Spatially Resolved Near Field Spectroscopy of Vibrational Polaritons at the Small N Limit.

Vibrational polaritons, which have been primarily studied in Fabry-Pérot cavities with a large number of molecules (N ∼ 106-1010) coupled to the resonator mode, exhibit various experimentally observed effects on chemical reactions. However, the exact mechanism is elusively understood from the theoretical side, as the large number of molecules involved in an experimental strong coupling condition cannot be represented completely in simulations. This discrepancy between theory and experiment arises from computational descriptions of polariton systems typically being limited to only a few molecules, thus failing to represent the experimental conditions adequately. To address this mismatch, we used surface phonon polariton (SPhP) resonators as an alternative platform for vibrational strong coupling. SPhPs exhibit strong electromagnetic confinement on the surface and thus allow for coupling to a small number of molecules. As a result, this platform can enhance nonlinearity and slow down relaxation to the dark modes. In this study, we fabricated a pillar-shaped quartz resonator and then coated it with a thin layer of cobalt phthalocyanine (CoPc). By employing scattering-type scanning near-field optical microscopy (s-SNOM), we spatially investigated the dependency of vibrational strong coupling on the spatially varying electromagnetic field strength and demonstrated strong coupling with 38,000 molecules only-reaching to the small N limit. Through s-SNOM analysis, we found that strong coupling was observed primarily on the edge of the quartz pillar and the apex of the s-SNOM tip, where the maximum field enhancement occurs. In contrast, a weak resonance signal and lack of coupling were observed closer to the center of the pillar. This work demonstrates the importance of spatially resolved polariton systems in nanophotonic platforms and lays a foundation to explore polariton chemistry and chemical dynamics at the small N limit-one step closer to reconcile with high-level quantum calculations.

Effects of different step lengths at a preferred walking speed on forefoot, midfoot, and hindfoot motion in healthy young adults.

Hindfoot, midfoot, and forefoot motion during the stance phase of walking provide insights into the forward progression of the body over the feet via the rocker mechanisms. These segmental motions are affected by walking speed. Increases in walking speed are accomplished by increasing step length and cadence. It is unknown if taking short, medium, and long steps at the same speed would increase hindfoot, midfoot, and forefoot motion similarly to walking speed. We examined effects of different step lengths at the same preferred walking speed on peak forefoot, midfoot, and hindfoot motions related to the foot rockers. Twelve young healthy adults completed five walking trials under three step length conditions in a random order as feet and lower extremity motion were measured via marker positions for the combined Oxford foot and conventional gait models. Peak hindfoot, midfoot, and forefoot joint angles indicating heel, ankle, and forefoot rockers were identified. When walking at the same preferred speed with increase in step length, there were increases in peak hindfoot-tibia plantarflexion angle (p < 0.001; ηp2 = 0.76) in early stance associated with the heel rocker and peak hindfoot-tibia dorsiflexion angle (p = 0.016; ηp2 = 0.39) in midstance associated with ankle rocker. In late stance, the peak hindfoot-tibia plantarflexion angle, forefoot-hindfoot angle, and forefoot-hallux dorsiflexion angle indicating forefoot rocker motion also increased with step length (p < 0.01). When foot kinematics are compared across different individuals or the same individual across different sessions, researchers and clinicians should consider the influence of step length as a contributor to differences in foot kinematics observed.

Multiplex Immunofluorescence Staining Protocol for the Dual Imaging of Hypoxia-Inducible Factors 1 and 2 on Formalin-Fixed Paraffin-Embedded Samples.

Hypoxia is a common condition in rapidly proliferating tumors and occurs when oxygen delivery to the tissue is scarce. It is a prevalent feature in ~90% of solid tumors. The family of HIF (hypoxia-inducible factor) proteins-HIF1α and HIF2α-are the main transcription factors that regulate the response to hypoxia. These transcription factors regulate numerous downstream gene targets that promote the aggressiveness of tumors and therefore have been linked to worse prognosis in patients. This makes them a potential biomarker to be tested in the clinical setting to predict patient outcomes. However, HIFs have been notoriously challenging to immunolabel, in part due to their fast turnover under normal oxygen conditions. In this work, we developed a multiplexed immunofluorescence (mIF) staining protocol for the simultaneous detection of HIF1α and HIF2α in the same formalin-fixed paraffin-embedded (FFPE) tissue section.

Staining Hypoxic Areas of Frozen and FFPE Tissue Sections with Hypoxyprobe™.

Hypoxia occurs due to inadequate levels of oxygen in tissue and has been implicated in numerous diseases such as cancer, diabetes, cardiovascular, and neurodegenerative diseases. Hypoxia activates hypoxia-inducible factors (HIF) which mediate the expression of several downstream genes. Within the context of cancer biology, these genes affect cellular processes including metabolism, proliferation, migration, invasion, and metastasis. Pimonidazole hydrochloride (HCl) is an exogenous marker that is reduced and binds to thiols under hypoxic conditions resulting in adducts that can be visualized using antibodies such as Hypoxyprobe™. This chapter describes a method for using Hypoxyprobe™ to detect hypoxic areas in frozen and FFPE mouse samples by immunofluorescence (IF) and immunohistochemistry (IHC) staining.

Intraoperative navigation system use increases accuracy of glenoid component inclination but not functional outcomes in reverse total shoulder arthroplasty: a prospective comparative study.

BACKGROUND: While the use of computer-assisted navigation systems in prosthetic implantation is steadily increasing, its utility in reverse shoulder arthroplasty (RSA) remains unclear. The purpose of this study was to evaluate the clinical utility of an intraoperative navigation system in patients undergoing RSA. MATERIALS AND METHODS: Patients undergoing navigated or standard RSA at a single institution between September 2020 and December 2021 were prospectively enrolled. Exclusion criteria included noncompliance with study procedures or humeral fracture. Outcome measures included postoperative version and inclination, range of motion (ROM), complications, and patient-reported outcome measurements (PROMs: American Shoulder and Elbow Surgeons score [ASES], Disabilities of the Arm, Shoulder, and Hand score [DASH], Simple Shoulder Test [SST], and Visual Analog Scale [VAS]) at final follow-up. RESULTS: The final cohort contained 16 patients with navigation and 17 with standard RSA at a mean follow-up of 16 months (range 12-18 months). Average age was 72 years (range 66-80 years), 8 male (24%) and 25 female (76%). There were no differences in demographics between groups (p > 0.05). At baseline, the navigated group had a greater proportion of Walch B1 and B2 glenoids (p = 0.04). There were no differences between groups regarding baseplate type and native/planned/postoperative glenoid version and inclination. In both groups, planned and postoperative versions were not significantly different (p = 0.76). Patients who did not have navigation demonstrated significant differences between planned and postoperative inclination (p = 0.04), while those with navigation did not (p = 0.09). PROM scores did not differ between groups at final follow-up for SST (p = 0.64), DASH (p = 0.38), ASES (p = 0.77), or VAS (p = 0.1). No difference in final ROM was found between groups (p > 0.05). Over 50% of all screws in both groups were positioned outside the second cortex (p = 0.37), albeit with no complications. CONCLUSIONS: There were no statistically significant differences in ROM, PROMs, and satisfaction between patients receiving computer-navigated and standard RSA at a short-term follow-up. Despite more severe preoperative glenoid erosion in the navigated group, all patients were able to achieve an appropriate neutral axis postoperatively. The cost effectiveness and appropriate use of computer-navigated RSA warrant specific investigation in future studies. LEVEL OF EVIDENCE: II, prospective cohort study. TRIAL REGISTRATION: 9/1/2020 to 12/31/2021.

A Radiostereometric Analysis of Tendon Migration After Arthroscopic and Mini-Open Biceps Tenodesis: Interference Screw Versus Single Suture Anchor Fixation.

BACKGROUND: Studies suggest that similar clinical results are achieved via arthroscopic and open biceps tenodesis (BT) techniques. PURPOSE: To quantify the postoperative migration of the BT construct between arthroscopic suprapectoral BT (ASPBT) and open subpectoral BT (OSPBT) techniques via interference screw (IS) or single-suture suture anchor (SSSA) fixation using radiostereometric analysis. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Distal migration of the biceps tendon after OSPBT with a polyetheretherketone IS, OSPBT with 1 SSSA, ASPBT with polyetheretherketone IS, and ASPBT with 2 SSSAs was measured prospectively. Patients with symptomatic biceps tendinopathy and preoperative patient-reported outcome measures (PROMs) including Constant-Murley subjective, Single Assessment Numeric Evaluation, or Patient-Reported Outcomes Measurement Information System-Upper Extremity scores were included. A tantalum bead was sutured on the proximal end of the long head of the biceps tendon before fixation of tendon tissue. Anteroposterior radiographs were performed immediately postoperatively, at 1 week, and at 3 months. Bead migration was measured, and preoperative PROMs were compared with those at latest follow-up. RESULTS: Of 115 patients, 94 (82%) were available for final follow-up. IS fixation yielded the least tendon migration with no difference between the open and arthroscopic approaches (4.31 vs 5.04 mm; P = .70). Fixation with 1 suture anchor demonstrated significantly greater migration than that achieved with an IS at both 1 week (6.47 vs 0.1 mm, 6.47 vs 1.75 mm, P < .001;) and 3 months (14.76 vs 4.31 mm, 14.76 vs 5.04 mm, P < .001) postoperatively. Two-suture anchor fixation yielded significantly greater migration than IS fixation at 1 week (7.02 vs 0.1 mm, P < .001; 7.02 vs 1.75 mm, P = .003) but not 3 months postoperatively (8.06 vs 4.31 mm, P = .10; 8.06 vs 5.04 mm, P = .07). Four patients with suture anchor fixation (3 patients in the OSPBT 1 SSSA group, 9.4%, and 1 patient in the ASPBT 2 SSSAs group, 3.8%) developed a Popeye deformity, whereas no Popeye deformities occurred in the IS groups. Mean 3-month bead migration in patients with and without a Popeye deformity was 60.8 and 11.2 mm, respectively (P < .0001). PROMs did not differ among groups at final follow-up. CONCLUSION: Interference screw fixation yielded the least tendon migration whether achieved arthroscopically or open. The available data indicated that fixation with 1 SSSA but not 2 SSSAs resulted in significantly greater migration than that achieved with an IS. Despite variations in tendon migration, PROMs were similar among all groups. When SSSAs are used, tendon migration may be minimized by using ≥2 anchors.

Total Knee Arthroplasty After Meniscectomy Is More Likely in Patients With Bicompartmental or Complex Tears.

Purpose: To determine the relationship between meniscus tear morphologies, stratified by location and pattern, and knee arthroplasty rates in a commercial insurance population. Methods: The PearlDiver database was queried for patients ≥35 years old with a meniscus tear of specified laterality and ≥2 years follow-up between 2015 and 2018. Two analyses were conducted with cohorts matched on age, sex, Charlson Comorbidity Index, obesity, osteoarthritis (OA), and treatment (meniscectomy vs conservative): one with equal-sized subgroups by tear location (medial only, lateral only, or both medial and lateral) and another by tear pattern (bucket-handle, complex, or peripheral). The rate of subsequent total knee arthroplasty (TKA) was compared between matched groups. Results: In total, 129,987 patients (mean age: 57.8 ± 10.5 years) were matched by tear location; 1,734 patients with medial-only tears (4.0%), 1,786 with lateral-only tears (4.1%), and 2,611 with medial plus lateral tears (6.0%) underwent a TKA within 5 years (P < .001). Patients with both medial and lateral tears were 1.55-fold more likely to undergo TKA. In total, 24,213 patients (mean age: 56.0 ± 10.5 years) were matched by tear pattern; 296 patients with bucket-handle tears (3.7%), 373 with complex tears (4.6%), and 336 with peripheral tears (4.2%) underwent TKA (P = .01). Patients with complex tears were 1.29-fold more likely to undergo TKA than patients with bucket-handle tears (P = .002). Conclusions: In matched cohorts of patients with degenerative meniscus tears, having both medial plus lateral tears conferred a 1.5-fold risk of TKA, whereas complex tears conferred a 1.3-fold risk within 5 years. Specific meniscal tear patterns and locations harbor varying risk in progressing to end-stage knee OA, and these data may help counsel patients about their likelihood of progressing to end-stage OA warranting an arthroplasty procedure. Level of Evidence: Level III, retrospective comparative study.

Walking in high-heel shoes induces redistribution of joint power and work.

Walking in high-heel shoes (HHS) decreases the push-off power and little research has examined the specific muscle groups that compensate for it. The purpose was to examine the effects of walking in HHS compared to barefoot on lower extremity net joint work and power. Fourteen young women walked in HHS and barefoot at a fixed speed of 1.3 m·s-1. Marker position and ground reaction force data were synchronously measured at 100 and 1000 Hz, respectively. Peak power and joint work variables were computed over the power phases of the gait cycle using an inverse dynamic approach. When walking in HHS was compared to barefoot, participants exerted a diminished push-off characterized by lesser peak power and lesser work by the ankle plantar flexors in late stance (A2 phase; p < 0.001). To compensate for the reduced ankle plantar flexor power, greater peak power was generated and work was performed in early stance by hip extensors (H1 phase; p ≤ 0.001), in mid-stance by knee extensors (K2 phase; p < 0.001) and in late stance and early swing phase by hip flexor muscles (H3 phase; p ≤ 0.001). Walking in HHS induces biomechanical plasticity and causes distal-to-proximal redistribution of net joint power and work during walking.

Study of dry eye syndrome: Focus on causative factors, treatment modalities, quality of life, and preservatives used in eye drops.

Purpose: Dry eye syndrome (DES) is a global issue occurring due to tear deficiency or excessive tear evaporation. It is associated with a variety of symptoms causing ocular discomfort. The purpose of the study was to evaluate causative factors, treatment modalities, quality of life, and preservatives used in eye drops. Methods: This prospective, follow-up study was conducted in the ophthalmology outpatient department of a tertiary care teaching hospital. Patients older than 18 years of age of either sex diagnosed with DES and willing to give written informed consent were included. The patients were subjected to the Ocular surface disease index Questionnaire (OSDI Questionnaire) twice; at the time of the first visit and at 15 days follow-up. Results: A male preponderance was observed with a 1.86:1 male-to-female ratio. The mean age of the study population was 29.15 ± 10.07 years. The most common presenting complaints were symptoms related to dryness of the eyes followed by refractive error. Exposure to TV/computer screen for more than 6 hours is the most common causative factor. There was a statistically significant improvement in overall quality of life (QoL) in patients of DES on treatment. However, no significant difference was seen in the improvement of quality of life in comparison with different preservatives used in prescribed eye drops for the treatment of DES. Conclusion: DES can adversely affect the quality of life of patients. Prompt treatment of this condition can significantly improve the patient's QoL. Physicians should be encouraged to perform quality of life evaluations for patients with DES to guide them in treatment with more individual-specific treatment options.

The effect of EMG biofeedback training on muscle activation in an impingement population.

Subacromial impingement syndrome (SAIS) is one of the most diagnosed causes of pain in the upper extremity. The purpose of this study was to investigate muscle activity between asymptomatic and SAIS shoulders on the same subject while understanding the effectiveness of EMG biofeedback training (EBFB) on bilateral overhead movements. Ten participants (7 male), that tested positive for 2/3 SAIS clinical tests, volunteered for the study. Bilateral muscle activity was measured via electrodes on the upper trapezius (UT), lower trapezius (LT), serratus anterior (SA), and lumbar paraspinals (LP). Participants performed bilateral scapular plane overhead movements before and after EBFB. EBFB consisted of 10 bilateral repetitions of I, W, T, and Y exercises focused on reducing UT and increasing LT and SA activity. Prior to EBFB, no significant difference in muscle activity was present between sides. A significant main effect of time indicated that after EBFB both sides exhibited reduced UT activity at 60° (p = 0.003) and 90° (p = 0.036), LT activity was increased at all measured humeral angles (p < 0.0005), and SA muscle activity was increased at 110° (p = 0.001). EBFB in conjunction with scapular based exercise effectively alters muscle activity of asymptomatic and symptomatic scapular musculature.

Predictive factors and visual outcomes after immediate pars plana vitrectomy for posteriorly dislocated lens fragments during complicated phacoemulsification surgery.

Purpose: To investigate the prognostic factors for visual outcome in patients undergoing immediate pars plana vitrectomy (PPV) for posteriorly dislocated lens fragments during phacoemulsification surgery. Methods: This was a single-center, retrospective, cross-sectional study of 37 eyes of 37 patients undergoing immediate PPV for posteriorly dislocated lens fragments from 2015 to 2021. The primary outcome measure was changes in the best-corrected visual acuity (BCVA). Additionally, we analyzed the predictive factors for poor visual outcomes (BCVA <20/40) and perioperative complications. Results: The mean (±standard deviation [SD]) age of the patients was 66.57 (±10.86) years, with an almost identical gender profile (M: F = 18/19 [48.64%:51.36%]). The median (interquartile range [IQR]) log of minimum angle of resolution (logMAR) BCVA improved significantly from the baseline (1 [0.6-1.48], ~20/200) to the final visit (0.3 [0.2-0.6], ~20/40) (P < 0.0001) after a mean (±SD) follow-up of 6.35 (±6.32) months. The final BCVA was 20/40 or better in 59.5% of the eyes. Poor final BCVA (<20/40) was associated with small preoperative pupillary size (P = 0.02), presence of preoperative ocular pathology (P = 0.02) including uveitis, glaucoma, and clinically significant macular edema (CSME), intraoperative displacement of >50% of lens matter into the vitreous (P < 0.001), use of iris-claw lens (P < 0.001), and postoperative cystoid macular edema (CME; P = 0.007). The postoperative complications included CME (13.51%), retinal detachment (10.81%), chronic uveitis (8.11%), glaucoma (8.11%), iritis (2.7%), posterior chamber IOL (PCIOL) dislocation (2.7%), and vitreous hemorrhage (2.7%). Conclusion: For retained lens fragments in complicated phacoemulsification surgery, immediate PPV is a viable approach with the potential for a good visual outcome. The important predictors for poor visual outcomes include a small preoperative pupil size, preexisting ocular pathology, displacement of significant volume of lens matter (>50%), use of an iris-claw lens, and CME.

The epidemiology and disease pattern of pediatric ocular morbidities in Western India: The National Institute of OphthalMology AmBlyopia StUdy in Indian Paediatric EyeS (NIMBUS) study report 1.

Purpose: To determine the pattern of pediatric ocular morbidities in western India. Methods: This was a retrospective longitudinal study that included all consecutive children aged ≤15 years who presented to the outpatient department of a tertiary eye center for the first time. Patient demographics, best-corrected visual acuity (BCVA), and ocular examination data were compiled. Subgroup analysis was also performed based on age group (years): ≤5, 5-10, and >10-15. Results: A total of 11,126 eyes of 5563 children were included in the study. The mean age of the study population was 5.15 (±3.32) years with males (57.07%) being predominant. Approximately half of the patients (50.19%) were under the age of 5 years, followed by those aged 5-10 years (45.1%) and >10-15 years (4.71%). Among the study eyes, the BCVA was ≥20/60 in 58.57%, indeterminable in 35.16%, and <20/60 in 6.71%. The commonest ocular morbidity noted was refractive error (28.97%) followed by allergic conjunctivitis (7.64%) and strabismus (4.95%) in the total study cohort and also after age stratification. Conclusion: Refractive error, allergic conjunctivitis, and strabismus are the major causes of ocular morbidity in pediatric eyes at a tertiary care center. Planning screening programs at the regional and national levels is crucial to decreasing the burden of eye disorders. These programs also need to have a suitable referral mechanism established and be smoothly connected to primary and secondary health-care centers. This will help to assure quality eye care delivery, while also reducing the strain of overworked tertiary centers.

Quadriceps Weakness is Associated with Neuroplastic Changes Within Specific Corticospinal Pathways and Brain Areas After Anterior Cruciate Ligament Reconstruction: Theoretical Utility of Motor Imagery-Based Brain-Computer Interface Technology for Rehabilitation.

Persistent quadriceps weakness is a problematic sequela of anterior cruciate ligament reconstruction (ACLR). The purposes of this review are to summarize neuroplastic changes after ACL reconstruction; provide an overview of a promising interventions, motor imagery (MI), and its utility in muscle activation; and propose a framework using a brain-computer interface (BCI) to augment quadriceps activation. A literature review of neuroplastic changes, MI training, and BCI-MI technology in postoperative neuromuscular rehabilitation was conducted in PubMed, Embase, and Scopus. Combinations of the following search terms were used to identify articles: "quadriceps muscle," "neurofeedback," "biofeedback," "muscle activation," "motor learning," "anterior cruciate ligament," and "cortical plasticity." We found that ACLR disrupts sensory input from the quadriceps, which results in reduced sensitivity to electrochemical neuronal signals, an increase in central inhibition of neurons regulating quadriceps control and dampening of reflexive motor activity. MI training consists of visualizing an action, without physically engaging in muscle activity. Imagined motor output during MI training increases the sensitivity and conductivity of corticospinal tracts emerging from the primary motor cortex, which helps "exercise" the connections between the brain and target muscle tissues. Motor rehabilitation studies using BCI-MI technology have demonstrated increased excitability of the motor cortex, corticospinal tract, spinal motor neurons, and disinhibition of inhibitory interneurons. This technology has been validated and successfully applied in the recovery of atrophied neuromuscular pathways in stroke patients but has yet to be investigated in peripheral neuromuscular insults, such as ACL injury and reconstruction. Well-designed clinical studies may assess the impact of BCI on clinical outcomes and recovery time. Quadriceps weakness is associated with neuroplastic changes within specific corticospinal pathways and brain areas. BCI-MI shows strong potential for facilitating recovery of atrophied neuromuscular pathways after ACLR and may offer an innovative, multidisciplinary approach to orthopaedic care. Level of Evidence: V, expert opinion.

Mebendazole Treatment Disrupts the Transcriptional Activity of Hypoxia-Inducible Factors 1 and 2 in Breast Cancer Cells.

Breast cancer is the most diagnosed cancer in women in the world. Mebendazole (MBZ) has been demonstrated to have preclinical efficacy across multiple cancers, including glioblastoma multiforme, medulloblastoma, colon, breast, pancreatic, and thyroid cancers. MBZ was also well tolerated in a recent phase I clinical trial of adults diagnosed with glioma. The mechanisms of action reported so far for MBZ include tubulin disruption, inhibiting angiogenesis, promoting apoptosis, and maintaining stemness. To elucidate additional mechanisms of action for mebendazole (MBZ), we performed RNA sequencing of three different breast cancer cell lines treated with either MBZ or vehicle control. We compared the top genes downregulated upon MBZ treatment with expression profiles of cells treated with over 15,000 perturbagens using the clue.io online analysis tool. In addition to tubulin inhibitors, the gene expression profile that correlated most with MBZ treatment matched the profile of cells treated with known hypoxia-inducible factor (HIF-1α and -2α) inhibitors. The HIF pathway is the main driver of the cellular response to hypoxia, which occurs in solid tumors. Preclinical data support using HIF inhibitors in combination with standard of care to treat solid tumors. Therefore, we tested the hypothesis that MBZ could inhibit the hypoxia response. Using RNA sequencing and HIF-reporter assays, we demonstrate that MBZ inhibits the transcriptional activity of HIFs in breast cancer cell lines and in mouse models of breast cancer by preventing the induction of HIF-1α, HIF-2α, and HIF-1ß protein under hypoxia. Taken together, our results suggest that MBZ treatment has additional therapeutic efficacy in the setting of hypoxia and warrants further consideration as a cancer therapy.

Enabling multiple intercavity polariton coherences by adding quantum confinement to cavity molecular polaritons.

In this study, the "particle in a box" idea, which was broadly developed in semiconductor quantum dot research, was extended into mid-infrared (IR) cavity modes by applying lateral confinement in an optical cavity. The discrete cavity modes hybridized with molecular vibrational modes, resulting in a quartet of polariton states that can support multiple coherence states in the IR regime. We applied tailored pump pulse sequences to selectively prepare these coherences and verified the multi-coherence existence. The simulation based on Lindblad equation showed that because the quartet of polariton states resided in the same cavity, they were specifically robust toward decoherence caused by fluctuations in space. The multiple robust coherences paved the way for entangled states and coherent interactions between cavity polaritons, which would be critical for advancing polariton-based quantum information technology.

Reverse Total Shoulder Arthroplasty Demonstrates Better Outcomes Than Angular Stable Plate in the Treatment of Three-part and Four-part Proximal Humerus Fractures in Patients Older Than 70 Years.

BACKGROUND: Proximal humeral fractures are traditionally treated with open reduction and internal fixation (ORIF), but reverse total shoulder arthroplasty (RTSA) has emerged as an increasingly popular treatment option. Although ORIF with angular locking plates is a common treatment for proximal humerus fractures, prior reports suggest high failure and complication rates. Although RTSA has become an increasingly popular option for complex proximal humeral head fractures given its low complication rates, there are concerns it may lead to limited postoperative ROM. Thus, the optimal treatment for patients older than 70 years from a functional and radiographic perspective remains unclear. QUESTIONS/PURPOSES: (1) In patients older than 70 years with three-part and four-part proximal humerus fractures, does RTSA result in better functional outcome scores (Constant, American Shoulder and Elbow Surgeons [ASES], and DASH scores) than ORIF with a locking plate? (2) Does RTSA result in greater ROM than ORIF? (3) Does RTSA result in a lower risk of complications than ORIF? (4) In patients with either procedure, what are the rates of negative radiographic outcomes in those treated with ORIF (such as malunion, bone resorption, malalignment, or avascular necrosis) or those with RTSA (such as resorption, notching, and loosening)? (5) At a minimum of 2 years of follow-up, does ORIF result in a greater number of revision procedures than RTSA? METHODS: Between January 1, 2013, and June 30, 2018, we treated 235 patients for a proximal humeral fracture. We considered only patients without previous ipsilateral fracture or surgery, other fractures, or radial nerve injuries; age older than 70 years; and patients without neurologic disease or cognitive dysfunction as potentially eligible. Sixty-nine percent (162 patients) of the patients were eligible; a further 31% (73 patients) were excluded because 18% (13 of 73 patients) did not meet the inclusion criteria, 62% (45 patients) underwent nonoperative treatment, and 21% (15 patients) declined to participate. Patients were nonrandomly allocated to receive RTSA if they had supraspinatus Goutallier/Fuchs Grade 3 or 4 atrophy or ORIF if they had supraspinatus Goutallier/Fuchs Grade 1 or 2 atrophy. This left 81 patients who were treated with RTSA and another 81 patients who were treated with ORIF. Among the 81 patients treated with RTSA, 11% (nine patients) were lost to the minimum study follow-up of 2 years or had incomplete datasets, leaving 89% (72 patients) for analysis. Among the 81 patients treated with ORIF, 19% (15 patients) were lost before the minimal study follow-up of 2 years or had incomplete datasets, leaving 82% (66 patients) for analysis. The median follow-up for both groups was 53 months (range 24 to 72 months). The mean age was 76 ± 2.9 years in the RTSA group and 73 ± 2.9 years in the ORIF group. In the RTSA group, 27 patients had a three-part fracture and 45 patients had a four-part fracture. In the ORIF group, 24 patients had three-part fractures and 42 patients had four-part fractures (p = 0.48). Shoulder function was assessed using functional outcome questionnaires (ASES, DASH, and Constant) and active ROM measurements. A surgical complication was defined as any instance of dislocations, fractures, adhesive capsulitis, nerve injuries, or surgical site infections. Radiographic outcomes after ORIF (malunion, tuberosity resorption, or avascular necrosis) and RTSA (notching and osteolysis) were assessed. In calculating the revision rate, we considered unplanned revision procedures only. RESULTS: Compared with patients treated with ORIF, patients treated with RTSA had superior improvements in Constant (85.0 ± 7.0 versus 53.0 ± 5.0; mean difference 32 [95% CI 30 to 34]; p < 0.01), ASES (46.3 ± 3.7 versus 30.0 ± 3.5; mean difference 16 [95% CI 15 to 18]; p < 0.01), and DASH scores (40.5 ± 4.2 versus 30.5 ± 2.6; mean difference 10 [95% CI 9 to 11]; p < 0.01). The mean elevation was 135° ± 7° for patients with RTSA and 100° ± 6° for patients with ORIF (mean difference 35 o [95% CI 33 to 37]; p < 0.01). The mean abduction was 131° ± 7° for patients with RTSA and 104° ± 6° for those with ORIF (mean difference 27 o [95% CI 25° to 29°]; p < 0.01). The mean external rotation was 85° ± 5° for patients with RTSA and 64° ± 5° for those with ORIF (mean difference 21° [95% CI 19° to 23°]; p < 0.01). The mean internal rotation was 45° ± 6° for patients with RTSA and 40° ± 6° for those with ORIF (mean difference 5° [95% CI 3° to 7°]; p < 0.01). The risk of complications was not different between patients with ORIF and those with RTSA (5% [three of 66] versus 1% [one of 72]; relative risk 3.3 [95% CI 0.3 to 30.7]; p = 0.30). Among patients with ORIF, 8% had varus malunions (five of 66), 6% had resorption of the greater tuberosity (four of 66), and 2% had avascular necrosis of the humeral head (one of 66). In the RTSA group, 24% (17 of 72 patients) demonstrated reabsorption of periprosthetic bone and 79% of patients (57 of 72) exhibited no notching. The risk of revision was not different between the RTSA and ORIF groups (0% [0 of 72] versus 9% [six of 66]; relative risk 0.07 [95% CI 0.0 to 1.2]; p = 0.07). CONCLUSION: In patients older than 70 years with three-part and four-part proximal humerus fractures, primary RTSA resulted in better patient-reported outcome scores and better ROM than ORIF with an angular stable locking plate. Our findings might help surgeons decide between internal fixation and arthroplasty to surgically treat these injuries in older patients. Although RTSA seems to be a preferable treatment modality in view of these findings, longer follow-up is required to evaluate its longevity compared with ORIF with an angular locking plate. Dissimilar to ORIF, which is generally stable once healed, arthroplasties are at a continued risk for loosening and infection even after healing is complete. LEVEL OF EVIDENCE: Level II, therapeutic study.

The Epidemiology of Platelet-Rich Plasma Injections From 2010 to 2020 in a Large US Commercial Insurance Claims Database: A Recent Update.

INTRODUCTION: The popularity of platelet-rich plasma (PRP) injections for the treatment of orthopaedic conditions has grown markedly. We sought to better define the trends in the usage of orthopaedic PRP injections across an insured US population over the past decade. METHODS: The PearlDiver M91Ortho commercial administrative claims database was queried for all patients receiving PRP injections for orthopaedic conditions from 2010 through the first quarter of 2020 (Q1.2020). Trends in PRP use, reimbursement charges, demographics, joints injected, and administering physicians were assessed over time and reported as year-over-year (YOY) changes. RESULTS: Over the study period, 14,096 unique patients had 17,759 orthopaedic PRP injections. The number of PRP injections administered had a YOY increase of 7.1% (144 injections/year, 95% confidence interval [CI] = 89 to 199, Ptrend = 0.0009). A YOY increase of 895% was observed in total nonsurgical charges ($683,974/yr, 95% CI 441,504 to 926,444, Ptrend = 0.0009). The median age of PRP recipients increased (YOY change = +0.6 years, 95% CI 0.4 to 0.8, Ptrend = 0.0005). Injections to the elbow (YOY change = -0.8%, 95% CI -0.10% to [-0.06%], Ptrend = 0.005) and foot/ankle (YOY change = -1.0%, 95% CI -1.4% to [-0.06%], Ptrend = 0.002) decreased, whereas hip (YOY change = +0.4%, 95% CI 0.2% to 0.6%, Ptrend = 0.019), knee (YOY change = +0.9%, 95% CI 0.3% to 1.2%, Ptrend = 0.016), and spine (YOY change = +0.2%, 95% CI 0.0% to 0.4%, Ptrend = 0.033) injections increased. PRP injections given by sports medicine orthopaedic surgeons (YOY change = +0.8%, 95% CI 0.6% to 1.2%, Ptrend <0.0001) increased over time, whereas those by general orthopaedic surgeons decreased (YOY change = -0.9, 95% CI -1.2 to [-0.6%], Ptrend = 0.001). CONCLUSION: PRP injections quadrupled in prevalence from 2010 to Q1.2020, with a projected increase in annual usage in this data set of 66% by 2030. As greater evidence-based indications for PRP use are identified, more specialists and insurance providers may consider expanding their involvement in this growing field. LEVEL OF EVIDENCE: III, retrospective cohort study.

Mebendazole prevents distant organ metastases in part by decreasing ITGß4 expression and cancer stemness.

Breast cancer is the most diagnosed cancer among women. Approximately 15-20% of all breast cancers are highly invasive triple-negative breast cancer (TNBC) and lack estrogen, progesterone, and ERBB2 receptors. TNBC is challenging to treat due to its aggressive nature with far fewer targeted therapies than other breast cancer subtypes. Current treatments for patients with TNBC consist of cytotoxic chemotherapies, surgery, radiation, and in some instances PARP inhibitors and immunotherapy. To advance current therapeutics, we repurposed mebendazole (MBZ), an orally available FDA-approved anthelmintic that has shown preclinical efficacy for cancers. MBZ has low toxicity in humans and efficacy in multiple cancer models including breast cancer, glioblastoma multiforme, medulloblastoma, colon cancer, pancreatic and thyroid cancer. MBZ was well-tolerated in a phase I clinical trial of adults recently diagnosed with glioma. We determined that the half-maximal inhibitory concentration (IC50) of MBZ in four breast cancer cell lines is well within the range reported for other types of cancer. MBZ reduced TNBC cell proliferation, induced apoptosis, and caused G2/M cell cycle arrest. MBZ reduced the size of primary tumors and prevented lung and liver metastases. In addition, we uncovered a novel mechanism of action for MBZ. We found that MBZ reduces integrin ß4 (ITGß4) expression and cancer stem cell properties. ITGß4 has previously been implicated in promoting "cancer stemness," which may contribute to the efficacy of MBZ. Collectively, our results contribute to a growing body of evidence suggesting that MBZ should be considered as a therapeutic to slow tumor progression and prevent metastasis.

Posterior Humeral Avulsion of the Glenohumeral Ligament: A Critical Analysis Review.

➢: Posterior humeral avulsions of the inferior glenohumeral ligament represent an increasingly recognized but likely underdiagnosed source of posterior shoulder instability and pain. ➢: Injuries are commonly reported in athletic individuals who have sustained injury by either traumatic or atraumatic mechanisms; the ligament is most susceptible to injury with the shoulder in flexion, adduction, and internal rotation. ➢: Posterior humeral avulsions of the glenohumeral ligament often occur in the setting of concurrent injuries to the posterior or inferior labrum. ➢: Diagnosis is often challenging due to nonspecific symptoms and physical examination findings; a magnetic resonance arthrogram generally is utilized to identify avulsion from the humeral attachment; however, a definitive diagnosis is often made at the time of arthroscopic evaluation. ➢: In patients with persistent discomfort and limitations following nonoperative management, operative fixation, primarily utilizing arthroscopic techniques, can be performed to restore motion and glenohumeral stability.

Increased Readmission Rates but No Difference in Complication Rates in Patients Undergoing Inpatient Versus Outpatient Hip Arthroscopy: A Large Matched-Cohort Insurance Database Analysis.

Purpose: To compare the early postoperative outcomes of patients undergoing inpatient versus outpatient hip arthroscopy and identify any characteristics that may serve as predictors of these complications. Methods: The PearlDiver Mariner insurance database was queried for all patients who underwent hip arthroscopy from 2010 to 2019. Patients were matched based on Charlson Comorbidity Index, age, and sex. Outcomes recorded included postoperative complications and return to care within 90 days. Predictors of complications were assessed via multivariable logistic regression controlling for age, sex, Charlson Comorbidity Index, comorbidities, surgical setting, and procedure type. Results: The final matched cohort included 832 inpatients and 1,356 matched patients. Fifty-eight patients (7.0%) who underwent inpatient surgery versus 25 patients (1.8%) who underwent outpatient surgery were readmitted (P < .01). Of the readmitted patients, 31 inpatients (3.7%) and 5 outpatients (0.4%) were readmitted for hip-related reasons (P < .01). No significant differences were observed in emergency department visits (67 inpatients [8.1%] vs 84 outpatients [6.2%], P = .11), intensive care unit admissions (3 [0.4%] vs 1 [0.1%], P = .31), or revision hip arthroscopies (43 [5.2%] vs 65 [4.8%], P = .77). A multivariable model of complications correcting for baseline differences in chronic obstructive pulmonary disease, coronary artery disease, diabetes, hypertension, ischemic heart disease, tobacco use, and inpatient status found that age (adjusted odds ratio [OR], 0.92; 95% confidence interval [CI], 0.85-0.99; P = .03), coronary artery disease (adjusted OR, 12.82; 95% CI, 1.18-140.02; P = .03), and inpatient setting (adjusted OR, 20.59; 95% CI, 3.48-401.65; P = .01) were significantly associated with complications. No procedure type was associated with complication rates. Conclusions: Compared with the outpatient setting, inpatient hip arthroscopy is associated with higher rates of readmission in a cohort matched for age, sex, and comorbidities. Complications after inpatient hip arthroscopy appear to be related to comorbidities rather than procedure-related factors. The decision to conduct an inpatient hip arthroscopy should prioritize consideration of patient comorbidities over the type of procedure. Level of Evidence: Level III, retrospective cohort study.