e.g., bone morphogenetic protein-2), seeded onto an osteoconductive scaffold, and then implanted into a bone defect to exert a therapeutic effect. Compared to recombinant human BMP-2 (rhBMP-2), which is approved for clinical use, regional gene therapy may have unique benefits related to the addition of MSCs and the sustained release of BMP-2. However, the cellular and transcriptional mechanisms regulating the response to these two strategies for BMP-2 mediated bone regeneration are largely unknown. Here, for the first time, we performed single-cell RNA sequencing (10x Genomics) of hematoma tissue in six rats with critical-sized femoral defects that were treated with either regional gene therapy or rhBMP-2. Our unbiased bioinformatic analysis of 2393 filtered cells in each group revealed treatment-specific differences in their cellular composition, transcriptional profiles, and cellular communication patterns. Gene therapy treatment induced a more robust chondrogenic response, as well as a decrease in the proportion of fibroblasts and the expression of profibrotic pathways. Additionally, gene therapy was associated with an anti-inflammatory microenvironment; macrophages expressing canonical anti-inflammatory markers were more common in the gene therapy group. In contrast, pro-inflammatory markers were more highly expressed in the rhBMP-2 group. Collectively, the results of our study may offer insights into the unique pathways through which ex vivo regional gene therapy can augment bone regeneration compared to rhBMP-2. Furthermore, an improved understanding of the cellular pathways involved in segmental bone defect healing may allow for the further optimization of regional gene therapy or other bone repair strategies. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to describe utilization, demographics, complications, and revisions for patients with degenerative spondylolisthesis (DS) with stenosis undergoing decompression or decompression with fusion in the United States. Methods: A national insurance database was used to identify patients who underwent either decompression and fusion or decompression alone for management of DS from 2010–2022. Utilization trends, demographics, and complications for each procedure were compared. Results: A total of 162,878 patients were identified, of which 78,043 patients underwent combined single-level lumbar decompression and fusion and 84,835 underwent single-level lumbar decompression alone. Between 2010–2021, lumbar decompression and fusion became the predominant surgical intervention for DS in 2016 and continued to account for more than half of all procedures during the remainder of the study period. Factors such as age, sex, comorbidities, geographic region, and physician specialty training were associated with procedure choice. Decompression with fusion was associated with a lower risk of revision surgery up to 5 years postoperatively and an overall lower incidence of 30-day complications. Conclusion: Decompression with fusion has become the most common treatment for lumbar DS over the past decade despite a lack of compelling evidence supporting its use compared to decompression alone. A variety of patient and surgeon-specific factors is associated with procedure choice. After accounting for cofounders, we identified treatment-specific complications that may be valuable when counseling patients. [ABSTRACT FROM AUTHOR]

Author(s): Simon Pollett, Michael A. Johansson, Nicholas G. Reich, David Brett-Major, Sara Y. Del Valle, Srinivasan Venkatramanan, Rachel Lowe, Travis Porco, Irina Maljkovic Berry, Alina Deshpande, Moritz U. G. Kraemer, [...]

Objective: The objective of this study was to examine clinical and epidemiological information collected by Student Health Center (SHC) providers on HIV-positive students, and benchmark this information against Infectious Disease Society of America guidelines. Participants: Students who utilized the SHC and had an ICD-9 code indicating positive HIV status between 2005 and 2015 (3 = 7). Methods: In June 2016, we accessed the free-form provider notes of the SHC's electronic medical records to identify specific, recorded epidemiological and clinical information. Results: Seven unique students sought care at the SHC during the study period. Current sexual risk taking and other known behavioral risk factors were absent from all records, along with CD4 count and viral load. ART status was only available for one patient, and he was not on ART. The information collected failed to meet IDSA benchmarks. Conclusion: Clinically- and epidemiologically-relevant information is not systematically collected from HIV-positive students at SHCs.

Objective: Cocaine use is increasing. Comorbidities and diagnostic sequencing are needed among college students to inform treatment of cocaine use disorder (CUD). Method: Using electronic medical records from the psychiatric clinic at the student health care center of a large, public university from 2005 to 2015, patients diagnosed with CUD were identified. Their top mental health conditions were identified and assessed to see whether the first diagnosis of these conditions was made (1) before, (2) at the same time as, or (3) after the first diagnosis of CUD. Results: Among the 50 CUD patients, their most common mental health comorbidities were alcohol use disorder, anxiety, depression, and cannabis use disorder. Anxiety and depression were likely to be diagnosed before CUD; alcohol and cannabis use disorders were likely to be diagnosed concurrently with CUD. Conclusion: Diagnostic sequencing can be used to inform screening, workup, and treatment for patients with CUD.

Background: The Internet is an important source of information for patients, but its effectiveness relies on the readability of its content. Patient education materials (PEMs) should be written at or below a sixth-grade reading level as outlined by agencies such as the American Medical Association. This study assessed PEMs' readability for the novel anterior vertebral body tethering (AVBT), distraction-based methods, and posterior spinal fusion (PSF) in treating pediatric spinal deformity. Methods: An online search identified PEMs using the terms "anterior vertebral body tethering," "growing rods scoliosis," and "posterior spinal fusion pediatric scoliosis." We selected the first 20 general medical websites (GMWs) and 10 academic health institution websites (AHIWs) discussing each treatment (90 websites total). Readability tests for each webpage were conducted using Readability Studio software. Reading grade levels (RGLs), which correspond to the US grade at which one is expected to comprehend the text, were calculated for sources and independent t tests compared with RGLs between treatment types. Results: The mean RGL was 12.1 ± 2.0. No articles were below a sixth-grade reading level, with only 2.2% at the sixth-grade reading level. AVBT articles had a higher RGL than distraction-based methods (12.7 ± 1.6 vs 11.9 ± 1.9, P = 0.082) and PSF (12.7 ± 1.6 vs 11.6 ± 2.3, P = 0.032). Materials for distraction-based methods and PSF were comparable (11.9 ± 1.9 vs 11.6 ± 2.3, P = 0.566). Among GMWs, AVBT materials had a higher RGL than distraction-based methods (12.9 ± 1.4 vs 12.1 ± 1.8, P = 0.133) and PSF (12.9 ± 1.4 vs 11.4 ± 2.4, P = 0.016). Clinical Relevance: Patients' health literacy is important for shared decision-making. Assessing the readability of scoliosis treatment PEMs guides physicians when sharing resources and discussing treatment with patients. Conclusion: Both GMWs and AHIWs exceed recommended RGLs, which may limit patient and parent understanding. Within GMWs, AVBT materials are written at a higher RGL than other treatments, which may hinder informed decision-making and patient outcomes. Efforts should be made to create online resources at the appropriate RGL. At the very least, patients and parents may be directed toward AHIWs; RGLs are more consistent. [ABSTRACT FROM AUTHOR]

Author(s): Simon Pollett 1, Michael A. Johansson 2, Nicholas G. Reich 3, David Brett-Major 4, Sara Y. Del Valle 5, Srinivasan Venkatramanan 6, Rachel Lowe 7,8, Travis Porco 9, Irina [...], Background The importance of infectious disease epidemic forecasting and prediction research is underscored by decades of communicable disease outbreaks, including COVID-19. Unlike other fields of medical research, such as clinical trials and systematic reviews, no reporting guidelines exist for reporting epidemic forecasting and prediction research despite their utility. We therefore developed the EPIFORGE checklist, a guideline for standardized reporting of epidemic forecasting research. Methods and findings We developed this checklist using a best-practice process for development of reporting guidelines, involving a Delphi process and broad consultation with an international panel of infectious disease modelers and model end users. The objectives of these guidelines are to improve the consistency, reproducibility, comparability, and quality of epidemic forecasting reporting. The guidelines are not designed to advise scientists on how to perform epidemic forecasting and prediction research, but rather to serve as a standard for reporting critical methodological details of such studies. Conclusions These guidelines have been submitted to the EQUATOR network, in addition to hosting by other dedicated webpages to facilitate feedback and journal endorsement.

The management of critical-sized bone defects caused by nonunion, trauma, infection, malignancy, pseudoarthrosis, and osteolysis poses complex reconstruction challenges for orthopedic surgeons. Current treatment modalities, including autograft, allograft, and distraction osteogenesis, are insufficient for the diverse range of pathology encountered in clinical practice, with significant complications associated with each. Therefore, there is significant interest in the development of delivery vehicles for growth factors to aid in bone repair in these settings. This article reviews innovative strategies for the management of critical-sized bone loss, including novel scaffolds designed for controlled release of rhBMP, bioengineered extracellular vesicles for delivery of intracellular signaling molecules, and advances in regional gene therapy for sustained signaling strategies. Improvement in the delivery of growth factors to areas of significant bone loss has the potential to revolutionize current treatment for this complex clinical challenge. [ABSTRACT FROM AUTHOR]

Background: This study directly compares the recurrence rates of dorsal wrist ganglion cysts in patients treated via open surgical excision versus arthroscopic surgical excision. We hypothesized that there would be no difference between recurrence rates with these 2 surgical options. Methods: We retrospectively reviewed the charts of all patients with a dorsal ganglion cyst undergoing either open or arthroscopic surgical excision at a single academic center with 3 fellowship-trained attending hand surgeons from 2012 to 2017. Charts were identified using Current Procedural Terminology codes and were reviewed using postoperative office notes for preoperative and postoperative symptoms, episodes of recurrence, time at which recurrence occurred, subsequent operations, and outcome at final follow-up. Results: The charts of 172 patients undergoing either arthroscopic or open dorsal ganglion excision were reviewed. Nine of 54 (16.7%) arthroscopic excisions resulted in cyst recurrence, while 8 of 118 (6.8%) open excisions resulted in cyst recurrence (P =.044). Two of 9 (22%) recurrences after arthroscopic ganglion excision versus 2 of 8 (25%) recurrences after open ganglion excision underwent repeat surgical intervention. Time to recurrence, as well as final follow-up, was not statistically different between groups. Conclusions: Dorsal wrist ganglion cysts are the most common benign soft tissue mass of the upper extremity, but it remains unknown whether arthroscopic or open surgical excision leads to lower recurrence rate. Scant literature exists directly comparing these 2 methods of surgical excision. This study suggests that open excision of dorsal wrist ganglia leads to a lower recurrence rate than does arthroscopic excision. [ABSTRACT FROM AUTHOR]

There is a limited amount of literature examining torso biomechanics and stride length while addressing their relationship to medial elbow injuries in the adolescent baseball pitcher. Anatomical changes, growth, early sport specialization, multiple team participation, mound distance, mound height, and high pitch counts place adolescent pitchers at an exceptionally higher risk for medial elbow injuries. Existing evidence indicates that decreased stride length and altered trunk rotation is correlated with increased medial elbow loading for the adolescent overhead athlete. Further research is required to quantify adequate parameters for torso kinematics, control, and their correlation to stride length, in order to positively affect the biomechanical transfer of energy and potentially prevent injuries during the overhead throwing motion. The purpose of this clinical commentary is to examine and summarize the role of torso biomechanics and stride length in relation to medial elbow injuries in adolescent baseball pitchers. Level of Evidence 5 [ABSTRACT FROM AUTHOR]