Tendons are sparsely vascularized connective tissues that link muscles to bones, withstanding some of the highest mechanical stresses in the body. Mechanical overloading and tissue hypervascularity are implicated in tendinopathy, a common musculoskeletal disorder, yet their mechanistic roles remain unclear. Here, we identify hypoxia-inducible factor 1α (HIF1α) as not only a marker but also a driver of tendinopathy. Histological and multiomics evaluation of human tendinopathic samples revealed extensive extracellular matrix remodeling, including pathological collagen cross-linking coinciding with active hypoxic signaling. Hypothesizing a causal contribution of hypoxia signaling, we generated mice with tenocyte-targeted deletions of the von Hippel–Lindau ( Vhl ) gene, which controls hypoxia signaling by regulating HIFα degradation. Vhl inactivation was sufficient to induce pathological hallmarks of tendinopathy, such as collagen matrix disorganization, cross-linking, altered mechanics, and neurovascular ingrowth. This phenotype was HIF1α dependent given that codeleting HIF1α rescued tendon morphology and mechanics. Moreover, deleting vascular endothelial growth factor A ( Vegfa ) alongside VHL effectively suppressed neovascularization but failed to rescue extracellular matrix abnormalities or restore mechanical function, emphasizing a direct role of HIF1α in driving tendon disease independently of angiogenesis. Mechanistically, we found that HIF1α activation was strain dependent in primary cultured human tendon cells and induced by mechanical overload in murine tendon explants. Furthermore, genetically removing Hif1 α from tenocytes prevented aberrant tendon remodeling in response to chronic overload. These findings position HIF1α signaling as a central driver of tendinopathy that acts through a maladaptive tissue response to chronic overload, providing mechanistic insights that could be leveraged for therapeutic approaches.

Background: The severity of fatty infiltration (FI) predicts the treatment outcome of rotator cuff tears. The purpose of this investigation was to quantitatively analyze supraspinatus (SSP) muscle FI and volume at the initial presentation and after a 3-month minimum of conservative management. We hypothesized that progression of FI could be predicted with initial tear size, FI, and muscle volume. Methods: Seventy-nine shoulders with rotator cuff tears were prospectively enrolled, and 2 magnetic resonance imaging (MRI) scans with 6-point Dixon sequences were acquired. The fat fraction within the SSP muscle was measured on 3 sagittal slices, and the arithmetic mean was calculated (FI^SSP). Advanced FI^SSP was defined as ≥8%, pathological FI^SSP was defined as ≥13.5%, and relevant progression was defined as a ≥4.5% increase in FI^SSP. Furthermore, muscle volume, tear location, size, and Goutallier grade were evaluated. Results: Fifty-seven shoulders (72.2%) had normal FI^SSP, 13 (16.5%) had advanced FI^SSP, and 9 (11.4%) had pathological FI^SSP at the initial MRI scan. Eleven shoulders (13.9%) showed a ≥4.5% increase in FI^SSP at 19.5 ± 14.7 months, and 17 shoulders (21.5%) showed a ≥5-mm³ loss of volume at 17.8 ± 15.3 months. Five tears (7.1%) with initially normal or advanced FI^SSP turned pathological. These tears, compared with tears that were not pathological, had significantly higher initial mediolateral tear size (24.8 compared with 14.3 mm; p = 0.05), less volume (23.5 compared with 34.2 mm³; p = 0.024), more FI^SSP (9.6% compared with 5.6%; p = 0.026), and increased progression of FI^SSP (8.6% compared with 0.5%; p < 0.001). An initial mediolateral tear size of ≥20 mm yielded a relevant FI^SSP progression rate of 81.8% (odds ratio [OR], 19.0; p < 0.001). Progression rates of 72.7% were found for both initial FI^SSP of ≥9.9% (OR, 17.5; p < 0.001) and an initial anteroposterior tear size of ≥17 mm (OR, 8.0; p = 0.003). Combining these parameters in a logistic regression analysis led to an area under the receiver operating characteristic curve (AUC) of 0.913. The correlation between FI^SSP progression and the time between MRI scans was weak positive (ρ = 0.31). Conclusions: Three risk factors for relevant FI progression, quantifiable on the initial MRI, were identified: ≥20-mm mediolateral tear size, ≥9.9% FI^SSP, and ≥17-mm anteroposterior tear size. These thresholds were associated with a higher risk of tear progression: 19 times higher for ≥20-mm mediolateral tear size, 17.5 times higher for ≥9.9% FI^SSP, and 8 times higher for ≥17-mm anteroposterior tear size. The presence of all 3 yielded a 91% chance of ≥4.5% progression of FI^SSP within a mean of 19.5 months. Level of Evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Chordomas are rare, locally aggressive, malignant tumors. Surgical resection with sufficient margins defines the outcome. However, the necessity for wide margins often leads to sacrifice of important neurological structures. 3D-printed osteotomy guides are a promising solution for precise execution of surgical resection. We present probably the first sacrococcygeal chordoma resection with 3D-printed guides. The case of a 49-year-old woman with a sacrococcygeal chordoma, resected with help of 3-D pre-operative planning and patient-specific 3D-printed osteotomy guides, is reported in detail. A sufficient tumor excision could be performed successfully while sparing nerve root S4. The planed margin has been exactly maintained, as confirmed by histology. The patient demonstrated an excellent clinical outcome with no evidence of local recurrence. 3-D pre-operative planning and patient-specific osteotomy guides can be used for planning and performing en-bloc surgical resection of sacral chordomas.

Literature reports varied incidences and clinical relevance of Popeye’s sign in patients who underwent biceps tenotomy or tenodesis. There is no consensus according to indication and outcome. We aimed to evaluate the frequency of the Popeye sign in a large cohort of patients concomitantly treated with an arthroscopic rotator cuff repair (ARCR). We assessed the effect on the clinical outcome based on biceps tendon treatment and Popeye sign. A cohort of 973 primary ARCR patients from different Swiss and German orthopedic clinics was prospectively documented for up to 24 months postoperatively. All patients who received biceps tendon treatment were included in this study. We assessed Popeye sign occurrence across groups treated either with tenodesis or tenotomy. Additionally, we compared clinical and radiological outcome between Popeye/non-Popeye and tenotomy/tenodesis groups. Eight hundred patients were evaluated, of which 55% (n = 442) underwent tenodesis and 45% (n = 358) received tenotomy of the long head of the biceps tendon. Mean age of the tenodesis group was significantly lower than that of the tenotomy group (55 ± 9 and 61 ± 8 years, P < .001). The other demographics were comparable. Among the patients with tenotomy, 20% (n = 63) developed a Popeye sign, compared to only 6.3% (n = 25) in the tenodesis group (age-adjusted relative risk 3, 95% confidence interval 1.9-4.8; P < .001). There were no significant differences in shoulder function. The subjective shoulder value was lower in the Popeye group (82 ± 19% vs. 86 ± 15%, P = .010). Patients with tenotomy of the biceps tendon are 3 times more likely to develop a Popeye sign compared to tenodesis. Popeye sign after ARCR seems to have no relevant effect on the clinical outcome and pain even though the subjective shoulder value was lower in patients with Popeye sign.

Previous studies have found varied outcomes for elderly patients following reverse total shoulder arthroplasty (rTSA). Results for very old patients are rare. The purpose of this study was to analyze functional and radiographic outcomes after rTSA in patients aged 85 years and older and to compare them to a younger population. Of 1460 patients treated with rTSA from 2005 to 2020, 5% (n = 74) were ≥85 years. 32 patients were excluded due to travel difficulties, death, refuse to participate and lost to follow-up. 42 patients with a minimum follow-up of 2 years were included and matched for sex, body mass index, American Society of Anesthesiologists Score, surgical indication, smoking, alcohol consume, and follow-up time to a younger population with a mean age of 69.5 ± 9 years. Statistical analysis was performed based on preoperative and postoperative range of motion (ROM), pain scores and patient satisfaction. Postoperative X-rays were evaluated for notching, radiolucency, bone formation and resorption, implant migration and periprosthetic fractures. 42 cases with a mean age of 87 ± 2 years were included, 71% female. Indications for rTSA were rotator cuff (RC) tear with arthritis (36%), RC arthropathy (17%), RC tear without arthritis (17%), primary arthritis (17%), proximal humeral fracture (10%), failed osteosynthesis (7%), and instability (2%). Mean follow-up was 47 ± 22 months. Except for age, there were no significant differences in the matching cohort. In the elderly cohort, relative Constant-Murley Score (CMS) improved postoperative significantly from 41 ± 20 to 83 ± 11 and subjective shoulder value from 38 ± 20 to 80 ± 19. All aspects of ROM, except for external rotation, improved significantly. Abduction force and pain improved as well. Radiolucency around the glenoid (21%), bone formation (4.9%) and implant migration (4.9%) were significantly associated with poorer outcome in the absolute CMS (P = .013, P = .002 and P = .008). One patient (1/42, 2.4%) suffered multiple shoulder dislocations and needed a revision. No other reoperations were performed. Comparison between patients over 85 years and the younger matched control group showed no significant differences in relative CMS, subjective shoulder value, and ROM at final follow-up. Patients aged 85 years and older can expect significant improvement in shoulder function and significant reduction of pain after rTSA. Overall clinical outcome is comparable to a younger population. Complication and revision rates are low. Age should not be a limiting factor when considering rTSA.

Tendons are mostly avascular dense connective tissues that link muscles to bones, withstanding some of the highest mechanical stresses in the body. Mechanical overload and tissue hypervascularity are implicated in tendinopathy, a common musculoskeletal disorder, but mechanistic understanding of their roles is largely lacking. Here, we identify HIF1α not only as a marker but as a driver of tendinopathy. Initial histological and multi-omics evaluation of human tendinopathic samples revealed extensive extracellular matrix remodeling, including pathological collagen crosslinking coinciding with active hypoxic signaling. Hypothesizing a causal contribution of hypoxia signaling, we generated mice with tenocyte-targeted deletions of the Von Hippel-Lindau (VHL) gene, which controls hypoxia signaling by regulating HIFα degradation. We demonstrated that VHL inactivation suffices to induce pathological hallmarks of tendinopathy, such as collagen matrix disorganization, crosslinking, altered mechanics and neuro-vascular ingrowth. This phenotype was HIF1α-dependent, since co-deleting HIF1α rescued tendon morphology and mechanics. Moreover, deleting vascular endothelial growth factor A (VEGFA) alongside VHL effectively decoupled the effects of vascular ingrowth from persistently aberrant extracellular matrix remodeling and mechanical dysfunction, emphasizing a direct role of HIF1α in driving tendon disease that is independent of angiogenesis. Mechanistically, we linked tendon mechanical overload to the onset of HIF1α signaling in primary cultured human tendon cells. Furthermore, genetically removing HIF1α from tenocytes prevented aberrant tendon remodeling in response to chronic overload. These findings position HIF1α signaling as a central driver of tendinopathy that acts through a maladaptive tissue response to chronic overload, providing mechanistic insights that could be leveraged for improved therapeutic approaches. One Sentence Summary HIF1α activation promotes tendinopathy and its inhibition prevents overload-induced maladaptation, suggesting therapeutic potential.