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.

Mid- to long-term clinical and radiological results of anatomic total shoulder arthroplasty in patients with B2 glenoids.

Background: Eccentric biconcave (B2) glenoid erosion in primary glenohumeral arthritis is common. There are serious concerns regarding the longevity of fixation of cemented glenoids if anatomic total shoulder arthroplasties (aTSAs) are used in B2 glenoid. The purpose of this study is to analyze the mid- to long-term results of aTSA with B2 glenoids. Methods: This is a retrospective study of a single center experience. Thirty patients (32 shoulders) at an average of 9.2 years (range, 5.0-16.6, ±3.2) after primary TSA were evaluated. Clinical and radiographic outcomes were analyzed. Results: The mean preoperative intermediate glenoid version was -14° ± 7° (range, -2° to -29°) and the mean humeral subluxation according to the plane of the scapula was 67% ± 9% (range, 49%-87%). There was a significant improvement for all the postoperative clinical outcome parameters including the mean absolute and relative Constant Score, subjective shoulder value, active elevation, external rotation, abduction, internal rotation, pain scores, and strength (P < .001). The complication rate was 15.6% and the revision rate was 12.5% at a mean follow-up of 9.2 years (range, 5.0-16.6, ±3.2). The estimated survivorship without revision was 94% at 5 years and 85% at 10 years (12.1-14.7 years). The survival rate without advanced glenoid component loosening (defined as Lazarus grade ≥ 4 or modified Molé scores ≥ 6) was 91% at 5 years and 84% at 10 years (12.2-15.8 years). Conclusion: In this case series, aTSA with asymmetric reaming for the treatment of shoulder osteoarthritis with milder forms of B2 glenoid is a viable option with good to excellent clinical results and an 85% prosthetic survivorship at 10 years.

Correction of Static Posterior Shoulder Subluxation by Restoring Normal Scapular Anatomy Using Acromion and Glenoid Osteotomies: A Case Report.

CASE: A 40-year-old man presented with progressive shoulder pain, associated with static posterior subluxation and mild eccentric glenohumeral osteoarthritis. Compared with a mean statistical shape model of a normal shoulder, the patient's acromion was abnormally high and horizontal, and the glenoid abnormally inclined inferiorly and minimally retroverted. Restoration of normal scapular anatomy using 3-dimensional planned acromial and glenoid osteotomies led to recentering of the joint and full shoulder function up to 24 months postoperatively. CONCLUSION: The correction of associated acromial and glenoid malformation can revert early static posterior subluxation of the shoulder. Whether successful recentering prevents progression of osteoarthritis remains to be established.

Mid-term to long-term results of open posterior bone block grafting in recurrent posterior shoulder instability: a clinical and CT-based analysis.

Background: There is little consensus on the best treatment after failed conservative management of recurrent posterior shoulder instability. The purpose of this study was to analyze our clinical and radiological mid-term to long-term results of an open, posterior bone block procedure for the treatment of recurrent posterior shoulder instability. Methods: From 1999 to 2015, 14 patients were included in the study and available for clinical and radiographic follow-up (FU). FU included a standardized physical examination, assessment of the Constant-Murley-Score, subjective shoulder value, American Shoulder and Elbow Surgeons score, and Western Ontario Shoulder Instability Index. Conventional radiographs and a computed tomography (CT)-scan were performed preoperatively and at latest FU. Glenohumeral arthropathy was classified as per Samilson and Prieto. The CT scans were used to evaluate the structure of the graft (resorption, union), graft positioning, glenoid version, centering of the humeral head, and glenoid erosion and morphology. Results: The median age at the time of surgery was 26 years (range 16-41 years) and the median FU period was 9 years (range 4-20 years). The rate of reported dynamic postoperative subluxation and instability was 46% (n = 6) and the rate of dynamic posterior instability during clinical testing at FU was 31% (n = 4). The tested instability rate in the traumatic group was 14% (n = 1) compared to the atraumatic group with 50% (n = 3) during clinical FU. The mean Constant-Murley-Score increased from preoperatively (77 ± 11 points) to postoperatively (83 ± 14 points, P = .158). The last FU showed an American Shoulder and Elbow Surgeons score of 85 ± 12; the Western Ontario Shoulder Instability Index score was 715 ± 475 points. The mean subjective shoulder value increased from 58% ± 19 preoperatively to 73% ± 17 at final FU (P = .005). Degenerative changes increased by at least one grade in 67% of the patients. Mean preoperative glenoid retroversion (CT) was 7.5° ± 6°. The position of the graft was optimal in 86% (n = 12). In 62% of the cases, a major resorption of the graft (Zhu grade II) was observed. Conclusion: The rate of tested recurrent instability at last FU was as high as 31% (n = 4, atraumatic [n = 3] vs. traumatic [n = 1]) after a median FU of 9 years. Given the moderate improvement of clinical outcome scores, shoulder stability and the increase of degenerative joint changes by at least one grade (Samilson/Prieto) in 67% of patients, a posterior bone block procedure is not a uniformly satisfying treatment option for recurrent posterior shoulder subluxation, especially in cases of atraumatic posterior instability.

Computer-assisted analysis of functional internal rotation after reverse total shoulder arthroplasty: implications for component choice and orientation.

PURPOSE: Functional internal rotation (IR) is a combination of extension and IR. It is clinically often limited after reverse total shoulder arthroplasty (RTSA) either due to loss of extension or IR in extension. It was the purpose of this study to determine the ideal in-vitro combination of glenoid and humeral components to achieve impingement-free functional IR. METHODS: RTSA components were virtually implanted into a normal scapula (previously established with a statistical shape model) and into a corresponding humerus using a computer planning program (CASPA). Baseline glenoid configuration consisted of a 28 mm baseplate placed flush with the posteroinferior glenoid rim, a baseplate inclination angle of 96° (relative to the supraspinatus fossa) and a 36 mm standard glenosphere. Baseline humeral configuration consisted of a 12 mm humeral stem, a metaphysis with a neck shaft angle (NSA) of 155° (+ 6 mm medial offset), anatomic torsion of -20° and a symmetric PE inlay (36mmx0mm). Additional configurations with different humeral torsion (-20°, + 10°), NSA (135°, 145°, 155°), baseplate position, diameter, lateralization and inclination were tested. Glenohumeral extension of 5, 10, 20, and 40° was performed first, followed by IR of 20, 40, and 60° with the arm in extension of 40°-the value previously identified as necessary for satisfactory clinical functional IR. The different component combinations were taken through simulated ROM and the impingement volume (mm3) was recorded. Furthermore, the occurrence of impingement was read out in 5° motion increments. RESULTS: In all cases where impingement occurred, it occurred between the PE inlay and the posterior glenoid rim. Only in 11 of 36 combinations full functional IR was possible without impingement. Anterosuperior baseplate positioning showed the highest impingement volume with every combination of NSA and torsion. A posteroinferiorly positioned 26 mm baseplate resulting in an additional 2 mm of inferior overhang as well as 6 mm baseplate lateralization offered the best impingement-free functional IR (5/6 combinations without impingement). Low impingement potential resulted from a combination of NSA 135° and + 10° torsion (4/6 combinations without impingement), followed by NSA 135° and -20° torsion (3/6 combinations without impingement) regardless of glenoid setup. CONCLUSION: The largest impingement-free functional IRs resulted from combining a posteroinferior baseplate position, a greater inferior glenosphere overhang, 90° of baseplate inclination angle, 6 mm glenosphere lateralization with respect to baseline setup, a lower NSA and antetorsion of the humeral component. Surgeons can employ and combine these implant configurations to achieve and improve functional IR when planning and performing RTSA. LEVEL OF EVIDENCE: Basic Science Study, Biomechanics.

Effect of Abduction Brace Wearing Compliance on the Results of Arthroscopic Rotator Cuff Repair.

The benefit of protective bracing after rotator cuff reconstruction has been debated for many years, although immobilization compliance has never been assessed objectively to date. In a previous study, compliance with the wearing of an abduction brace was measured for the first time with use of temperature-sensitive sensors. The purpose of the present follow-up study was to assess the effect of immobilization compliance on tendon-healing after rotator cuff repair. Methods: The clinical and radiographic outcomes for 46 consecutive patients with objectively assessed abduction brace wearing compliance after arthroscopic repair of a superior rotator cuff tear were prospectively analyzed. Rotator cuff integrity was examined with ultrasound. Clinical outcomes were assessed with the relative Constant-Murley score (RCS), the Subjective Shoulder Value (SSV), and pain and patient satisfaction ratings. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff value of abduction brace compliance for discriminating between shoulders that will and will not have a retear and the association of compliance with the failure of rotator cuff repair. Results: After a mean duration of follow-up of 20 ± 9 months, the odds ratio for having a rotator cuff repair failure was 13-fold higher for patients with a compliance rate of <60% (p = 0.037). The retear rate was 3% (1 of 35 patients) in the high-compliance cohort (≥60% compliance) and 27% (3 of 11) in the low-compliance cohort (<60% compliance) (p = 0.037). No differences in RCS, SSV, pain, or postoperative patient satisfaction were observed between patients with ≥60% compliance and those with <60% compliance. Conclusions: Patients with a compliance rate of <60% had a 13-fold increase in the risk of rotator cuff retear. The 2 patients with the lowest compliance rates (11% and 22%) both had retears. Due to the small sample size, no final conclusions can be drawn regarding the influence of immobilization compliance on tendon-healing after rotator cuff repair. These findings justify a prospective trial with a larger cohort to confirm or disprove the value of compliance with abduction bracing. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Clinical results of conservative versus operative treatment of acromial and scapular spine fractures following reverse total shoulder arthroplasty.

BACKGROUND: Acromial and scapular spine fractures are common complications after reverse total shoulder arthroplasty (RTSA). There is limited information on the treatment outcome of these fractures. Therefore, the purpose of this study was to compare the clinical outcome of operative and conservative treatment of patients with acromial or scapular spine fractures. METHODS: A total of 1146 RTSAs were performed in our institution between 1999 and 2016. In 23 patients (2%), we identified an acromial fracture, and in 7 cases (0.6%), a scapular spine fracture in the postoperative course. Of those patients, 7 patients (23%) were treated with open reduction and internal fixation and 23 (77%) were treated conservatively. We compared the outcome of operative vs. conservative treatment assessing the Constant score (CS), range of motion, and subjective shoulder value (SSV). Fractures were classified by the system of Crosby. Radiographic assessment consisted of measuring the healing rate, time to heal, and the displacement of the acromion before and immediately after the fracture as well as after treatment. RESULTS: There were no statistically significant differences between operative and conservative treatment. The mean preoperative CS in the operative group was 32 points and improved to 45 points after surgery, whereas it was 35 points in the conservative group and improved to 61 points at the final follow-up. The mean SSV improved from 20 to 50 points in the operative group and from 22 to 58 points in the conservative group. Mean active flexion changed from 59° to 75°, mean abduction from 68° to 67°, and external rotation from 25° to 13° in the operative group and from 75° to 91°, 67° to 92°, and 28° to 24° in the conservative group. CONCLUSIONS: In our study, operative treatment was not superior to conservative treatment, neither for CS, SSV, or range of motion. Both treatment forms, however, resulted in inferior results to those previously reported for RTSA without postoperative acromion fractures. Before better surgical methods have been developed, conservative treatment of acromial fractures may be the better treatment option for acromial fractures after RTSA.

Nonoperatively managed small- to medium-sized subscapularis tendon tears: magnetic resonance imaging evaluation with a minimum of 5 years of follow-up.

BACKGROUND: Isolated or combined subscapularis (SSC) tendon tears are frequently found in patients with shoulder pain. The purpose of this study was to evaluate the structural changes associated with SSC tear in a consecutive series of patients with nonoperatively treated small size to midsize SSC tendon tears using magnetic resonance imaging (MRI). METHODS: In this retrospective case series, all patients with an isolated or combined SSC tendon tear treated nonoperatively between 1999 and 2019 were identified from our MRI and clinical databases. Twenty-one patients with a mean age of 52.6 years (range 26.6-64.8, standard deviation 9.3) with a second MRI scan at a minimum of 5 years of follow-up were enrolled. The mean follow-up was 8.6 years (range 5.6-12.6, standard deviation 1.8). Initial and last follow-up MRI scans were used to determine concomitant cuff lesions, size of the SSC tear, fatty infiltration of the SSC muscle, and biceps pathology. RESULTS: Five patients had an isolated SSC lesion; 7 patients had a concomitant tear of the supraspinatus, and 9 patients had a supraspinatus and anterior infraspinatus tendon tear. At diagnosis, 14 patients had a type 1 SSC lesion as classified by Lafosse et al, 4 patients had type 2, and 3 patients had type 3 lesions. Nineteen patients (90%) were found to have an SSC tear progression of at least one Lafosse grade (P < .001); however, no tear had progressed to an irreparable type lesion (defined as Lafosse type 5). In addition, the size of SSC tendon tears increased significantly from 75 mm2 to 228 mm2 (P < .001). At the final MRI scan, the grading of fatty infiltration increased by 1 grade in 4 cases and by 2 grades in 4 cases (P = .042). At the final follow-up, in eight patients, the condition of the long head of biceps tendon was unchanged from the initial MRI; in nine patients, there was a newly subluxated biceps tendon, and in 6 patients, there was a newly ruptured long head of biceps tendon (P < .001). CONCLUSION: After a mean of 8.6 years, almost all nonoperatively treated SSC tendon tears had increased in size, but only one-third showed additional progression of muscle fatty degeneration on MRI scan. None of the SSC lesions became irreparable during the observation period.

Extension of the shoulder is essential for functional internal rotation after reverse total shoulder arthroplasty.

BACKGROUND: Disabling loss of functional internal rotation (fIR) after reverse total shoulder arthroplasty (RTSA) is frequent but not well understood. This study tested the hypothesis that limitation of fIR after RTSA is not primarily related to a deficit in internal rotation. METHODS: Fifty patients (mean age at RTSA, 74 ± 11.7 years) who were consecutively seen at a yearly follow-up visit at 1-10 years (median, 4 years) after RTSA were prospectively examined with special attention to fIR. Patients with axillary nerve or deltoid dysfunction were excluded. Relative (age- and sex-adjusted) Constant-Murley scores (CSs) and Subjective Shoulder Values were assessed preoperatively and at final follow-up. In addition, active extension and 4 postoperative activities of daily living (ADLs) requiring fIR were tested at follow-up. Rotator cuff fatty infiltration and notching were evaluated radiographically. For analysis, patients were divided into a group with poor fIR (fIR-, n = 19), defined as ≤2 internal-rotation points in the CS, and a group with good fIR (fIR+, n = 31), defined as ≥4 internal-rotation points in the CS. RESULTS: Active extension of the contralateral shoulders was comparable in the fIR- group (mean, 60.3° [standard deviation (SD), 11.2°]) and fIR+ group (66.1° [SD, 14.2°]). Postoperatively, a difference in active extension between the unaffected and operated sides was present in both groups and averaged 16° (55° [SD, 14.3°] in fIR+ group and 39.1° [SD, 10.8°] in fIR- group; P < .001). No patient in the fIR+ group had active extension < 40° (range, 40°-85°). Shoulders with extension ≥ 40° but unsatisfactory fIR had restricted passive internal rotation in extension. The ability to perform ADLs behind the back correlated better with shoulder extension than with so-called fIR measurements in the CS. CONCLUSION: Functional internal rotation after RTSA requires at least 40° of shoulder extension. If fIR is unsatisfactory despite 40° of extension, passive restriction of internal rotation in full extension is the limiting factor. It is crucial to preserve or restore active shoulder extension to allow ADLs involving internal rotation.

Targeting Ion Channel TRPM4.

The transient receptor potential melastatin 4 (TRPM4) ion channel is ubiquitously expressed. Dysregulation and/or functional mutations of TRPM4 lead to several diseases. Within our studies, we screened for TRPM4 inhibitors and identified small molecules that block TRPM4 in the low µM range. Furthermore, we investigated the pathophysiology of TRPM4 in cardiac conditions, immune diseases and cancer using these novel inhibitors, molecular biology techniques and functional assays.

Reverse total shoulder arthroplasty in patients with type B2, B3, and type C glenoids: comparable clinical outcome to patients without compromised glenoid bone stock-a matched pair analysis.

BACKGROUND: Primarily posterior bone deficient (dysplastic) (Walch type C) or secondarily eroded (Walch type B2 or B3) glenoids represent a surgical challenge for shoulder arthroplasty. Due to the posteriorly static decentered head, reverse total shoulder arthroplasty (RTSA) is often considered as the treatment of choice. The purpose of this study is to report the clinical and radiographic outcomes, complications and reoperations of RTSA for posteriorly deficient glenoids. MATERIALS AND METHODS: All patients who underwent RTSA for osteoarthritis secondary to underlying glenoid deficiency (Walch type B2, B3 and C) between 2005 and 2018 (study group), were identified from our institutional shoulder arthroplasty database and gender- and age-matched to a cohort of patients with normal glenoid bone stock (control group). Longitudinal pre- and postoperative clinical [Constant-Murley (CS) score, Subjective Shoulder Value (SSV)] and radiographic outcomes were assessed. RESULTS: We included 188 patients (94 in each group). The median follow-up was 43 ± 26 (24-144) months in the study group and 59 ± 32 (24-124) months in the control group. The glenoid deficiency was addressed by using glenoid bone reconstruction. The surgical site complication and revision rate of RTSA in patients with bony deficient glenoids were 17% and 7%. Although glenoid loosening was slightly higher in the study group (5 vs. 2), overall no significant differences were found between the study and control groups in satisfaction scores, preoperative and postoperative absolute and relative Constant scores, complication and revision rates, respectively. CONCLUSION: Reverse total shoulder arthroplasty (RTSA) seems to be a valuable treatment option for patients with primary (dysplasia) or secondary (wear) posterior glenoid deficiency. Although severe glenoid bone loss seems to be a risk factor for glenoid component failure, the overall complication and revision rates as well as clinical and radiographic outcome are comparable to RTSA in patients without compromised glenoid bone stock. LEVEL OF EVIDENCE: Level III: case-control study.

Long-term results after posterior open glenoid wedge osteotomy for posterior shoulder instability associated with excessive glenoid retroversion.

BACKGROUND: Treatment of posterior shoulder instability (PSI) associated with excessive glenoid retroversion is a rare, challenging problem in shoulder surgery. One proposed technique is posterior open wedge glenoid osteotomy to correct excessive glenoid retroversion as described by Scott. However, this operation is rarely performed, and limited long-term outcomes using this approach are available. The goal of this study was to analyze the long-term outcomes of posterior open wedge glenoid osteotomy for PSI associated with excessive glenoid retroversion. METHODS: Six consecutive patients (7 shoulders) with a mean age of 24 years (range 19-34) were treated with posterior open wedge glenoid osteotomy for PSI associated with a glenoid retroversion greater than 15° and followed up clinically and radiographically at a mean age of 15 years (range 10-19). RESULTS: Recurrent, symptomatic PSI was observed in 6 of 7 shoulders (86%). One necessitated revision with a posterior (iliac crest) bone block procedure and was rated as a failure and excluded from functional analysis. One patient rated his result as excellent, 3 as good, 1 as fair, and 1 as unsatisfactory. Mean relative Constant Score (CS%) was unchanged from preoperation to final follow-up (CS% = 72%) and pain did not significantly decrease (Constant Score = 7-10 points; P = .969). The mean Subjective Shoulder Value (SSV) improved postoperatively, but with 6 patients the improvement did not reach statistical significance (SSV = 42%-67%, P = .053) and the total Western Ontario Shoulder Instability Index averaged 30% at the final follow-up. Mean glenoid retroversion of all 7 shoulders was corrected from 20° (range 16°-26°) to 3° (range -3° to +8°) (P = .018). In the 5 shoulders with preoperative static posterior subluxation of the humeral head, the humeral head was not recentered. All 7 shoulders showed progression of glenoid arthritic changes. CONCLUSIONS: Posterior open wedge glenoid osteotomy for PSI associated with excessive glenoid retroversion neither reliably restored shoulder stability nor recentered the joint or prevent progression of osteoarthritis. Alternative treatments for PSI associated with excessive glenoid retroversion have to be developed and evaluated.

Unacceptable failure of osteochondral glenoid allograft for biologic resurfacing of the glenoid.

PURPOSE: Glenohumeral osteoarthritis (OA) represents a challenging problem in young, physically active patients. It was the purpose of this investigation to evaluate the results of a pilot study involving glenoid resurfacing with a glenoid allograft combined with a hemiarthroplasty on the humeral side. METHODS: Between April 2011 to November 2013, 5 patients (3 men, 2 women, mean age 46.4, range 35-57) with advanced OA of the glenohumeral joint, were treated with a humeral head replacement combined with replacement of the glenoid surface with an osteochondral, glenoid allograft. RESULTS: Overall, clinically, there was one excellent, one satisfactory and three poor results. Mean preoperative subjective shoulder value (SSV) was 34% (range: 20-50%) and preoperative relative Constant-Murley-Score (CSr) was 43 points (range: 29-64 points). Three patients with poor results had to be revised within the first three years. Their mean pre-revision SSV and CSr were 38% (range: 15-80%) and 36 points (range: 7-59 points) respectively. One patient was revised 9 years after the primary procedure with advanced glenoid erosion and pain and one patient has an ongoing satisfactory outcome without revision. Their SSVs were 60% and 83%, their CSr were 65 points and 91 points, 9 and 10 years after the primary procedure, respectively. Mean follow-up was 7 years (2-10 years) and mean time to revision was 4 years (range: 1-9 years). CONCLUSION: The in-vivo pilot study of a previously established in-vitro technique of osteochondral glenoid allograft combined with humeral HA led to three early failures and only one really satisfactory clinical outcome which, however, was associated with advanced glenoid erosion. Osteochondral allograft glenoid resurfacing was associated with an unacceptable early failure rate and no results superior to those widely documented for HA or TSA, so that the procedure has been abandoned. LEVEL OF EVIDENCE: Level IV, Case Series, Treatment Study.