Failure rates and clinical outcomes after treatment for long-head biceps brachii tendon pathology: a comparison of three treatment types.

HYPOTHESIS/BACKGROUND: Treatment options for the biceps brachii tendon include tenotomy, arthroscopic tenodesis, and open tenodesis. Few studies to date have compared all treatment options in the context of a rotator cuff repair. METHODS: A retrospective review of 100 patients who underwent arthroscopic supraspinatus repair between 2013 and 2018 with a minimum of one-year follow-up was performed. Patients were separated into the following 4 groups: (1) 57 had isolated supraspinatus repair with no biceps tendon surgery (SSP); (2) 16 had supraspinatus repair and biceps tenotomy; (3) 18 had supraspinatus repair and arthroscopic biceps tenodesis; (4) 9 had supraspinatus repair and an open biceps tenodesis (SSP + OT). The primary outcome was operative time. The secondary outcomes were cost analysis, complications, patient-reported outcome measures, range of motion, and strength testing. RESULTS: The operative time for the SSP + OT group was significantly longer than that of the SSP group (P < .05) but was not significantly longer than that of the other groups. The cost for the SSP group was significantly less than the cost for the SSP + OT and supraspinatus repair and arthroscopic biceps tenodesis groups (P < .05 for both), whereas the cost for the supraspinatus repair and biceps tenotomy group was significantly less than the cost for the SSP + OT group (P < .05). There were no significant differences between groups for complications, all patient-reported outcome measues, all range of motion, and all strength parameters. DISCUSSION/CONCLUSION: Operative time is the longest in open biceps tenodesis and is significantly longer than that of isolated supraspinatus repair. No significant differences in operative times or costs were identified in patients undergoing arthroscopic vs. open biceps tenodesis. All patients, irrespective of the type of biceps tendon procedure, had excellent clinical and functional outcomes at least one year after surgery. There was no difference in clinical or functional outcomes, or complications, among the 4 groups.

Predictive factors for failure of conservative management in the treatment of calcific tendinitis of the shoulder.

BACKGROUND: Calcific tendinitis of the shoulder is a painful condition characterized by the presence of calcium deposits within the tendons of the rotator cuff (RTC). When conservative management fails, arthroscopic surgery for removal of the calcium may be considered. Surgical removal is often followed by RTC repair to address the resulting tendon defect. This study was performed to assess predictive factors for failure of conservative management and to characterize the rate of RTC repair in the setting of calcific tendinitis. We hypothesize that larger calcific lesion would have a higher likelihood to fail conservative treatment. METHODS: A retrospective review of patients who were diagnosed with calcific tendinitis at our institution between 2009 and 2019 was performed. Demographics, comorbidities, pain score (visual analog scale), American Shoulder and Elbow Surgeons score, range of motion, and patient-reported quality of life measures were recorded and analyzed. All patients underwent a radiograph and magnetic resonance imaging. Size of the calcific lesion was measured based on its largest diameter on magnetic resonance imaging. Statistical analysis included chi-square test, independent t-test, and analysis of variance. RESULTS: Two hundred thirty-nine patients were identified in the study period; 127 (53.1%) were women. The mean age was 54 years, and body mass index was 29.2 with a mean follow-up of 6 months. One hundred and sixty had an intact RTC (67.2%) and 78 had a partial RTC tear (32.8%). Ninety-three of 239 (38.9%) patients failed conservative treatment after an average of 4.4 months, necessitating surgical management. Among patients who underwent surgery, the majority of patients (77 of 93 [82.8%]) required a concomitant RTC repair. Subanalysis demonstrates that calcific lesions >1 cm was significantly associated with failure of conservative treatment (odds ratio = 2.86, 95% confidence interval 1.25-6.29, P < .05). All patients who underwent surgery demonstrated significant improvements in pain scores (6.3 to 2.3 visual analog scale), American Shoulder and Elbow Surgeons score (47.9 to 90.49), forward flexion (133° to 146.8°), and external rotation (49.2° to 57.6°) (P < .05) postoperatively. CONCLUSION: Patients with calcific lesions >1 cm had a 2.8× increased likelihood to undergo operative treatment in the setting of calcific tendinitis of the shoulder. Most patients who undergo surgical management for removal of the calcific deposit required a concomitant RTC repair and had significant improvements in shoulder pain and function. This information can be helpful to guide orthopedic surgeons on preoperative planning and discussion when treating calcific tendinitis of the shoulder.

Characterization of plasma-derived protoporphyrin-IX-positive extracellular vesicles following 5-ALA use in patients with malignant glioma.

BACKGROUND: Malignant gliomas are rapidly progressive brain tumors with high mortality. Fluorescence guided surgery (FGS) with 5-aminolevulinic acid (5-ALA) provides fluorescent delineation of malignant tissue, which helps achieve maximum safe resection. 5-ALA-based fluorescence is due to preferential accumulation of the fluorophore protoporphyrin-IX (PpIX) in malignant glioma tissue. Additionally, gliomas cells release extracellular vesicles (EVs) which carry biomarkers of disease. Herein, we performed animal and human studies to investigate whether 5-ALA dosed glioma cells, in vitro and in vivo, release PpIX positive EVs in circulation which can be captured and analyzed. METHODS: We used imaging flow cytometry (IFC) to characterize PpIX-positive EVs released from 5-ALA-dosed glioma cells, glioma-bearing xenograft models, as well as patients with malignant glioma undergoing FGS. FINDINGS: We first show that glioma cells dosed with 5-ALA release 247-fold higher PpIX positive EVs compared to mock dosed glioma cells. Second, we demonstrate that the plasma of glioma-bearing mice (n = 2) dosed with 5-ALA contain significantly higher levels of circulating PpIX-positive EVs than their pre-dosing background (p = 0.004). Lastly, we also show that the plasma of patients with avidly fluorescent tumors (n = 4) undergoing FGS contain circulating PpIX-positive EVs at levels significantly higher than their pre-dosing background (p = 0.00009) and this rise in signal correlates with enhancing tumor volumes (r 2  = 0.888). INTERPRETATION: Our findings highlight the potential of plasma-derived PpIX-positive EV-based diagnostics for malignant gliomas, offering a novel liquid biopsy platform for confirming and monitoring tumor status.

Receptor tyrosine kinase gene amplification is predictive of intraoperative seizures during glioma resection with functional mapping.

OBJECTIVE: Intraoperative seizures during craniotomy with functional mapping is a common complication that impedes optimal tumor resection and results in significant morbidity. The relationship between genetic mutations in gliomas and the incidence of intraoperative seizures has not been well characterized. Here, the authors performed a retrospective study of patients treated at their institution over the last 12 years to determine whether molecular data can be used to predict the incidence of this complication. METHODS: The authors queried their institutional database for patients with brain tumors who underwent resection with intraoperative functional mapping between 2005 and 2017. Basic clinicopathological characteristics, including the status of the following genes, were recorded: IDH1/2, PIK3CA, BRAF, KRAS, AKT1, EGFR, PDGFRA, MET, MGMT, and 1p/19q. Relationships between gene alterations and intraoperative seizures were evaluated using chi-square and two-sample t-test univariate analysis. When considering multiple predictive factors, a logistic multivariate approach was taken. RESULTS: Overall, 416 patients met criteria for inclusion; of these patients, 98 (24%) experienced an intraoperative seizure. Patients with a history of preoperative seizure and those treated with antiepileptic drugs prior to surgery were less likely to have intraoperative seizures (history: OR 0.61 [95% CI 0.38-0.96], chi-square = 4.65, p = 0.03; AED load: OR 0.46 [95% CI 0.26-0.80], chi-square = 7.64, p = 0.01). In a univariate analysis of genetic markers, amplification of genes encoding receptor tyrosine kinases (RTKs) was specifically identified as a positive predictor of seizures (OR 5.47 [95% CI 1.22-24.47], chi-square = 5.98, p = 0.01). In multivariate analyses considering RTK status, AED use, and either 2007 WHO tumor grade or modern 2016 WHO tumor groups, the authors found that amplification of the RTK proto-oncogene, MET, was most predictive of intraoperative seizure (p < 0.05). CONCLUSIONS: This study describes a previously unreported association between genetic alterations in RTKs and the occurrence of intraoperative seizures during glioma resection with functional mapping. Future models estimating intraoperative seizure risk may be enhanced by inclusion of genetic criteria.

Navigating the Landscape of Tumor Extracellular Vesicle Heterogeneity.

The last decade has seen a rapid expansion of interest in extracellular vesicles (EVs) released by cells and proposed to mediate intercellular communication in physiological and pathological conditions. Considering that the genetic content of EVs reflects that of their respective parent cell, many researchers have proposed EVs as a source of biomarkers in various diseases. So far, the question of heterogeneity in given EV samples is rarely addressed at the experimental level. Because of their relatively small size, EVs are difficult to reliably isolate and detect within a given sample. Consequently, standardized protocols that have been optimized for accurate characterization of EVs are lacking despite recent advancements in the field. Continuous improvements in pre-analytical parameters permit more efficient assessment of EVs, however, methods to more objectively distinguish EVs from background, and to interpret multiple single-EV parameters are lacking. Here, we review EV heterogeneity according to their origin, mode of release, membrane composition, organelle and biochemical content, and other factors. In doing so, we also provide an overview of currently available and potentially applicable methods for single EV analysis. Finally, we examine the latest findings from experiments that have analyzed the issue at the single EV level and discuss potential implications.