A Case Report of Bilateral Lipoma Arborescens: An Unusual Consideration for Knee Pain.

Introduction: Lipoma arborescens (LAs) is a benign, intra-articular proliferation of fat cells in villous projections, creating a tree-like pattern on magnetic resonance imaging (MRI). The suprapatellar pouch is usually affected, and symptoms are typically gradual in nature, and patients may report painless swelling of the knee. Only ten cases of bilateral LA have been reported in the literature so far. Early recognition of this disease process and treatment may help to prevent prolonged symptoms and delays in care. Case Report: A 49-year-old female with bilateral knee pain and intermittent swelling for over 20 years presented to our clinic with complaints of bilateral knee pain and swelling. She had previous steroid injection but no relief. After MRI was obtained concerning for LA, a surgical discussion was had with the patient about arthroscopic removal. She elected to proceed with surgery and underwent arthroscopic debridement of both knees. At her follow-up at 6 months for the right knee and 2 months for the left knee, she had a significant improvement in pain and quality of life. Conclusion: LA of the knee is a rare condition, particularly bilateral, and in this patient, the diagnosis was missed for many years, and her definitive treatment was delayed. In her case, arthroscopic debridement of her bilateral LA proved to be a viable treatment option which significantly improved the patient's quality of life and function.

Postoperative Infection and Revision Surgery Rates in Foot and Ankle Surgery Without Routine Prescription of Prophylactic Antibiotics.

INTRODUCTION: Surgical site infections (SSIs) are associated with patient morbidity and increased healthcare costs. Limited literature in foot and ankle surgery provides guidance about routine administration of postoperative antibiotic prophylaxis. The purpose of this study was to examine the incidence and revision surgery rates of SSI in outpatient foot and ankle surgeries in patients not receiving oral postoperative antibiotic prophylaxis. METHODS: A retrospective review of all outpatient surgeries (n = 1517) conducted by a single surgeon in a tertiary referral academic center was conducted through electronic medical records. Incidence of SSI, revision surgery rate, and associated risk factors were determined. The median follow-up was 6 months. RESULTS: Postoperative infection occurred in 2.9% (n = 44) of the surgeries conducted, with 0.9% of patients (n = 14) requiring return to the operating room. Thirty patients (2.0%) were diagnosed with simple superficial infections, which resolved with local wound care and oral antibiotics. Diabetes (adjusted odds ratio, 2.09; 95% confidence interval, 1.00 to 4.38; P = 0.049) and increasing age (adjusted odds ratio, 1.02; 95% confidence interval, 1.00 to 1.04; P = 0.016) were significantly associated with postoperative infection. DISCUSSION: This study demonstrated low postoperative infection and revision surgery rates without the routine prescription of prophylactic postoperative antibiotics. Increasing age and diabetes are signficant risk factors for developing a postoperative infection.

Distal Femoral Replacement and Extensor Mechanism Repair Reinforced With Synthetic Mesh for Distal Femur Fracture With Patellar Ligament Avulsion.

Acute patellar ligament disruption in the setting of a distal femur fracture is an uncommon presentation with a variety of treatment options available to the practitioner. The following case report presents an 85-year-old female with a highly comminuted supracondylar distal femur fracture with intercondylar extension and a soft-tissue avulsion of the patellar ligament insertion discovered intraoperatively. A detailed technique review for acute patellar ligament repair with suture anchors and synthetic mesh reinforcement in the setting of distal femoral replacement is then provided. One-year follow-up revealed an intact extensor mechanism with minimal extensor lag and a painless gait. Surgeons faced with such a unique, complex problem may consider mesh augmentation of an acute patellar ligament repair while performing distal femoral replacement.

Perceptual-Motor Efficiency and Concussion History Are Prospectively Associated With Injury Occurrences Among High School and Collegiate American Football Players.

BACKGROUND: After a sport-related concussion (SRC), the risk for lower extremity injury is approximately 2 times greater, and the risk for another SRC may be as much as 3 to 5 times greater. PURPOSE: To assess the predictive validity of screening methods for identification of individual athletes who possess an elevated risk of SRC. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Metrics derived from a smartphone flanker test software application and self-ratings of both musculoskeletal function and overall wellness were acquired from American high school and college football players before study participation. Occurrences of core or lower extremity injury (CLEI) and SRC were documented for all practice sessions and games for 1 season. Receiver operating characteristic and logistic regression analyses were used to identify variables that provided the greatest predictive accuracy for CLEI or SRC occurrence. RESULTS: Overall, there were 87 high school and 74 American college football players included in this study. At least 1 CLEI was sustained by 45% (39/87) of high school players and 55% (41/74) of college players. Predictors of CLEI included the flanker test conflict effect ≥69 milliseconds (odds ratio [OR], 2.12; 90% CI, 1.24-3.62) and a self-reported lifetime history of SRC (OR, 1.70; 90% CI, 0.90-3.23). Of players with neither risk factor, only 38% (29/77) sustained CLEI compared with 61% (51/84) of players with 1 or both of the risk factors (OR, 2.56; 90% CI, 1.50-4.36). SRC was sustained by 7 high school players and 3 college players. Predictors of SRC included the Overall Wellness Index score ≤78 (OR, 9.83; 90% CI, 3.17-30.50), number of postconcussion symptoms ≥4 (OR, 8.35; 90% CI, 2.71-25.72), the Sport Fitness Index score ≤78 (OR, 5.16; 90% CI, 1.70-15.65), history of SRC (OR, 4.03; 90% CI, 1.35-12.03), and the flanker test inverse efficiency ratio ≥1.7 (OR, 3.19; 90% CI, 1.08-9.47). CONCLUSION: Survey responses and smartphone flanker test metrics predicted greater injury incidence among individual football players classified as high-risk compared with that for players with a low-risk profile.

Radiographic Outcomes, Union Rates, and Complications Associated With Plantar Implant Positioning for Midfoot Arthrodesis.

BACKGROUND: Midfoot arthrodesis has long been successfully included in the treatment paradigm for a variety of pathologic foot conditions. A concern with midfoot arthrodesis is the rate of nonunion, which historically has been reported between 5% and 10%. Plantar plating has also been noted to be more biomechanically stable when compared to traditional dorsal plating in previous studies. Practical advantages of plantar plating include less dorsal skin irritation and the ability to correct flatfoot deformity from the same medial incision. The purpose of this study is to report the arthrodesis rate, the success of deformity correction, and the complications associated with plantar-based implant placement for arthrodesis of the medial column. METHODS: A retrospective review was undertaken of all consecutive patients between 2012 and 2019 that underwent midfoot arthrodesis with plantar-positioned implants. Radiographic outcomes and complications are reported on 62 patients who underwent midfoot arthrodesis as part of a correction for hallux valgus deformity, flatfoot deformity, degenerative arthritis, Lisfranc injury, or Charcot neuroarthropathy correction. RESULTS: Statistically significant improvement was seen in the lateral talus-first metatarsal angle (Meary angle) and medial arch sag angle for patients treated for flatfoot deformity correction. In patients treated for hallux valgus deformity, there was a reduction in the intermetatarsal angle from 15.4 to 6.8 degrees. The overall nonunion rate was 6.45% in all patients. The rate of nonunion was higher at the NC joint compared to the TMT joint and with compression claw plates. One symptomatic nonunion required revision surgery (1.7%). There were no nonunions when excluding neuroarthropathy patients and smokers. The odds ratio (OR) for nonunion in patients with neuroarthropathy was 6.05 (P < .05), and in active smokers the OR was 2.33 (P < .05). CONCLUSION: Plates placed on the plantar bone surface for midfoot arthrodesis achieved and maintained deformity correction with rare instances of symptomatic hardware for a variety of orthopedic conditions. An overall clinical and radiographic union rate of 94% was achieved. The radiographic union rate improved to 100% when excluding both neuroarthropathy patients and smokers. The incidence of nonunion was higher in smokers, neuroarthropathy patients, naviculocuneiform joint fusions, use of compression claw plates, and when attempting to fuse multiple joints. Incisional healing complications were rarely seen other than in active smokers. LEVEL OF EVIDENCE: Level IV, case series.

Immune modulatory nanoparticle therapeutics for intracerebral glioma.

Background: Previously we showed therapeutic efficacy of unprotected miR-124 in preclinical murine models of glioblastoma, including in heterogeneous genetically engineered murine models by exploiting the immune system and thereby negating the need for direct tumor delivery. Although these data were promising, to implement clinical trials, we required a scalable formulation that afforded protection against circulatory RNases. Methods: We devised lipid nanoparticles that encapsulate and protect the miRs from degradation and provide enhanced delivery into the immune cell compartment and tested in vivo antitumor effects. Results: Treatment with nanoparticle-encapsulated miR-124, LUNAR-301, demonstrated a median survival exceeding 70 days, with an associated reversal of tumor-mediated immunosuppression and induction of immune memory. In both canine and murine models, the safety profile of LUNAR-301 was favorable. Conclusions: For the first time, we show that nanoparticles can direct a therapeutic response by targeting intracellular immune pathways. Although shown in the context of gliomas, this therapeutic approach would be applicable to other malignancies.

Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype.

Glioblastomas are highly infiltrated by diverse immune cells, including microglia, macrophages, and myeloid-derived suppressor cells (MDSCs). Understanding the mechanisms by which glioblastoma-associated myeloid cells (GAMs) undergo metamorphosis into tumor-supportive cells, characterizing the heterogeneity of immune cell phenotypes within glioblastoma subtypes, and discovering new targets can help the design of new efficient immunotherapies. In this study, we performed a comprehensive battery of immune phenotyping, whole-genome microarray analysis, and microRNA expression profiling of GAMs with matched blood monocytes, healthy donor monocytes, normal brain microglia, nonpolarized M0 macrophages, and polarized M1, M2a, M2c macrophages. Glioblastoma patients had an elevated number of monocytes relative to healthy donors. Among CD11b+ cells, microglia and MDSCs constituted a higher percentage of GAMs than did macrophages. GAM profiling using flow cytometry studies revealed a continuum between the M1- and M2-like phenotype. Contrary to current dogma, GAMs exhibited distinct immunological functions, with the former aligned close to nonpolarized M0 macrophages.

PD-L1 expression and prognostic impact in glioblastoma.

BACKGROUND: Therapeutic targeting of the immune checkpoints cytotoxic T-lymphocyte-associated molecule-4 (CTLA-4) and PD-1/PD-L1 has demonstrated tumor regression in clinical trials, and phase 2 trials are ongoing in glioblastoma (GBM). Previous reports have suggested that responses are more frequent in patients with tumors that express PD-L1; however, this has been disputed. At issue is the validation of PD-L1 biomarker assays and prognostic impact. METHODS: Using immunohistochemical analysis, we measured the incidence of PD-L1 expression in 94 patients with GBM. We categorized our results according to the total number of PD-L1-expressing cells within the GBMs and then validated this finding in ex vivo GBM flow cytometry with further analysis of the T cell populations. We then evaluated the association between PD-L1 expression and median survival time using the protein expression datasets and mRNA from The Cancer Genome Atlas. RESULTS: The median percentage of PD-L1-expressing cells in GBM by cell surface staining is 2.77% (range: 0%-86.6%; n = 92), which is similar to the percentage found by ex vivo flow cytometry. The majority of GBM patients (61%) had tumors with at least 1% or more PD-L1-positive cells, and 38% had at least 5% or greater PD-L1 expression. PD-L1 is commonly expressed on the GBM-infiltrating T cells. Expression of both PD-L1 and PD-1 are negative prognosticators for GBM outcome. CONCLUSIONS: The incidence of PD-L1 expression in GBM patients is frequent but is confined to a minority subpopulation, similar to other malignancies that have been profiled for PD-L1 expression. Higher expression of PD-L1 is correlated with worse outcome.

MiR-138 exerts anti-glioma efficacy by targeting immune checkpoints.

BACKGROUND: Antibody therapeutic targeting of the immune checkpoints cytotoxic T-lymphocyte-associated molecule 4 (CTLA-4) and programmed cell death 1 (PD-1) has demonstrated marked tumor regression in clinical trials. MicroRNAs (miRNAs) can modulate multiple gene transcripts including possibly more than one immune checkpoint and could be exploited as immune therapeutics. METHODS: Using online miRNA targeting prediction algorithms, we searched for miRNAs that were predicted to target both PD-1 and CTLA-4. MiR-138 emerged as a leading candidate. The effects of miR-138 on CTLA-4 and PD-1 expression and function in T cells were determined and the therapeutic effect of intravenous administration of miR-138 was investigated in both immune-competent and -incompetent murine models of GL261 glioma. RESULTS: Target binding algorithms predicted that miR-138 could bind the 3' untranslated regions of CTLA-4 and PD-1, which was confirmed with luciferase expression assays. Transfection of human CD4+ T cells with miR-138 suppressed expression of CTLA-4, PD-1, and Forkhead box protein 3 (FoxP3) in transfected human CD4+ T cells. In vivo miR-138 treatment of GL261 gliomas in immune-competent mice demonstrated marked tumor regression, a 43% increase in median survival time (P = .011), and an associated decrease in intratumoral FoxP3+ regulatory T cells, CTLA-4, and PD-1 expression. This treatment effect was lost in nude immune-incompetent mice and with depletion of CD4+ or CD8+ T cells, and miR-138 had no suppressive effect on glioma cells when treated directly at physiological in vivo doses. CONCLUSIONS: MiR-138 exerts anti-glioma efficacy by targeting immune checkpoints which may have rapid translational potential as a novel immunotherapeutic agent.

Engineering cocrystal solubility, stability, and pH(max) by micellar solubilization.

Cocrystals offer great promise in enhancing drug aqueous solubilities, but face the challenge of conversion to a less soluble drug when in contact with solvent. This manuscript shows that differential solubilization of cocrystal components by micelles can impart thermodynamic stability to otherwise unstable cocrystals. The theoretical foundation for controlling cocrystal solubility and stability is presented by considering the contributions of micellar solubilization and ionization of cocrystal components. A surfactant critical stabilization concentration (CSC) and a solution pH (pH(max)) where cocrystal and drug are thermodynamically stable are shown to characterize cocrystal stability in micellar solutions. The solubility, CSC, and pH(max) of carbamazepine cocrystals in micellar solutions of sodium lauryl sulfate predicted by the models are in very good agreement with experimental measurements. The findings from this work demonstrate that cocrystal CSC and pH(max) can be tailored from the selection of coformer and solubilizing additives such as surfactants, thus providing an unprecedented level of control over cocrystal stability and solubility via solution phase chemistry.