Nonunions of the proximal part of the humerus can be treated with reverse shoulder arthroplasty. Although clinical outcomes improved significantly, we found an unacceptably high rate of dislocations associated with intraoperative resection of the tuberosities. The tuberosities and the attached rotator cuff should be preserved if possible to reduce the risk of dislocation after reverse total shoulder arthroplasty.

BackgroundAseptic loosening (AL) of hip prosthesis presents inflammation and pain as sign and symptom similarly to arthritis pathologies. Still, the immune and innervation profiles in hip AL remain unclear and their interplay is poorly explored. Herein, local tissue inflammatory response, sensory and sympathetic innervation as well as associated local mediators were assessed in hip joint microenvironment underlying AL and compared to osteoarthritis (OA).MethodsHistopathological analysis, immune cells (macrophages, T, B cells and PMNs) as well as sensory and sympathetic nerve fibers (SP+, CGRP+, TH+) distribution and profiles were analyzed on tissues retrieved from patients with failed hip prostheses due to AL (n = 20) and hip OA (n = 15) by immunohistochemistry. Additionally, transcriptional levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-12a, iNOS), anti-inflammatory cytokine (IL-10), osteoclastic factor (RANKL) and bone remodeling factor (TGF-β1) were locally evaluated by qRT-PCR. Serum TGF-β1 levels were assessed preoperatively by ELISA.ResultsHistopathological analysis revealed that tissues, aseptic interface membranes of AL patients had distinct tissue architecture and immune cells profile when compared to OA synovial tissues. Macrophages, T cells and B cells showed significant differences in tissue distribution. In OA, inflammation is mostly confined to the vicinity of synovial membrane while in AL macrophages infiltrated throughout the tissue. This differential immune profile is also accompanied with a distinct pattern of sensory and sympathetic innervation. Importantly, in AL patients, a lack of sympathetic innervation aseptic interface membranes without compensation mechanisms at cellular levels was observed with simultaneous reorganization of sensorial innervation. Despite the different histopathological portrait, AL and OA patients exhibited similar transcriptional levels of genes encoding key proteins in local immune response. Nevertheless, in both pathologies, TGF-β1 expression was prominent in sites where the inflammation is occurring. However, at systemic level no differences were found.ConclusionThese findings indicate that AL patients exhibit different local inflammatory response and innervation signatures from OA patients in hip joint. These insights shed the light on neuro-immune interplay in AL and highlight the need to better understand this crosstalk to unravel potential mechanisms for targeted-therapies to improve hip joint lifetime and treatment.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0950-5) contains supplementary material, which is available to authorized users.

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In osteoarthritis (OA), pain is the dominant clinical symptom, yet the therapeutic approaches remain inadequate. The knowledge of the nociceptive mechanisms in OA, which will allow to develop effective therapies for OA pain, is of utmost need. In this study, we investigated the nociceptive mechanisms involved in post-traumatic OA pain, using the destabilization of the medial meniscus (DMM) mouse model. Our results revealed the development of peripheral pain sensitization, reflected by augmented mechanical allodynia. Along with the development of pain behaviour, we observed an increase in the expression of calcitonin gene-related peptide (CGRP) in both the sensory nerve fibers of the periosteum and the dorsal root ganglia. Interestingly, we also observed that other nociceptive mechanisms commonly described in non-traumatic OA phenotypes, such as infiltration of the synovium by immune cells, neuropathic mechanisms and also central sensitization were not present. Overall, our results suggest that CGRP in the sensory nervous system is underlying the peripheral sensitization observed after traumatic knee injury in the DMM model, highlighting the CGRP as a putative therapeutic target to treat pain in post-traumatic OA. Moreover, our findings suggest that the nociceptive mechanisms involved in driving pain in post-traumatic OA are considerably different from those in non-traumatic OA.

Inflammation is a common symptom in joint disorders such as rheumatoid arthritis, osteoarthritis (OA) and implant aseptic loosening (AL). The sympathetic nervous system is well known to play a critical role in regulating inflammatory conditions, and imbalanced sympathetic activity has been observed in rheumatoid arthritis. In AL it is not clear whether the sympathetic nervous system is altered. In this study we evaluated the systemic and local profile of neuroimmune molecules involved in the interplay between the sympathetic nervous system and the periprosthetic inflammation in hip AL. Our results showed that periprosthetic inflammation does not trigger a systemic response of the sympathetic nervous system, but is mirrored rather by the impairment of the sympathetic activity locally in the hip joint. Moreover, macrophages were identified as key players in the local regulation of inflammation by the sympathetic nervous system in a process that is implant debris-dependent and entails the reduction of both adrenergic and Neuropetide Y (NPY)-ergic activity. Additionally, our results showed a downregulation of semaphorin 3A (SEMA3A) that may be part of the mechanism sustaining the periprosthetic inflammation. Overall, the local sympathetic nervous system emerges as a putative target to mitigate the inflammatory response to debris release and extending the lifespan of orthopedic implants.

Despite the renewed interest in ion implantation doping of GaN, efficient electrical activation remains a challenge. The lattice location of 27Mg is investigated in GaN of different doping types as a function of implantation temperature and fluence at CERN's ISOLDE facility. The amphoteric nature of Mg is elucidated, i.e., the concurrent occupation of substitutional Ga and interstitial sites: following room temperature ultra‐low fluence (≈2 × 1010 cm−2) implantation, the interstitial fraction of Mg is highest (20–24%) in GaN pre‐doped with stable Mg during growth, and lowest (2–6%) in n‐GaN:Si, while undoped GaN shows an intermediate interstitial fraction of 10–12%. Both for p‐ and n‐GaN prolonged implantations cause interstitial 27Mg to approach the levels found for undoped GaN. Implanting above 400 °C progressively converts interstitial Mg to substitutional Ga sites due to the onset of Mg interstitial migration (estimated activation energy 1.5–2.3 eV) and combination with Ga vacancies. In all sample types, implantations above a fluence of 1014 cm−2 result in >95% substitutional Mg. Ion implantation is hence a very efficient method to introduce Mg into substitutional Ga sites, i.e., challenges toward high electrical activation of implanted Mg are not related to lack of substitutional incorporation.

BackgroundNeuroimmune axis is central in the physiopathology of hip osteoarthritis (OA), but its specific pathways are still unclear. This systematic review aims to assess the nervous and immune system profile of patients with hip osteoarthritis (OA) when compared to healthy controls.MethodsA systematic review followed PRISMA guidelines was conducted. A two-step selection process was completed, and from 609 references 17 were included. The inclusion criteria were: original articles on adult patients with hip OA, with assessment of neuroimmune expression. Articles with other interventions prior to analysis and those without a control group were excluded.ResultsThirty-nine relevant neuroimmune markers were identified, with assessments in bone, cartilage, synovial membrane, synovial fluid, whole blood, serum and/or immune cells. GM-CSF, IFN-γ, IL-1α, IL-6, IL-8, IL-1 and TNF-α presented variable expression among tissues studied when compared between hip OA and controls. VEGFs and TGF-ß isoforms showed similar tendencies among tissues and studies. On nervous expression, CGRP, Tuj-1 and SP were increased in synovial membrane. Overall, patients with hip OA presented a higher number of overexpressed markers.ConclusionsFor the first time a systematic review on neuroimmune expression in patients with hip OA found an upregulation of neuroimmune markers, with deregulated balance between pro and anti-inflammatory cytokines. However, no clear systematic pattern was found, and few information is available on nervous expression. This highlights the importance of future research with clear methodologies to guide the management of these patients.Electronic supplementary materialThe online version of this article (10.1186/s12891-017-1755-2) contains supplementary material, which is available to authorized users.

Background Microdiscectomy is the most commonly performed spine surgery and the first transitioning for outpatient settings. However, this transition was never studied, in what comes to cost-utility assessment. Accordingly, this economic study aims to access the cost-effectiveness of outpatient lumbar microdiscectomy when compared with the inpatient procedure. Methods This is a cost utility study, adopting the hospital perspective. Direct medical costs were retrieved from the assessment of 20 patients undergoing outpatient lumbar microdiscectomy and 20 undergoing inpatient lumbar microdiscectomy Quality-adjusted life-years were calculated from Oswestry Disability Index values (ODI). ODI was prospectively assessed in outpatients in pre and 3- and 6-month post-operative evaluations. Inpatient ODI data were estimated from a meta-analysis. A probabilistic sensitivity analysis was performed and incremental cost-effectiveness ratio (ICER) calculated. Results Outpatient procedure was cost-saving in all models tested. At 3-month assessment ICER ranged from €135,753 to €345,755/QALY, higher than the predefined threshold of €60,000/QALY gained. At 6-month costs were lower and utilities were higher in outpatient, overpowering the inpatient procedure. Probabilistic sensitivity analysis showed that in 65% to 73% of simulations outpatient was the better option. The savings with outpatient were about 55% of inpatient values, with similar utility scores. No 30-day readmissions were recorded in either group. Conclusion This is the first economic study on cost-effectiveness of outpatient lumbar microdiscectomy, showing a significant reduction in costs, with a similar clinical outcome, proving it cost-effective.