Arthroscopic Remplissage Combined With Bankart Repair Results in a Higher Rate of Return to Sport in Athletes Compared With Bankart Repair Alone or the Latarjet Procedure: A Systematic Review and Meta-analysis.

BACKGROUND: Traumatic anterior shoulder instability affects athletes at a higher rate compared with the general population. In recent years, indications for arthroscopic remplissage, an adjunct procedure classically used to reduce the recurrence of anterior shoulder instability in patients with off-track Hill-Sachs lesions, have expanded. PURPOSE: To investigate return-to-sport (RTS) rates, functional outcomes, and adverse events in athletes who underwent arthroscopic Bankart repair with remplissage compared with surgical alternatives such as Bankart repair alone or the Latarjet procedure. STUDY DESIGN: Systematic review and meta-analysis; Level of evidence, 4. METHODS: A literature review of the Embase, PubMed (MEDLINE), and Web of Science databases was conducted for articles published before May 22, 2022. For the systematic review, 16 of 457 studies that reported RTS rates at any time point after remplissage were deemed eligible for inclusion in quantitative analysis and 17 of 457 studies in qualitative analysis. For the meta-analysis, 8 of 457 studies reported RTS rates after remplissage compared with surgical alternatives including Bankart repair alone or the Latarjet procedure and were deemed eligible for inclusion. RESULTS: In total, 538 athletes underwent remplissage and were included in the study. RTS at any level was achieved by 86% (395/457) of patients, and the odds of RTS at any level were significantly higher after remplissage compared with surgical alternatives (odds ratio [OR], 2.71 [95% CI, 1.14-6.43]; P = .02). The odds of RTS at a previous or higher level were also significantly higher after remplissage compared with surgical alternatives (OR, 2.07 [95% CI, 1.29-3.31]; P = .002). The mean Rowe score increased significantly from 43.9 ± 7.77 preoperatively (n = 173) to 92.2 ± 4.02 after remplissage (n = 397) (P < .001), but there was no significant difference in Rowe scores between remplissage and surgical alternatives (P = .54). After remplissage, the recurrence rate was 5.0% for athletes (n = 220) and 7.3% for all patients (n = 634), with a mean time to recurrence of 24.0 ± 12.5 months. Reoperations occurred in 3.6% of athletes (n = 110) and 4.1% of all patients (n = 445). Recurrence and reoperations were significantly less likely after remplissage compared with surgical alternatives (OR, 0.18 [95% CI, 0.08-0.39]; P < .001 and OR, 0.17 [95% CI, 0.06-0.50]; P = .001, respectively). CONCLUSION: Arthroscopic Bankart repair with remplissage augmentation significantly improved RTS rates among athletes, both at any level and at previous levels of play. Additionally, remplissage appeared to significantly decrease recurrence and reoperation rates compared with surgical alternatives such as Bankart repair alone or the Latarjet procedure.

Engineering Human Circulating Monocytes/Macrophages by Systemic Deliverable Gene Editing.

Delivery of plasmid DNA to transfect human primary macrophages is extremely difficult, especially for genetic engineering. Engineering macrophages is imperative for the treatment of many diseases including infectious diseases, cancer, neurological diseases, and aging. Unfortunately, plasmid does not cross the nuclear membranes of terminally differentiated macrophages to integrate the plasmid DNA (pDNA) into their genome. To address this issue, we have developed a core-shell nanoparticle (NP) using our newly created cationic lipid to deliver the anti-inflammatory cytokine IL-4 pDNA (IL-4pDNA-NPs). Human blood monocyte-derived macrophages (MDM) were effectively transfected with IL-4pDNA-NPs. IL-4pDNA-NPs were internalized in MDM within 30 minutes and delivered into the nucleus within 2 hours. Exogenous IL-4 expression was detected within 1 - 2 days and continued up to 30 days. Functional IL-4 expression led to M2 macrophage polarization in vitro and in an in vivo mouse model of inflammation. These data suggest that these NPs can protect pDNA from degradation by nucleases once inside the cell, and can transport pDNA into the nucleus to enhance gene delivery in macrophages in vitro and in vivo. In this research, we developed a new method to deliver plasmids into the nucleus of monocytes and macrophages for gene-editing. Introducing IL-4 pDNA into macrophages provides a new gene therapy solution for the treatment of various diseases.

Dual-sgRNA CRISPR/Cas9 knockout of PD-L1 in human U87 glioblastoma tumor cells inhibits proliferation, invasion, and tumor-associated macrophage polarization.

Programmed death ligand 1 (PD-L1) plays a key role in glioblastoma multiforme (GBM) immunosuppression, vitality, proliferation, and migration, and is therefore a promising target for treating GBM. CRISPR/Cas9-mediated genomic editing can delete both cell surface and intracellular PD-L1. This systemic deliverable genomic PD-L1 deletion system can be used as an effective anti-GBM therapy by inhibiting tumor growth and migration, and overcoming immunosuppression. To target PD-L1 for CRISPR/Cas9 gene editing, we first identified two single guide RNA (sgRNA) sequences located on PD-L1 exon 3. The first sgRNA recognizes the forward strand of human PD-L1 near the beginning of exon 3 that allows editing by Cas9 at approximately base pair 82 (g82). The second sgRNA recognizes the forward strand of exon 3 that directs cutting at base pair 165 (g165). A homology-directed repair template (HDR) combined with the dual-sgRNAs was used to improve PD-L1 knockout specificity and efficiency. sgRNAs g82 and g165 were cloned into the multiplex CRISPR/Cas9 assembly system and co-transfected with the HDR template in human U87 GBM cells (g82/165 + HDR). T7E1 analysis suggests that the dual-sgRNA CRISPR/Cas9 strategy with a repair template was capable of editing the genomic level of PD-L1. This was further confirmed by examining PD-L1 protein levels by western blot and immunofluorescence assays. Western blot analysis showed that the dual-sgRNAs with the repair template caused a 64% reduction of PD-L1 protein levels in U87 cells, while immunostaining showed a significant reduction of intracellular PD-L1. PD-L1 deletion inhibited proliferation, growth, invasion and migration of U87 cells, indicating intracellular PD-L1 is necessary for tumor progression. Importantly, U87 cells treated with g82/165 + HDR polarized tumor-associated macrophages (TAM) toward an M1 phenotype, as indicated by an increase in TNF-α and a decrease in IL-4 secretions. This was further confirmed with flow cytometry that showed an increase in the M1 markers Ly6C + and CD80 +, and a decrease in the M2 marker CD206 + both in vitro and in vivo. Utilizing dual-sgRNAs and an HDR template with the CRISPR/Cas9 gene-editing system is a promising avenue for the treatment of GBM.

Intensity of usual care physical therapy during inpatient rehabilitation for people with neurologic diagnoses.

BACKGROUND: Early, intense rehabilitation is essential to promote recovery after stroke, spinal cord injury (SCI), and traumatic brain injury (TBI). However, intensity of usual care rehabilitation interventions during inpatient rehabilitation are poorly characterized. OBJECTIVE: To describe the intensity of usual care rehabilitation interventions completed during the subacute phase of recovery from neurologic injury. DESIGN: Observational. SETTING: Inpatient rehabilitation facility. INTERVENTIONS: Twenty-two usual care physical therapy interventions were grouped into six categories: gait (four activities), functional (two), strengthening (four), aerobic (six), balance (four), and wheelchair (two). PATIENTS: Patients admitted to inpatient rehabilitation with a primary diagnosis of stroke, SCI or TBI within 6 months of injury. MAIN OUTCOME MEASURE(S): Cardiovascular intensity (physiological and perceived) was recorded during rehabilitation activity sessions. Physiological intensity was assessed by heart rate reserve (HRR) via a Polar A370 Fitness Watch and characterized as very light (<30%), light (30-39%), moderate (40-59%), vigorous (60-89%), and near maximal (≥90%). Perceived intensity was assessed using the Rating of Perceived Exertion scale. RESULTS: Patients (stroke n = 16 [number of activity sessions = 338/average session duration = 16.4 min]; SCI n = 15 [299/27.4 min]; TBI n = 15 [340/14.2 min]) participated. For patients with stroke, moderate-to-vigorous HRR was attained between 42% (aerobic exercise) to 55% (wheelchair propulsion) of activity sessions. For patients with SCI, moderate-to-vigorous HRR was attained between 29% (strength training) to 46% (gait training) of activity sessions. For patients with TBI, moderate-to-vigorous HRR was attained between 29% (balance activities) to 47% (gait training) of activity sessions. Associations between HRR and rate of perceived exertion were very weak across stroke (r = 0.12), SCI (r = 0.18), and TBI (r = 0.27). CONCLUSIONS: Patients with stroke, SCI, and TBI undergoing inpatient rehabilitation achieve moderate-to-vigorous intensity during some usual care activities such as gait training. Patient perception of intensity was dissimilar to physiological response.