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Background: The long head of the biceps tendon (LHBT) is a well-known source of pain in the shoulder, especially in active patients., Purpose: To evaluate the outcomes and return-to-sports rate after all-arthroscopic suprapectoral tenodesis of the LHBT using a small knotless anchor., Study Design: Case series; Level of evidence, 4., Methods: In this retrospective study, 27 patients-who underwent all-arthroscopic tenodesis of the LHBT using a 2.7-mm knotless polyether ether ketone anchor-were evaluated. Sports activities, the return-to-sports rate, and other sports-related parameters (eg, pain during sports, level of sports) were examined. Sports-related data, the Constant score with isometric force (at 90° of abduction in the scapular plane), the American Shoulder and Elbow Surgeons (ASES) score, the Simple Shoulder Test (SST) score, the visual analog scale (VAS) score for satisfaction, range of motion, and the presence of a Popeye deformity were assessed at a mean follow-up of 15.3 ± 8.7 months. The data were initially analyzed using descriptive statistics., Results: The postoperative ASES, Constant, and SST scores were 81.61, 85.74 and 8.85, respectively. Of the 27 patients, 4 patients (14.8%) showed a Popeye deformity. Preoperatively, 25 patients (92.6%) participated regularly in some type of sports activity. All 25 patients (100.0%) were able to return to sports activities after surgery. 24 (96.0%) returned to the same level preoperatively, with 88.0% (22/25) within 6 months. Patient satisfaction with the outcome was high (VAS score: 2.15 ± 2.78). Neither bicipital groove pain nor cramping was reported. There were no signs of osteolytic bone around the anchor or a fracture of the humeral bone., Conclusion: Our clinical results after using a 2.7-mm knotless anchor for LHBT tenodesis as well as the return-to-sports rate were satisfying. Using an anchor this size can lower the risk of cortical bone damage and therefore the risk of fractures of the humeral head while still enabling patients to perform at a high level., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: The Department of Orthopedic and Trauma Surgery at Klinik Diakonissen Schladming has received honoraria from Smith+Nephew. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

Background : Reversed total shoulder arthroplasty (RTSA) is an established surgery for many pathologies of the shoulder and the demand continues to rise with an aging population. Preoperative planning is mandatory to support the surgeon's understanding of the patient's individual anatomy and, therefore, is crucial for the patient's outcome. Methods : In this observational study, we identified 30 patients who underwent RTSA with two- and three-dimensional preoperative planning. Each patient underwent new two-dimensional planning from a medical student and an orthopedic resident as well as through a mid-volume and high-volume shoulder surgeon, which was repeated after a minimum of 4 weeks. The intra- and interobserver reliability was then analyzed and compared to the 3D planning and the implanted prosthesis. The evaluated parameters were the size of the pegged glenoid baseplate, glenosphere, and humeral short stem. Results : The inter-rater reliability showed higher deviations in all four raters compared to the 3D planning of the base plate, glenosphere, and shaft. The intra-rater reliability showed a better correlation in more experienced raters, especially in the planning of the shaft. Conclusions : Our study shows that 3D planning is more accurate than traditional planning on plain X-rays, despite experienced shoulder surgeons showing better results in 2D planning than inexperienced ones.

Downhill-mountain biking (DMB) is a high-risk sport and often leads to several injuries, especially in non-professional athletes. We retrospectively analyzed the most common injuries and profiled the injury mechanism. Until now, there is no such analysis of injuries by non-professional mountain bike athletes. We collected patient data from patients who suffered from an injury during DMB. The inclusion criteria were (1) injury during the summer season of 2020 and 2021, (2) injury during off-road and downhill mountain bike sports activity, and (3) treatment at the Department of Traumatology of the Klinik Diakonissen Schladming. Patient data was analyzed regarding the type of injury, location of the injury, patient age and gender of the patients. Most patients with injury are at the age of 26-35. Second most are between 36 and 71 years old. The type of injury differs between age and gender. Mostly upper-extremity injuries occur with a high probability of shoulder injuries. In the elderly patients, we found additional injuries of the thorax and chest. To conclude, most common types of injuries are soft-tissue injuries, often in combination with fractures. The risk for injuries is higher for recreational athletes with different injury characteristics than professional athletes., (© 2024. The Author(s).)

Proximal hamstring tears are among the most common injuries afflicting athletes and middle-aged individuals. Sciatic nerve compression after a proximal hamstring injury, which can occur due to scar formation and subsequent irritation or compression of the nerve, is an infrequent but severe complication with few cases documented in the literature. No evidence is available about the optimal treatment for sciatic nerve symptoms after proximal hamstring injuries. In this case report, we present two cases involving patients primarily treated conservatively at another institution after suffering from a proximal hamstring injury and developing sciatic nerve symptoms over the course of a few months. Both were treated with open neurolysis at our institution without reattachment of the ruptured muscles to the ischial tuberosity due to the chronicity of the injuries. Both patients exhibited neurological symptoms over two years, which recovered after surgery. These two cases show that neurolysis of the sciatic nerve without reattachment of the proximal hamstring muscles is an applicable option for the treatment of chronic proximal hamstring tears with sciatic nerve compression. Further studies will be needed to validate this hypothesis.

Background and Objectives : Short-stem total hip arthroplasty has become increasingly popular in recent years. While many studies have shown excellent clinical and radiological results, very little is known about the learning curve for short-stem total hip arthroplasty through an anterolateral approach. Therefore, the aim of this study was to determine the learning curve for short-stem total hip arthroplasty among five residents in training. Materials and Methods : We performed retrospective data analysis of the first 30 cases of five randomly selected residents ( n = 150 cases) with no experience before the index surgery. All patients were comparable, and several surgical parameters and radiological outcomes were analyzed. Results : The only surgical parameter with a significant improvement was the surgical time ( p = 0.025). The changes in other surgical parameters and radiological outcomes showed no significant changes; only trends can be derived. As a result, the correlation between surgical time, blood loss, length of stay, and incision/suture time can also be seen. Only two of the five residents showed significant improvements in all examined surgical parameters. Conclusions : There are individual differences among the first 30 cases of the five residents. Some improved their surgical skills faster than others. It could be assumed that they assimilated their surgical skills after more surgeries. A further study with more than 30 cases of the five surgeons could provide more information on that assumption., Competing Interests: The authors declare no conflicts of interest.

Blockade of the CD28:CD80/86 costimulatory pathway has been shown to be potent in blocking T cell activation in vitro and in vivo . The costimulation blocker CTLA4Ig has been approved for the treatment of autoimmune diseases and transplant rejection. The therapeutic application of regulatory T cells (Tregs) has recently gained much attention for its potential of improving allograft survival. However, neither costimulation blockade with CTLA4Ig nor Treg therapy induces robust tolerance on its own. Combining CTLA4Ig with Treg therapy would be an attractive approach for minimizing immunosuppression or for possibly achieving tolerance. However, since the CD28 pathway is more complex than initially thought, the question arose whether blocking CD80/86 would inadvertently impact immunological tolerance by interfering with Treg generation and function. We therefore wanted to investigate the compatibility of CTLA4Ig with regulatory T cells by evaluating direct effects of CTLA4Ig on murine Treg generation and function in vitro . For generation of polyclonal-induced Tregs, we utilized an APC-free in vitro system and added titrated doses of CTLA4Ig at different time points. Phenotypical characterization by flow cytometry and functional characterization in suppressor assays did not reveal negative effects by CTLA4Ig. The costimulation blocker CTLA4Ig does not impair but rather improves murine iTreg generation and suppressor function in vitro .

Background: Therapeutic strategies for the prophylaxis of IgE-mediated allergy remain an unmet medical need. Cell therapy is an emerging approach with high potential for preventing and treating immunological diseases. We aimed to develop a cell-based therapy inducing permanent allergen-specific immunological tolerance for preventing IgE-mediated allergy., Methods: Wild-type mice were treated with allergen-expressing bone marrow cells under a short course of tolerogenic immunosuppression (mTOR inhibition and costimulation blockade). Bone marrow was retrieved from a novel transgenic mouse ubiquitously expressing the major grass pollen allergen Phl p 5 as a membrane-anchored protein (BALB/c-Tg[Phlp5-GFP], here mPhl p 5). After transplantation recipients were IgE-sensitized at multiple time points with Phl p 5 and control allergen., Results: Mice treated with mPhl p 5 bone marrow did not develop Phl p 5-specific IgE (or other isotypes) despite repeated administration of the allergen, while mounting and maintaining a strong humoral response towards the control allergen. Notably, Phl p 5-specific T cell responses and allergic airway inflammation were also completely prevented. Interestingly allergen-specific B cell tolerance was maintained independent of Treg functions indicating deletional tolerance as underlying mechanism., Conclusion: This proof-of-concept study demonstrates that allergen-specific immunological tolerance preventing occurrence of allergy can be established through a cell-based therapy employing allergen-expressing leukocytes., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

The transplantation of allergens (e.g. Phl p 5 or Bet v 1) expressed on BM cells as membrane-anchored full-length proteins leads to permanent tolerance at the T-cell, B-cell, and effector-cell levels. Since the exposure of complete allergens bears the risk of inducing anaphylaxis, we investigated here whether expression of Phl p 5 in the cytoplasm (rather than on the cell surface) is sufficient for tolerance induction. Transplantation of BALB/c BM retrovirally transduced to express Phl p 5 in the cytoplasm led to stable and durable molecular chimerism in syngeneic recipients (∼20% chimerism at 6 months). Chimeras showed allergen-specific T-cell hyporesponsiveness. Further, Phl p 5-specific TH 1-dependent humoral responses were tolerized in several chimeras. Surprisingly, Phl p 5-specific IgE and IgG1 levels were significantly reduced but still detectable in sera of chimeric mice, indicating incomplete B-cell tolerance. No Phl p 5-specific sIgM developed in cytoplasmic chimeras, which is in marked contrast to mice transplanted with BM expressing membrane-anchored Phl p 5. Thus, the expression site of the allergen substantially influences the degree and quality of tolerance achieved with molecular chimerism in IgE-mediated allergy., (© 2013 The Authors. European Journal of Immunology published by Wiley-VCH Verlag GmbH & Co. KGaA Weinheim.)

Molecular chimerism is a promising strategy to induce tolerance to disease-causing antigens expressed on genetically modified haematopoietic stem cells. The approach was employed successfully in models of autoimmunity and organ transplantation. Recently, we demonstrated that molecular chimerism induces robust and lasting tolerance towards the major grass pollen allergen Phl p 5. Since allergens are a group of antigens differing widely in their function, origin and structure we further examined the effectiveness of molecular chimerism using the Phl p 5-unrelated major birch pollen allergen Bet v 1, co-expressed with the reporter GFP. Besides, inhibition of CD26 was used to promote engraftment of modified stem cells. Retrovirus VSV-Betv1-GFP was generated to transduce 5-FU-mobilized BALB/c hematopoietic cells to express membrane-bound Bet v 1 (VSV-GFP virus was used as control). Myeloablated BALB/c mice received Betv1-GFP or GFP expressing bone marrow cells, pre-treated with a CD26 inhibitor. Chimerism was followed by flow cytometry. Tolerance was assessed by measuring allergen-specific isotype levels in sera, RBL assays and T-cell proliferation assays. Mice transplanted with transduced BMC developed multi-lineage molecular chimerism which remained stable long-term (>8 months). After repeated immunizations with Bet v 1 and Phl p 5 serum levels of Bet v 1-specific antibodies (IgE, IgG1, IgG2a, IgG3 and IgA) remained undetectable in Betv1-GFP chimeras while high levels of Phl p 5-specific antibodies developed. Likewise, basophil degranulation was induced in response to Phl p 5 but not to Bet v 1 and specific non-responsiveness to Bet v 1 was observed in proliferation assays. These data demonstrate successful tolerization towards Bet v 1 by molecular chimerism. Stable long-term chimerism was achieved under inhibition of CD26. These results provide evidence for the broad applicability of molecular chimerism as tolerance strategy in allergy., (Copyright © 2013 Elsevier GmbH. All rights reserved.)

While costimulation blockade-based mixed chimerism protocols work well for inducing tolerance in rodents, translation to preclinical large animal/nonhuman primate models has been less successful. One recognized cause for these difficulties is the high frequency of alloreactive memory T cells (Tmem) found in the (pre)clinical setting as opposed to laboratory mice. In the present study, we therefore developed a murine bone marrow transplantation (BMT) model employing recipients harboring polyclonal donor-reactive Tmem without concomitant humoral sensitization. This model was then used to identify strategies to overcome this additional immune barrier. We found that B6 recipients that were enriched with 3 × 10(7) T cells isolated from B6 mice that had been previously grafted with Balb/c skin, rejected Balb/c BM despite costimulation blockade with anti-CD40L and CTLA4Ig (while recipients not enriched developed chimerism). Adjunctive short-term treatment of sensitized BMT recipients with rapamycin or anti-LFA-1 mAb was demonstrated to be effective in controlling Tmem in this model, leading to long-term mixed chimerism and donor-specific tolerance. Thus, rapamycin and anti-LFA-1 mAb are effective in overcoming the potent barrier that donor-reactive Tmem pose to the induction of mixed chimerism and tolerance despite costimulation blockade., (© 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.)

Background: Mixed chimerism is an effective strategy for the induction of transplantation tolerance but the toxicity of recipient conditioning makes current bone marrow (BM) transplantation (BMT) protocols unsuitable for widespread clinical application. Therapies promoting BM engraftment under minimal conditioning would facilitate translation of this concept to the clinic. Recently, we have shown that regulatory T cell (Treg) therapy has potent engraftment-enhancing effects in an irradiation-free noncytotoxic BMT protocol, but only if it is combined with rapamycin treatment., Methods: Here, we investigated whether polyclonal Treg therapy is effective in promoting chimerism and tolerance in an otherwise unsuccessful BMT protocol using low-dose total body irradiation (1 Gy) and costimulation blockade and determined whether Tregs do so on their own without rapamycin., Results: The application of polyclonal FoxP3-transduced recipient Tregs led to durable multilineage chimerism and donor-specific skin graft tolerance whereas recipients receiving costimulation blockade alone or green flourescent protein (GFP)-transduced cells failed to develop chimerism. Infused Tregs had a limited life span as indicated by polymerase chain reaction analysis but rather contribute to de novo induction of subsequent Treg generations. Deletion of donor-reactive T cells was observed but progressed more slowly over time compared with recipients of a nonmyeloablative BMT protocol using 3 Gy total body irradiation., Conclusions: In conclusion, Treg therapy promotes BM engraftment on its own in a low-dose irradiation BMT protocol, leading to chimerism and tolerance maintained through deletional and nondeletional mechanisms.

IgE-mediated allergy is an immunological disorder occurring in response to otherwise harmless environmental antigens (i.e., allergens). Development of effective therapeutic or preventive approaches inducing robust tolerance toward allergens remains an unmet goal. Several experimental tolerance approaches have been described. The therapeutic use of regulatory T cells (Tregs) and the establishment of molecular chimerism are two cell-based strategies that are of particular interest. Treg therapy is close to clinical application, but its efficacy remains to be fully defined. Recent proof-of-concept studies demonstrated that transplantation of syngeneic hematopoietic stem cells modified in vitro to express a major allergen leads to molecular chimerism and robust allergen-specific tolerance. Here we review cell-based tolerance strategies in allergy, discussing their potentials and limitations.

Background: Expression of allergens in human cells is a prerequisite for the development of antigen-specific cell therapy in IgE-mediated allergy. We developed a strategy how the clinically relevant major grass pollen allergen Phl p 5 can be efficiently secreted or expressed on the surface of human cells with preserved allergenic activity., Methods: The cDNA of Phl p 5 was fused to a leader peptide with or without a transmembrane domain and both constructs were ligated into a mammalian expression vector. Transfection of these plasmids into human cells resulted in a membrane-anchored or secreted version of Phl p 5, respectively, as determined by ELISA or flow cytometric analysis., Results: Both the secreted and membrane-anchored Phl p 5 proteins bound IgE from allergic patients in an immunoblot assay and induced specific histamine release and CD203c upregulation in basophils of grass pollen-allergic patients. Proliferation of peripheral blood mononuclear cells from Phl p 5-allergic individuals was induced upon stimulation with both variants of Phl p 5 expressed in human cells similar to recombinant Phl p 5., Conclusions: Secreted and membrane-anchored Phl p 5 expressed in human cells preserved B cell as well as T cell epitopes and may be used to develop and test various cell-based strategies for allergen-specific immunomodulation and to delineate the tolerance mechanisms involved therein., (Copyright © 2011 S. Karger AG, Basel.)

Immunoglobulin-E-mediated allergy (type I allergy) is a T-helper-2-mediated disease with increasing prevalence in industrialized countries. Immunotherapy is available as causative treatment, but an effective preventive strategy is still an unmet need. Molecular chimerism is an attractive experimental approach that induces tolerance through transplantation of autologous hematopoietic stem cells that are genetically modified to express the disease-causing antigen(s). Molecular chimerism leads to permanent and robust tolerance in experimental models of autoimmune diseases and organ transplantation. Recently, proof-of-principle studies demonstrated that a type I allergic immune response can be durably tolerized by transplantation of allergen-expressing syngeneic bone marrow. We review the concept of tolerance induction through chimerism and discuss the potential of this strategy in immunoglobulin-E-mediated allergy.

Allergy represents a hypersensitivity disease that affects >25% of the population in industrialized countries. The underlying type I allergic immune reaction occurs in predisposed atopic individuals in response to otherwise harmless Ags (i.e., allergens) and is characterized by the production of allergen-specific IgE, an allergen-specific T cell response, and the release of biologically active mediators such as histamine from mast cells and basophils. Regimens permanently tolerizing an allergic immune response still need to be developed. We therefore retrovirally transduced murine hematopoietic stem cells to express the major grass pollen allergen Phl p 5 on their cell membrane. Transplantation of these genetically modified hematopoietic stem cells led to durable multilineage molecular chimerism and permanent immunological tolerance toward the introduced allergen at the B cell, T cell, and effector cell levels. Notably, Phl p 5-specific serum IgE and IgG remained undetectable, and T cell nonresponsiveness persisted throughout follow-up (40 wk). Besides, mediator release was specifically absent in in vitro and in vivo assays. B cell, T cell, and effector cell responses to an unrelated control allergen (Bet v 1) were unperturbed, demonstrating specificity of this tolerance protocol. We thus describe a novel cell-based strategy for the prevention of allergy.