High Delta Angle after Reverse Total Shoulder Arthroplasty increases stresses of the acromion: Biomechanical study of different implant positions.

BACKGROUND: Acromial fractures after Reverse Total Shoulder Arthroplasty (RTSA) are a common complication. Nevertheless, only a few studies have identified risk factors for acromial fractures after RTSA. High delta angle (combination of inferiorization and medialization of the center of rotation) after RTSA was identified as a risk factor in recent studies. The aim of this study was the biomechanical exploration of different delta angles and implant configurations with regard to the acromial stress. METHODS: In a rigid body model of the upper extremity muscle, forces of the deltoid muscle were calculated before and after implanting RTSA in different arm and implant positions. The deltoid muscle was divided into an anterior, middle, and posterior part. Implant positions of the glenoid components were changed in the medialization, lateralization and inferiorization of the center of rotation (COR) as well as lateralization of the humeral component. Further, in a finite element model of the upper extremity, the stresses of the acromion in the same implant design configurations were measured. RESULTS: Differences in acromial stress between different delta angle model configurations were observed. Lateralization (5 mm, 10 mm) of the glenosphere reduced maximal acromial stress by 21% (1.5 MPa) and 31% (1.3 MPa), respectively. Inferiorization (5 mm, 10 mm) of the glenosphere increased maximal acromial stress by 5% (2.0 MPa) and 15% (2.2MPa), respectively. Changes in positioning the humeral component was found to have the highest impact in this model configuration. A 10 mm lateralized humeral component reduced acromial stress by 37% (1.2 MPa) while in the 6 mm medialized configuration, an increase in acromial stress by 83% (3.48 MPa) was observed. There was a high correlation between delta angle and acromial stress (R-squared = 0.967). CONCLUSION: Implant design configuration has an impact on the acromial stress. High delta angles correlate with an increase in acromial stress. Both lateralization of the COR and the humerus decreased the acromial stress in our study. The lateralization of the humerus has the highest impact in influencing acromial stress. Due to contrary results in the current literature, further studies with focus on the acromial stress influenced by different anatomical variants of the shoulder and the acromion are needed before a clinical recommendation can be made.

Hypersensitive quantification of major astringency markers in food and wine by substoichiometric quenching of silicon-rhodamine conjugates.

Tannins are chemically diverse polyphenols in plant-derived products that not only show diverse biological activities but also play a crucial role in determining the sensory attributes of food and beverages. Therefore, their accurate and cost-effective quantification is essential. Here, we identified a novel fluorescence quenching mechanism of different synthetic rhodamine fluorophores, with a high selectivity towards tannic acid (TA) and catechin-3-gallate (C3G) compared to a structurally diverse panel of tannins and polyphenols. Specific chemical conjugates of silicon-rhodamine with alkyl linkers attached to bulky apolar moieties had a limit of detection near 500 pM and a linear range spanning 5-100 nM for TA. We validated the assay on 18 distinct red wine samples, which showed high linearity (R2 = 0.92) with methylcellulose precipitation with no interference from anthocyanins. In conclusion, a novel assay was developed and validated that allows the sensitive and selective quantification of major astringency markers abundant in food and beverages.

Poly(ADP-Ribose) Polymerases-Inhibitor Talazoparib Inhibits Muscle Atrophy and Fatty Infiltration in a Tendon Release Infraspinatus Sheep Model: A Pilot Study.

Structural muscle changes, including muscle atrophy and fatty infiltration, follow rotator cuff tendon tear and are associated with a high repair failure rate. Despite extensive research efforts, no pharmacological therapy is available to successfully prevent both muscle atrophy and fatty infiltration after tenotomy of tendomuscular unit without surgical repair. Poly(ADP-ribose) polymerases (PARPs) are identified as a key transcription factors involved in the maintenance of cellular homeostasis. PARP inhibitors have been shown to influence muscle degeneration, including mitochondrial hemostasis, oxidative stress, inflammation and metabolic activity, and reduced degenerative changes in a knockout mouse model. Tenotomized infraspinatus were assessed for muscle degeneration for 16 weeks using a Swiss Alpine sheep model (n = 6). All sheep received daily oral administration of 0.5 mg Talazoparib. Due to animal ethics, the treatment group was compared with three different controls from prior studies of our institution. To mitigate potential batch heterogeneity, PARP-I was evaluated in comparison with three distinct control groups (n = 6 per control group) using the same protocol without treatment. The control sheep were treated with an identical study protocol without Talazoparib treatment. Muscle atrophy and fatty infiltration were evaluated at 0, 6 and 16 weeks post-tenotomy using DIXON-MRI. The controls and PARP-I showed a significant (control p < 0.001, PARP-I p = 0.01) decrease in muscle volume after 6 weeks. However, significantly less (p = 0.01) atrophy was observed in PARP-I after 6 weeks (control 1: 76.6 ± 8.7%; control 2: 80.3 ± 9.3%, control 3: 73.8 ± 6.7% vs. PARP-I: 90.8 ± 5.1% of the original volume) and 16 weeks (control 1: 75.7 ± 9.9; control 2: 74.2 ± 5.6%; control 3: 75.3 ± 7.4% vs. PARP-I 93.3 ± 10.6% of the original volume). All experimental groups exhibited a statistically significant (p < 0.001) augmentation in fatty infiltration following a 16-week period when compared to the initial timepoint. However, the PARP-I showed significantly less fatty infiltration (p < 0.003) compared to all controls (control 1: 55.6 ± 6.7%, control 2: 53.4 ± 9.4%, control 3: 52.0 ± 12.8% vs. PARP-I: 33.5 ± 8.4%). Finally, a significantly (p < 0.04) higher proportion and size of fast myosin heavy chain-II fiber type was observed in the treatment group. This study shows that PARP-inhibition with Talazoparib inhibits the progression of both muscle atrophy and fatty infiltration over 16 weeks in retracted sheep musculotendinous units.

CBA (4-chloro-2-(2-chlorophenoxy)acetamido) benzoic acid) inhibits TMEM206 mediated currents and TMEM206 does not contribute to acid-induced cell death in colorectal cancer cells.

Introduction: Upon activation at low pH, TMEM206 conducts Cl- ions across plasma and vesicular membranes. In a (patho)physiological context, TMEM206 was reported to contribute to acid-induced cell death in neurons, kidney and cervical epithelial cells. We investigated the role of TMEM206 in acid-induced cell death in colorectal cancer cells. In addition, we studied CBA as a new small molecule inhibitor for TMEM206. Methods: The role of TMEM206 in acid-induced cell death was studied with CRISPR/Cas9-mediated knockout and FACS analysis. The pharmacology of TMEM206 was determined with the patch clamp technique. Results: In colorectal cancer cells, TMEM206 is not a critical mediator of acid-induced cell death. CBA is a small molecule inhibitor of TMEM206 (IC50 = 9.55 µM) at low pH, at pH 6.0 inhibition is limited. Conclusion: CBA demonstrates effective and specific inhibition of TMEM206; however, its inhibitory efficacy is limited at pH 6.0. Despite this limitation, CBA is a potent inhibitor for functional studies at pH 4.5 and may be a promising scaffold for the development of future TMEM206 inhibitors.

Clinical and radiographic long-term outcomes of hemiarthroplasty for complex proximal humeral fractures.

BACKGROUND: Hemiarthroplasty (HA) is a treatment option for complex proximal humeral fractures not suitable for conservative treatment or open reduction-internal fixation. Long-term outcomes using a large-metaphyseal volume prosthesis in the management of proximal humeral fractures have not been reported thus far. METHODS: Between 2006 and 2010, 41 patients with proximal humeral fractures were treated with HA at our institution (average age, 62 years; age range, 38-85 years). Nine patients underwent revision surgery, 3 were lost to follow-up, and 7 died unrelated to the index surgical procedure. Twenty-two patients were reviewed clinically and radiographically after a mean period of 10.4 years (range, 9-13 years). RESULTS: Of the 9 HA failures, 7 occurred within the first 2 postoperative years: 2 patients had infections and 5 had greater tuberosity nonunions or malunions. The other 2 patients underwent revision for rotator cuff deficiency >5 years after initial surgery. Among the patients available for final follow-up, the implant survival rate was 71% (22 of 31 patients). At final follow-up, these patients showed a mean relative Constant score of 76% (range, 49%-96%), mean active elevation of 116° (range, 60°-170°), and mean external rotation of 28° (range, 0°-55°). The majority had good or excellent internal rotation, with internal rotation to the 12th thoracic vertebra in 13 patients (59%) and to the eighth thoracic vertebra in 7 (31%). The mean Subjective Shoulder Value was 76% (range, 40%-100%). Clinical outcomes did not significantly deteriorate over a period of 10 years, except for flexion (P < .001) and internal rotation (P = .002). On analysis of greater tuberosity healing, 1 patient had a nonunion and 10 patients (45%) had a malunion, whereas the greater tuberosity had healed in an anatomic position in 12 patients (55%). Patients with a displaced malunion of the greater tuberosity did not have inferior clinical results at last follow-up. Only 2 patients showed glenoid erosion, and in no patients could stem loosening be identified at final follow-up. CONCLUSION: The revision rate following large-metaphyseal volume HA to treat a proximal humeral fracture was 29% after 10 years postoperatively, with failure within 2 years largely related to greater tuberosity nonunion or malunion and failure later related to rotator cuff insufficiency. Patients with a retained implant showed good clinical and radiographic long-term results, without relevant deterioration over time even when the greater tuberosity healed in a nonanatomic position.

Computer-assisted planning vs. conventional surgery for the correction of symptomatic mid-shaft clavicular nonunion and malunion.

Background: The aim of this study was to compare the clinical and radiographic outcomes of treatment of symptomatic mal- and/or nonunion of midshaft clavicle fractures using radiographically based free-hand open reduction and internal fixation (ORIF) or computer-assisted 3D-planned, personalized corrective osteotomies performed using patient-specific instrumentation (PSI) and ORIF. The hypotheses were that (1) patients treated with computer-assisted planning and PSI would have a better clinical outcome, and (2) computer-assisted surgical planning would achieve a more accurate restoration of anatomy compared to the free-hand technique. Methods: Between 1998 and 2020, 13 patients underwent PSI, and 34 patients underwent free-hand ORIF and/or corrective osteotomy. After application of exclusion criteria, 12/13 and 11/34 patients were included in the study. The clinical examination included measurement of the active range of motion and assessment of the absolute and relative Constant-Murley Scores and the subjective shoulder value. Subjective satisfaction with the cosmetic result was assessed on a Likert scale from 0 to 100 (subjective aesthetic value). 11/13 and 6/11 patients underwent postoperative computed tomography evaluation of both clavicles. Computed tomography scans were segmented to generate 3D surface models. After projection onto the mirrored contralateral side, displacement analysis was performed. Finally, bony union was documented. The average follow-up time was 43 months in the PSI and 50 months in the free-hand cohort. Results: The clinical outcomes of both groups did not differ significantly. Median subjective shoulder value was 97.5% (70; 100) in the PSI group vs. 90% (0; 100) in the free-hand group; subjective aesthetic value was 86.4% (±10.7) vs. 75% (±18.7); aCS was 82.3 (±10.3) points vs. 74.9 (±26) points; and rCS was 86.7 (±11.3) points vs. 81.9 (±28.1) points. In the free-hand group, 2/11 patients had a postoperative neurological complication. In the PSI cohort, the 3D angle deviation was significantly smaller (PSI/planned vs. free-hand/contralateral: 10.8° (3.1; 23.8) vs. 17.4° (11.6; 42.4); P = .020)). There was also a trend toward a smaller 3D shift, which was not statistically significant (PSI/planned vs. free-hand/contralateral: 6 mm (3.4; 18.3) vs. 9.3 mm (5.1; 18.1); P = .342). There were no other significant differences. A bony union was achieved in all cases. Conclusion: Surgical treatment of nonunion and malunions of the clavicle was associated with very good clinical results and a 100% union rate. This study, albeit in a relatively small cohort with a follow-up of 4 years, could not document any clinically relevant advantage of 3D planning and personalized operative templating over conventional radiographic planning and free-hand surgical fixation performed by experienced surgeons.

Rotator Cuff Repair and Overlay Augmentation by Direct Interlocking of a Nonwoven Polyethylene Terephthalate Patch Into the Tendon: Evaluation in an Ovine Model.

BACKGROUND: Arthroscopic repair of large rotator cuff tendon tears is associated with high rates of retear. Construct failure often occurs at the suture-tendon interface. Patch augmentation can improve mechanical strength and healing at this interface. PURPOSE: To introduce a novel technique for suture-free attachment of an overlaid patch and evaluate its biomechanical strength and biological performance. STUDY DESIGN: Descriptive and controlled laboratory studies. METHODS: An established ovine model of partial infraspinatus tendon resection and immediate repair was used. After a nonwoven polyethylene terephthalate patch was overlaid to the resected tendon, a barbed microblade was used to draw fibers of the patch directly into the underlying tissue. In vivo histological assessment of healing was performed at 6 and 13 weeks after implantation. Ex vivo models were used to characterize primary repair strength of the suture-free patch fixation to tendon. Additional ex vivo testing assessed the potential of the technique for patch overlay augmentation of suture-based repair. RESULTS: The in vivo study revealed no macroscopic evidence of adverse tissue reactions to the interlocked patch fibers. Histological testing indicated a normal host healing response with minimal fibrosis. Uniform and aligned tissue ingrowth to the core of the patch was observed from both the tendon and the bone interfaces to the patch. There was no evident retraction of the infraspinatus muscle, lengthening of the tendon, or tendon gap formation over 13 weeks. Ex vivo testing revealed that direct patch interlocking yielded tendon purchase equivalent to a Mason-Allen suture (150 ± 58 vs 154 ± 49 N, respectively; P = .25). In an overlay configuration, fiber interlocked patch augmentation increased Mason-Allen suture retention strength by 88% (from 221 ± 43 N to 417 ± 86 N; P < .01) with no detectable difference in repair stiffness. CONCLUSION: Testing in an ovine model of rotator cuff tendon repair suggested that surgical interlocking of a nonwoven medical textile can provide effective biomechanical performance, support functional tissue ingrowth, and help avoid musculotendinous retraction after surgical tendon repair. CLINICAL RELEVANCE: The novel technique may facilitate patch augmentation of rotator cuff repairs.

Structural Musculotendinous Parameters That Predict Failed Tendon Healing After Rotator Cuff Repair.

Background: Healing of the rotator cuff after repair constitutes a major clinical challenge with reported high failure rates. Identifying structural musculotendinous predictors for failed rotator cuff repair could enable improved diagnosis and management of patients with rotator cuff disease. Purpose: To investigate structural predictors of the musculotendinous unit for failed tendon healing after rotator cuff repair. Study Design: Cohort study; Level of evidence, 2. Methods: Included were 116 shoulders of 115 consecutive patients with supraspinatus (SSP) tear documented on magnetic resonance imaging (MRI) who were treated with an arthroscopic rotator cuff repair. Preoperative assessment included standardized clinical and imaging (MRI) examinations. Intraoperatively, biopsies of the joint capsule, the SSP tendon, and muscle were harvested for histological assessment. At 3 and 12 months postoperatively, patients were re-examined clinically and with MRI. Structural and clinical predictors of healing were evaluated using logistic and linear regression models. Results: Structural failure of tendon repair, which was significantly associated with poorer clinical outcome, was associated with older age (ß = 1.12; 95% CI, 1.03 to 1.26; P = .03), shorter SSP tendon length (ß = 0.89; 95% CI, 0.8 to 0.98; P = .02), and increased proportion of slow myosin heavy chain (MHC)-I/fast MHC-II hybrid muscle fibers (ß = 1.23; 95% CI, 1.07 to 1.42; P = .004). Primary clinical outcome (12-month postoperative Constant score) was significantly less favorable for shoulders with fatty infiltration of the infraspinatus muscle (ß = -4.71; 95% CI, -9.30 to -0.12; P = .044). Conversely, a high content of fast MHC-II muscle fibers (ß = 0.24; 95% CI, 0.026 to 0.44; P = .028) was associated with better clinical outcome. Conclusion: Both decreased tendon length and increased hybrid muscle fiber type were independent predictors for retear. Clinical outcome was compromised by tendon retearing and increased fatty infiltration of the infraspinatus muscle. A high content of fast MHC-II SSP muscle fibers was associated with a better clinical outcome. Registration: NCT02123784 (ClinicalTrials.govidentifier).

Posterior stability of the shoulder depends on acromial anatomy: a biomechanical study of 3D surface models.

PURPOSE: Primary glenohumeral osteoarthritis is commonly associated with static posterior subluxation of the humeral head. Scapulae with static/dynamic posterior instability feature a superiorly and horizontally oriented acromion. We investigated whether the acromion acts as a restraint to posterior humeral translation. METHODS: Five three-dimensional (3D) printed scapula models were biomechanically tested. A statistical shape mean model (SSMM) of the normal scapula of 40 asymptomatic shoulders was fabricated. Next, a SSMM of scapular anatomy associated with posterior subluxation was generated using data of 20 scapulae ("B1"). This model was then used to generate three models of surgical correction: glenoid version, acromial orientation, and acromial and glenoid orientation. With the joint axially loaded (100N) and the humerus stabilized, an anterior translation force was applied to the scapula in 35°, 60° and 75° of glenohumeral flexion. Translation (mm) was measured. RESULTS: In the normal scapula, the humerus translates significantly less to contact with the acromion compared to all other configurations (p < .000 for all comparisons; i.e. 35°: "normal" 8,1 mm (± 0,0) versus "B1" 11,9 mm (± 0,0) versus "B1 Acromion Correction" 12,2 mm (± 0,2) versus "B1 Glenoid Correction" 13,3 mm (± 0,1)). Restoration of normal translation was only achieved with correction of glenoid and acromial anatomy (i.e. 75°: "normal" 11 mm (± 0,8) versus "B1 Acromion Correction" 17,5 mm (± 0,1) versus "B1 Glenoid Correction" 19,7 mm (± 1,3) versus "B1 Glenoid + Acromion Correction" 11,5 mm (± 1,1)). CONCLUSIONS: Persistence or recurrence of static/dynamic posterior instability after correction of glenoid version alone may be related to incomplete restoration of the intrinsic stability that is conferred by a normal acromial anatomy. LEVEL OF EVIDENCE V: biomechanical study.