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1.
Front Trop Dis ; 42024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38500783

RESUMO

The parasitic worm-derived immunomodulator, ES-62 rescues defective levels of IL-10-producing regulatory B cells (Bregs) and suppresses chronic Th1/Th17-driven inflammation to protect against joint destruction in the mouse collagen-induced arthritis (CIA) model of rheumatoid arthritis. Such autoimmune arthritis is also associated with dysbiosis of the gut microbiota and disruption of intestinal barrier integrity. We recently further exploited the CIA model to show that ES-62's prevention of joint destruction is associated with protection of intestinal barrier integrity and normalization of the gut microbiota, thereby suppressing the gut pathology that precedes the onset of autoimmunity and joint damage in CIA-mice. As the status of the gut microbiota impacts on immune responses by influencing haematopoiesis, we have therefore investigated whether ES-62 harnesses the homeostatic mechanisms regulating this gut-bone marrow (BM) axis to resolve the chronic inflammation promoting autoimmunity and joint destruction in CIA. Reflecting this, ES-62 was found to counteract the BM myeloid/lymphoid bias typically associated with chronic inflammation and infection. This was achieved primarily by ES-62 acting to maintain the levels of lymphoid lineages (B220+ and CD3+ cells) observed in naïve, healthy mice but lost from the BM of CIA-mice. Moreover, ES-62's ability to prevent bone-destroying osteoclastogenesis was found to be associated with its suppression of CIA-induced upregulation of osteoclast progenitors (OCPs) in the BM. Critically, and supporting ES-62's targeting of the gut-BM axis, this rewiring of inflammatory haematopoiesis was lost in mice with a depleted microbiome. Underlining the importance of ES-62's actions in restoring steady-state haematopoiesis, the BM levels of B and T lymphoid cells were shown to be inversely correlated, whilst the levels of OCPs positively correlated, with the severity of joint damage in CIA-mice.

2.
Front Immunol ; 14: 1285069, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38077318

RESUMO

Mice develop pathology in the lungs as they age and this may be accelerated by a high calorie diet (HCD). ES-62 is a protein secreted by the parasitic worm Acanthocheilonema viteae that is immunomodulatory by virtue of covalently attached phosphorylcholine (PC) moieties. In this study, we show that weekly treatment of C57BL/6J mice with ES-62 protected against pathology in the lungs in male but not female mice fed a HCD from 10 weeks of age as shown by reductions in cellular infiltration and airway remodelling, particularly up to 160 days of age. ES-62 also reduced gene expression of the cytokines IL-4 and IL-17 and in addition the TLR/IL-1R adaptor MyD88, in the lungs of male mice although HCD-induced increases in these inflammatory markers were not detected until between 340 and 500 days of age. A combination of two drug-like ES-62 PC-based small molecule analogues (SMAs), produced broadly similar protective effects in the lungs of male mice with respect to both lung pathology and inflammatory markers, in addition to a decrease in HCD-induced IL-5 expression. Overall, our data show that ES-62 and its SMAs offer protection against HCD-accelerated pathological changes in the lungs during ageing. Given the targeting of Th2 cytokines and IL-17, we discuss this protection in the context of ES-62's previously described amelioration of airway hyper-responsiveness in mouse models of asthma.


Assuntos
Acanthocheilonema , Interleucina-17 , Masculino , Animais , Camundongos , Interleucina-17/metabolismo , Camundongos Endogâmicos C57BL , Citocinas/metabolismo , Obesidade , Envelhecimento , Pulmão/metabolismo
3.
Bone Jt Open ; 4(11): 889-899, 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37992738

RESUMO

Aims: To perform an incremental cost-utility analysis and assess the impact of differential costs and case volume on the cost-effectiveness of robotic arm-assisted unicompartmental knee arthroplasty (rUKA) compared to manual (mUKA). Methods: This was a five-year follow-up study of patients who were randomized to rUKA (n = 64) or mUKA (n = 65). Patients completed the EuroQol five-dimension questionnaire (EQ-5D) preoperatively, and at three months and one, two, and five years postoperatively, which was used to calculate quality-adjusted life years (QALYs) gained. Costs for the primary and additional surgery and healthcare costs were calculated. Results: rUKA was associated with a relative 0.012 QALY gain at five years, which was associated with an incremental cost per QALY of £13,078 for a unit undertaking 400 cases per year. A cost per QALY of less than £20,000 was achieved when ≥ 300 cases were performed per year. However, on removal of the cost for a revision for presumed infection (mUKA group, n = 1) the cost per QALY was greater than £38,000, which was in part due to the increased intraoperative consumable costs associated with rUKA (£626 per patient). When the absolute cost difference (operative and revision costs) was less than £240, a cost per QALY of less than £20,000 was achieved. On removing the cost of the revision for infection, rUKA was cost-neutral when more than 900 cases per year were undertaken and when the consumable costs were zero. Conclusion: rUKA was a cost-effective intervention with an incremental cost per QALY of £13,078 at five years, however when removing the revision for presumed infection, which was arguably a random event, this was no longer the case. The absolute cost difference had to be less than £240 to be cost-effective, which could be achieved by reducing the perioperative costs of rUKA or if there were increased revision costs associated with mUKA with longer follow-up.

4.
Sci Data ; 10(1): 680, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37798274

RESUMO

European ash, Fraxinus excelsior is facing the double threat of ongoing devastation by the invasive fungal pathogen, Hymenoscyphus fraxineus and the imminent arrival of the non-native emerald ash borer (EAB), Agrilus planipennis. The spread of EAB which is currently moving westwards from European Russia and Ukraine into central Europe, poses an additional substantial threat to European ash, F. excelsior. While the molecular basis for resistance or variation in resistance among European ash genotypes is heavily investigated, comparatively little is known about the molecular ash traits involved in resistance against EAB. In this study we have gathered transcriptomic data from EAB inoculated genotypes of F. excelsior that have previously shown different levels of susceptibility to EAB. Resultant datasets show differential gene expression in susceptible and resistant genotypes in response to EAB infestation. This data will provide important information on the molecular basis of resistance to the EAB and allow the development of management plans to combat a pending threat of a culturally and ecologically important European tree species.


Assuntos
Besouros , Fraxinus , Transcriptoma , Animais , Fraxinus/genética , Perfilação da Expressão Gênica , Genótipo
5.
Arthritis Rheumatol ; 75(12): 2148-2160, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37410754

RESUMO

OBJECTIVE: IĸB protein B cell lymphoma 3-encoded protein (BCL3) is a regulator of the NF-κB family of transcription factors. NF-κB signaling fundamentally influences the fate of bone-forming osteoblasts and bone-resorbing osteoclasts, but the role of BCL3 in bone biology has not been investigated. The objective of this study was to evaluate BCL3 in skeletal development, maintenance, and osteoarthritic pathology. METHODS: To assess the contribution of BCL3 to skeletal homeostasis, neonatal mice (n = 6-14) lacking BCL3 (Bcl3-/- ) and wild-type (WT) controls were characterized for bone phenotype and density. To reveal the contribution to bone phenotype by the osteoblast compartment in Bcl3-/- mice, transcriptomic analysis of early osteogenic differentiation and cellular function (n = 3-7) were assessed. Osteoclast differentiation and function in Bcl3-/- mice (n = 3-5) was assessed. Adult 20-week Bcl3-/- and WT mice bone phenotype, strength, and turnover were assessed. A destabilization of the medial meniscus model of osteoarthritic osteophytogenesis was used to understand adult bone formation in Bcl3-/- mice (n = 11-13). RESULTS: Evaluation of Bcl3-/- mice revealed congenitally increased bone density, long bone dwarfism, increased bone biomechanical strength, and altered bone turnover. Molecular and cellular characterization of mesenchymal precursors showed that Bcl3-/- cells displayed an accelerated osteogenic transcriptional profile that led to enhanced differentiation into osteoblasts with increased functional activity, which could be reversed with a mimetic peptide. In a model of osteoarthritis-induced osteophytogenesis, Bcl3-/- mice exhibited decreased pathological osteophyte formation (P < 0.05). CONCLUSION: Cumulatively, these findings demonstrate that BCL3 controls developmental mineralization to enable appropriate bone formation, whereas in a pathological setting, it contributes to skeletal pathology.


Assuntos
Proteína 3 do Linfoma de Células B , Osso e Ossos , Osteogênese , Animais , Camundongos , Osso e Ossos/metabolismo , Densidade Óssea , Diferenciação Celular , NF-kappa B/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Proteína 3 do Linfoma de Células B/genética
6.
Int Orthop ; 47(7): 1765-1770, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37039819

RESUMO

PURPOSE: This study was to evaluate the survivorship of HTO for the treatment of medial compartment osteoarthritis (OA) in young and active patients from two teaching hospitals in a single city. METHODS: This is a retrospective cohort multicenter study looking at HTO for treatment of medial compartment OA. We analyzed a case series of HTO's performed by four surgeons in two centres over a 14-year period. Failure was defined as conversion to total knee replacement (TKR). All cases where additional procedures for instability of the knee were performed at the time of the index surgery were excluded. Time to failure was recorded, and a Kaplan-Meir (KM) analysis was performed to evaluate survivorship. Univariate binary regression analysis was undertaken to identify associations between risk factors and failure. RESULTS: A total of 96 patients were included in the study with a median age was 45 years. The survivorship at five years post-op was 90.3%, and at ten years post-op, it was 82%. Patients that were 14 years after surgery had a survivorship of 65%. Also, 18.8% of patients required the removal of their metalwork. The overall complication rate was 6.3%. The univariate regression analysis showed that higher age (p = 0.02) and larger corrections requiring the use of bone graft increased the risk of failure (p = 0.02). There was no statistically significant correlation between laterality, gender, complication rate, and pre-operative alignment to survivorship. CONCLUSION: This is one of the largest reported case series of HTO's with comparable survivorship at five and ten year follow-up compared to the reported literature. There was an association found between increasing age and larger corrections requiring bone graft at index procedure to increasing failure rate.


Assuntos
Osteoartrite do Joelho , Humanos , Pessoa de Meia-Idade , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/etiologia , Estudos Retrospectivos , Seguimentos , Sobrevivência , Tíbia/cirurgia , Articulação do Joelho/cirurgia , Osteotomia/efeitos adversos , Osteotomia/métodos , Resultado do Tratamento
7.
Knee Surg Sports Traumatol Arthrosc ; 31(3): 751-759, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36166095

RESUMO

PURPOSE: Computer-assisted surgery (CAS) total knee arthroplasty (TKA) remains a controversial area of surgical practice. The aim of this study is to report the ten-year revision rates and patient-reported outcome measures (PROMS) of a single-blinded, prospective, randomised controlled trial comparing electromagnetically (EM) navigated and conventional TKA. METHODS: 199 patients were randomised to receive either EM navigated or conventional TKA where the aim of implantation was neutral mechanical alignment in all cases. Ten-year revision rates were collated and compared between the two intervention groups. Longitudinal PROMS data was collected prospectively at various time points up to 10 years post-operatively. RESULTS: Over the ten-year period, there were 23 deaths (22.8%) in the EM navigation cohort and 30 deaths (30.6%) in the conventional cohort. At 10 years post-operatively, there was no statistically significant difference in all cause revision between the EM navigation and conventional cohort (4.0 vs 6.1%, p = 0.429). When analysing causes of revision that might be influenced by utilising EM navigation, there was no statistically significant difference in revisions (3.0% EM navigated vs 4.1% conventional group, p = 0.591). Patients that received navigated TKAs had improved Oxford Knee Society, American Knee Society Score and range of motion at 3 months following surgery compared to conventional TKA (p = 0.002, p = 0.032, and p = 0.05, respectively). However, from 1 to 10 years post-operatively, both interventions had equivalent outcomes. CONCLUSION: There is no difference in revision rates or clinical outcomes comparing EM navigated versus conventional TKA at ten-year follow-up. The expected mortality rate makes it unlikely that a difference in revision rates will reach statistical significance in the future. In the setting of an experienced knee arthroplasty surgeon, it is difficult to justify the additional costs of CAS in TKA surgery. LEVEL OF EVIDENCE: I.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Cirurgia Assistida por Computador , Humanos , Artroplastia do Joelho/métodos , Estudos Prospectivos , Resultado do Tratamento , Articulação do Joelho/cirurgia , Cirurgia Assistida por Computador/métodos , Osteoartrite do Joelho/cirurgia
8.
Front Immunol ; 13: 953053, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105811

RESUMO

Despite significant increases in human lifespan over the last century, adoption of high calorie diets (HCD) has driven global increases in type-2 diabetes, obesity and cardiovascular disease, disorders precluding corresponding improvements in healthspan. Reflecting that such conditions are associated with chronic systemic inflammation, evidence is emerging that infection with parasitic helminths might protect against obesity-accelerated ageing, by virtue of their evolution of survival-promoting anti-inflammatory molecules. Indeed, ES-62, an anti-inflammatory secreted product of the filarial nematode Acanthocheilonema viteae, improves the healthspan of both male and female C57BL/6J mice undergoing obesity-accelerated ageing and also extends median lifespan in male animals, by positively impacting on inflammatory, adipose metabolic and gut microbiome parameters of ageing. We therefore explored whether ES-62 affects the osteoimmunology axis that integrates environmental signals, such as diet and the gut microbiome to homeostatically regulate haematopoiesis and training of immune responses, which become dysregulated during (obesity-accelerated) ageing. Of note, we find sexual dimorphisms in the decline in bone health, and associated dysregulation of haematopoiesis and consequent peripheral immune responses, during obesity-accelerated ageing, highlighting the importance of developing sex-specific anti-ageing strategies. Related to this, ES-62 protects trabecular bone structure, maintaining bone marrow (BM) niches that counter the ageing-associated decline in haematopoietic stem cell (HSC) functionality highlighted by a bias towards myeloid lineages, in male but not female, HCD-fed mice. This is evidenced by the ability of ES-62 to suppress the adipocyte and megakaryocyte bias and correspondingly promote increases in B lymphocytes in the BM. Furthermore, the consequent prevention of ageing-associated myeloid/lymphoid skewing is associated with reduced accumulation of inflammatory CD11c+ macrophages and IL-1ß in adipose tissue, disrupting the perpetuation of inflammation-driven dysregulation of haematopoiesis during obesity-accelerated ageing in male HCD-fed mice. Finally, we report the ability of small drug-like molecule analogues of ES-62 to mimic some of its key actions, particularly in strongly protecting trabecular bone structure, highlighting the translational potential of these studies.


Assuntos
Proteínas de Helminto , Helmintos , Envelhecimento , Animais , Anti-Inflamatórios , Modelos Animais de Doenças , Feminino , Helmintos/metabolismo , Humanos , Inflamação , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade
9.
Bone Joint J ; 104-B(4): 433-443, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35360949

RESUMO

AIMS: The aim of this study was to compare any differences in the primary outcome (biphasic flexion knee moment during gait) of robotic arm-assisted bi-unicompartmental knee arthroplasty (bi-UKA) with conventional mechanically aligned total knee arthroplasty (TKA) at one year post-surgery. METHODS: A total of 76 patients (34 bi-UKA and 42 TKA patients) were analyzed in a prospective, single-centre, randomized controlled trial. Flat ground shod gait analysis was performed preoperatively and one year postoperatively. Knee flexion moment was calculated from motion capture markers and force plates. The same setup determined proprioception outcomes during a joint position sense test and one-leg standing. Surgery allocation, surgeon, and secondary outcomes were analyzed for prediction of the primary outcome from a binary regression model. RESULTS: Both interventions were shown to be effective treatment options, with no significant differences shown between interventions for the primary outcome of this study (18/35 (51.4%) biphasic TKA patients vs 20/31 (64.5%) biphasic bi-UKA patients; p = 0.558). All outcomes were compared to an age-matched, healthy cohort that outperformed both groups, indicating residual deficits exists following surgery. Logistic regression analysis of primary outcome with secondary outcomes indicated that the most significant predictor of postoperative biphasic knee moments was preoperative knee moment profile and trochlear degradation (Outerbridge) (R2 = 0.381; p = 0.002, p = 0.046). A separate regression of alignment against primary outcome indicated significant bi-UKA femoral and tibial axial alignment (R2 = 0.352; p = 0.029), and TKA femoral sagittal alignment (R2 = 0.252; p = 0.016). The bi-UKA group showed a significant increased ability in the proprioceptive joint position test, but no difference was found in more dynamic testing of proprioception. CONCLUSION: Robotic arm-assisted bi-UKA demonstrated equivalence to TKA in achieving a biphasic gait pattern after surgery for osteoarthritis of the knee. Both treatments are successful at improving gait, but both leave the patients with a functional limitation that is not present in healthy age-matched controls. Cite this article: Bone Joint J 2022;103-B(4):433-443.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho , Procedimentos Cirúrgicos Robóticos , Artroplastia do Joelho/efeitos adversos , Humanos , Articulação do Joelho/cirurgia , Estudos Prospectivos
10.
Curr Res Microb Sci ; 3: 100102, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35005660

RESUMO

Brenneria goodwinii, Rahnella victoriana and Gibbsiella quercinecans are three bacterial species frequently isolated together from oak displaying symptoms of Acute Oak Decline (AOD), which include weeping patches on trunks. All three bacterial species play a role in lesion formation in the current episode of AOD in Britain, although B. goodwinii is the most dominant. The ongoing research into stem lesion formation characteristic of this polybacterial syndrome has been focussed primarily on the pathogenicity, identification and taxonomy of these bacteria. As all three species were newly classified within the past ten years, there are many unanswered questions regarding their ecology and interactions with each other. To determine the effect of bacterial interactions on fitness in vitro, we examined pairwise (diculture) and multispecies (triculture) interactions between B. goodwinii, R. victoriana and G. quercinecans in oak leaf media microcosms. Additionally, the effect of co-culturing on the evolution of these species was determined and the evolved B. goodwinii strains were examined further by whole genome sequencing. Our results indicate that B. goodwinii thrived in monoculture with significantly higher viable cell counts than the other two species. Additionally, B. goodwinii performed well in pairwise culture with mutually competitive interactions observed between B. goodwinii and R. victoriana, and between B. goodwinii and G. quercinecans. In the multispecies triculture, B. goodwinii and R. victoriana appeared to exhibit co-ordinated behaviour to outcompete G. quercinecans. After four weeks B. goodwinii grown in co-culture with the other two species developed greater evolved fitness than the strain grown in monoculture as reflected by the increased viable cell counts. The competitive interactions taking place between the threes species indicated evolving improved fitness of B. goodwinii in vitro, that gave it a growth advantage over both R. victoriana and G. quercinecans which showed no significant changes in fitness. Overall, B. goodwinii gains greater benefit in terms of fitness from in vitro competitive interaction with the other two species.

11.
Eur J Orthop Surg Traumatol ; 32(8): 1591-1599, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34628535

RESUMO

INTRODUCTION: Limb-sparing surgery with negative margins is possible in most soft tissue sarcoma (STS) resections and focuses on maximising function and minimising morbidity. Various risk factors for surgical site infections (SSIs) have been reported in the literature specific to sarcoma surgery. The aim of this study is to determine whether systemic inflammatory response prognostic scoring systems can predict post-operative SSI in patients undergoing potentially curative resection of STS. METHODS: Patients who had a planned curative resection of a primary STS at a single centre between January 2010 and December 2019 with a minimum follow-up of 6 months were included. Data were extracted on patient and tumour characteristics, and pre-operative blood results were used to calculate inflammatory prognostic scores based on published thresholds and correlated with risk of developing SSI or debridement procedures. RESULTS: A total of 187 cases were included. There were 60 SSIs. On univariate analysis, there was a statistically significant increased risk of SSI in patients who are diabetic, increasing specimen diameter, American Society of Anaesthesiology (ASA) grade 3, use of endoprosthetic replacement, blood loss greater than 1 L, and junctional tumour location. Modified Glasgow prognostic score, C-reactive protein/albumin ratio and neutrophil-platelet score (NPS) were statistically associated with the risk of SSI. On multivariate analysis, ASA grade 3, junctional tumour location and NPS were independently associated with the risk of developing a SSI. CONCLUSION: This study supports the routine use of simple inflammation-based prognostic scores in identifying patients at increased risk of developing infectious complications in patients undergoing potentially curative resection of STS.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/etiologia , Prognóstico , Proteína C-Reativa , Sarcoma/cirurgia , Sarcoma/patologia , Neoplasias de Tecidos Moles/cirurgia , Neoplasias de Tecidos Moles/patologia , Fatores de Risco , Estudos Retrospectivos
12.
Bone Joint J ; 104-B(1): 168-176, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34969280

RESUMO

AIMS: The modified Glasgow Prognostic Score (mGPS) uses preoperative CRP and albumin to calculate a score from 0 to 2 (2 being associated with poor outcomes). mGPS is validated in multiple carcinomas. To date, its use in soft-tissue sarcoma (STS) is limited, with only small cohorts reporting that increased mGPS scores correlates with decreased survival in STS patients. METHODS: This retrospective multicentre cohort study identified 493 STS patients using clinical databases from six collaborating hospitals in three countries. Centres performed a retrospective data collection for patient demographics, preoperative blood results (CRP and albumin levels and neutrophil, leucocyte, and platelets counts), and oncological outcomes (disease-free survival, local, or metastatic recurrence) with a minimum of two years' follow-up. RESULTS: We found that increased mGPS, tumour size, grade, neutrophil/lymphocyte ratio, and disease recurrence were associated with reduced survival. Importantly, mGPS was the best at stratifying prognosis and could be used in conjunction with tumour grade to sub-stratify patient survival. CONCLUSION: This study demonstrated that prognosis of localized STS strongly correlates with mGPS, as an increasing score is associated with a poorer outcome. We note that 203 patients (41%) with an STS have evidence of systemic inflammation. We recommend the mGPS and other biochemical blood indicators be introduced into the routine diagnostic assessment in STS patients to stratify patient prognosis. Its use will support clinical decision-making, especially when morbid treatment options such as amputation are being considered. Cite this article: Bone Joint J 2022;104-B(1):168-176.


Assuntos
Sarcoma/sangue , Sarcoma/cirurgia , Adulto , Idoso , Biomarcadores Tumorais/análise , Contagem de Células Sanguíneas , Proteína C-Reativa/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/patologia , Albumina Sérica/análise , Análise de Sobrevida
13.
Bone Jt Open ; 2(12): 1049-1056, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34905941

RESUMO

AIMS: The primary objective of this study was to compare the postoperative infection rate between negative pressure wound therapy (NPWT) and conventional dressings for closed incisions following soft-tissue sarcoma (STS) surgery. Secondary objectives were to compare rates of adverse wound events and functional scores. METHODS: In this prospective, single-centre, randomized controlled trial (RCT), patients were randomized to either NPWT or conventional sterile occlusive dressings. A total of 17 patients, with a mean age of 54 years (21 to 81), were successfully recruited and none were lost to follow-up. Wound reviews were undertaken to identify any surgical site infection (SSI) or adverse wound events within 30 days. The Toronto Extremity Salvage Score (TESS) and Musculoskeletal Tumor Society (MSTS) score were recorded as patient-reported outcome measures (PROMs). RESULTS: There were two out of seven patients in the control group (28.6%), and two out of ten patients in the intervention group (20%) who were diagnosed with a SSI (p > 0.999), while one additional adverse wound event was identified in the control group (p = 0.593). No significant differences in PROMs were identified between the groups at either 30 days (TESS, p = 0.987; MSTS, p = 0.951) or six-month (TESS, p = 0.400) follow-up. However, neoadjuvant radiotherapy was significantly associated with a SSI within 30 days of surgery, across all patients (p = 0.029). The mean preoperative modified Glasgow Prognostic Score (mGPS) was also significantly higher among patients who developed a postoperative adverse wound event (p = 0.028), including a SSI (p = 0.008), across both groups. CONCLUSION: This is the first RCT comparing NPWT with conventional dressings following musculoskeletal tumour surgery. Postoperative wound complications are common in this group of patients and we observed an overall SSI rate of 23.5%. We propose proceeding to a multicentre trial, which will help more clearly define the role of closed incision NPWT in STS surgery. Cite this article: Bone Jt Open 2021;2(12):1049-1056.

14.
Bone Joint J ; 103-B(10): 1561-1570, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34587803

RESUMO

AIMS: The aim of this study was to compare the clinical outcomes of robotic arm-assisted bi-unicompartmental knee arthroplasty (bi-UKA) with conventional mechanically aligned total knee arthroplasty (TKA) during the first six weeks and at one year postoperatively. METHODS: A per protocol analysis of 76 patients, 43 of whom underwent TKA and 34 of whom underwent bi-UKA, was performed from a prospective, single-centre, randomized controlled trial. Diaries kept by the patients recorded pain, function, and the use of analgesics daily throughout the first week and weekly between the second and sixth weeks. Patient-reported outcome measures (PROMs) were compared preoperatively, and at three months and one year postoperatively. Data were also compared longitudinally and a subgroup analysis was conducted, stratified by preoperative PROM status. RESULTS: Both operations were shown to offer comparable outcomes, with no significant differences between the groups across all timepoints and outcome measures. Both groups also had similarly low rates of complications. Subgroup analysis for preoperative psychological state, activity levels, and BMI showed no difference in outcomes between the two groups. CONCLUSION: Robotic arm-assisted, cruciate-sparing bi-UKA offered similar early clinical outcomes and rates of complications to a mechanically aligned TKA, both in the immediate postoperative period and up to one year following surgery. Further work is required to identify which patients with osteoarthritis of the knee will derive benefit from a cruciate-sparing bi-UKA. Cite this article: Bone Joint J 2021;103-B(10):1561-1570.


Assuntos
Artroplastia do Joelho/métodos , Hemiartroplastia/métodos , Osteoartrite do Joelho/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Artroplastia do Joelho/instrumentação , Método Duplo-Cego , Feminino , Seguimentos , Marcha , Hemiartroplastia/instrumentação , Humanos , Análise de Intenção de Tratamento , Prótese do Joelho , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Resultado do Tratamento
15.
Int Orthop ; 45(11): 2859-2867, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34392378

RESUMO

PURPOSE: The NexGen Legacy Posterior Stabilised (LPS) prosthesis (Zimmer Biomet, Warsaw, IN, USA) has augmentable and non-augmentable tibial baseplate options. We have noted an anecdotal increase in the number of cases requiring early revision for aseptic loosening since adopting the non-augmentable option. The purpose of this study was to ascertain our rates of aseptic tibial loosening for the two implant types within five years of implantation and to investigate the causes for any difference observed. METHODS: A database search was performed for all patients who underwent primary total knee arthroplasty (TKA) using the NexGen LPS between 2009 and 2015. Kaplan-Meier curves were plotted to assess for differences in revision rates between cohorts. We collected and compared data on gender, age, body mass index, component alignment and cement mantle quality as these were factors thought to affect the likelihood of aseptic loosening. RESULTS: Two thousand one hundred seventy-two TKAs were included with five year follow-up. There were 759 augmentable knees of which 14 were revised and 1413 non-augmentable knees of which 48 were revised. The overall revision rate at five years was 1.84% in the augmentable cohort and 3.4% in the non-augmentable cohort. The revision rate for aseptic loosening was 0.26% in the augmentable group and 1.42% in the non-augmentable group (p = 0.0241). CONCLUSIONS: We have identified increased rates of aseptic loosening in non-augmentable components. This highlights the effect that minor implant changes can have on outcomes. We recommend that clinicians remain alert to implant changes and publish their own results when important trends are observed.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Artroplastia do Joelho/efeitos adversos , Humanos , Articulação do Joelho/cirurgia , Prótese do Joelho/efeitos adversos , Desenho de Prótese , Falha de Prótese , Reoperação , Estudos Retrospectivos
16.
J Arthroplasty ; 36(10): 3451-3455, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34226082

RESUMO

BACKGROUND: The objective of this study is to provide the 5-year follow-up results of a randomized study comparing conventional versus electromagnetic computer navigated total knee arthroplasty. METHODS: Analysis of 127 patients (66 navigated and 61 conventional surgeries) was performed from a prospective, single-blinded, randomized controlled trial. Patient-reported outcome measures were collected at 5 years after surgery and compared with previously published 1-year clinical outcomes. Five-year surgical revision rates were collated and compared between intervention groups. RESULTS: Overall, there have been continued improvements in the clinical scores of patients in both groups when compared with clinical data at 1 year; however, at 5 years, there is no statistical difference in any of the patient-reported outcome measures between conventional and navigated surgery. Interestingly, improved implant survivorship was observed in the navigated (0% revision rate) compared with the conventional group (4.9% all-cause revision rate). CONCLUSION: Electromagnetic computer navigated technology produces similar clinical outcomes compared with traditional surgery. Further work is required to monitor implant survivorship, and clinical outcomes with long-term follow-up, to determine the cost effectiveness of this technology.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Cirurgia Assistida por Computador , Fenômenos Eletromagnéticos , Seguimentos , Humanos , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Estudos Prospectivos , Falha de Prótese , Método Simples-Cego , Resultado do Tratamento
17.
Bone Joint J ; 103-B(6): 1088-1095, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34058870

RESUMO

AIMS: Unicompartmental knee arthroplasty (UKA) is a bone-preserving treatment option for osteoarthritis localized to a single compartment in the knee. The success of the procedure is sensitive to patient selection and alignment errors. Robotic arm-assisted UKA provides technological assistance to intraoperative bony resection accuracy, which is thought to improve ligament balancing. This paper presents the five-year outcomes of a comparison between manual and robotically assisted UKAs. METHODS: The trial design was a prospective, randomized, parallel, single-centre study comparing surgical alignment in patients undergoing UKA for the treatment of medial compartment osteoarthritis (ISRCTN77119437). Participants underwent surgery using either robotic arm-assisted surgery or conventional manual instrumentation. The primary outcome measure (surgical accuracy) has previously been reported, and, along with secondary outcomes, were collected at one-, two-, and five-year timepoints. Analysis of five-year results and longitudinal analysis for all timepoints was performed to compare the two groups. RESULTS: Overall, 104 (80%) patients of the original 130 who received surgery were available at five years (55 robotic, 49 manual). Both procedures reported successful results over all outcomes. At five years, there were no statistical differences between the groups in any of the patient reported or clinical outcomes. There was a lower reintervention rate in the robotic arm-assisted group with 0% requiring further surgery compared with six (9%) of the manual group requiring additional surgical intervention (p < 0.001). CONCLUSION: This study has shown excellent clinical outcomes in both groups with no statistical or clinical differences in the patient-reported outcome measures. The notable difference was the lower reintervention rate at five years for roboticarm-assisted UKA when compared with a manual approach. Cite this article: Bone Joint J 2021;103-B(6):1088-1095.


Assuntos
Artroplastia do Joelho/métodos , Osteoartrite do Joelho/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Atividades Cotidianas , Adulto , Idoso , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medição da Dor , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Complicações Pós-Operatórias , Estudos Prospectivos , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Reoperação/estatística & dados numéricos
18.
3 Biotech ; 11(6): 286, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34094805

RESUMO

Russian olive (Elaeagnus angustifolia) is an economically important ornamental and crop plant. It has a wide range of biologically active compounds and is regarded as a unique medicinal plant with multiple applications. Members of the order Enterobacteriales isolated from trees are often associated with bacterial canker. During the growing season from 2017 to 2020, forty Gram-negative bacterial strains were isolated from Russian olive trees infected with cankers showing symptoms such as distinctive lesions on the trunk and branches, decline, weakness of trees, cracked bark, depressed brown to black lesions accompanied by exudation of gum, in the Kerman and Mazandaran Provinces of Iran. We used a polyphasic approach to identify and characterize these strains. Using a multilocus sequence analysis approach of four housekeeping loci, namely atpD, rpoB, gyrB, infB, and partial 16S rRNA gene sequences, isolates were identified as Gibbsiella quercinecans. These results were further supported by phenotypic and biochemical tests. Results of the biochemical, physiological and phenotypic experiments, indicated that the isolates are members of the Enterobacteriales and within the genus Gibbsiella. Pathogenicity of the G. quercinecans isolates was confirmed by fulfillment of Koch's postulates. To our knowledge, this is the first report of G. quercinecans as the causal agent of bacterial canker of Russian olive trees.

19.
Parasite Immunol ; 43(3): e12803, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33091157

RESUMO

AIMS: ES-62 is a well-studied anti-inflammatory molecule secreted by L4-adult stage Acanthocheilonema viteae. We maintain the life cycle of A viteae using Meriones libycus as the definitive host. Here, we investigated whether the full life cycle could be maintained, and functional ES-62 produced, in a related jird species-Meriones shawi. METHODS AND RESULTS: Adult worms were produced in comparable numbers in the two species, but very few microfilariae (MF) were observed in the M shawi bloodstream. M shawi ES-62 produced ex vivo was functional and protective in a mouse model of arthritis. Myeloid-derived cells from naïve and infected jirds of both species were compared with respect to ROS production and osteoclast generation, and some differences between the two species in both the absence and presence of infection were observed. CONCLUSIONS: The life cycle of A viteae cannot be successfully completed in M shawi jirds but L3 stage worms develop to adulthood and produce functional ES-62. Preliminary investigation into jird immune responses suggests that infection can differentially modulate myeloid responses in the two species. However, species-specific reagents are required to understand the complex interplay between A viteae and its host and to explain the lack of circulating MF in infected M shawi jirds.


Assuntos
Acanthocheilonema/crescimento & desenvolvimento , Acantoqueilonemíase/parasitologia , Gerbillinae/parasitologia , Proteínas de Helminto/biossíntese , Animais , Modelos Animais de Doenças , Feminino , Estágios do Ciclo de Vida , Masculino , Camundongos , Microfilárias/crescimento & desenvolvimento , Especificidade da Espécie
20.
Bone Joint J ; 102-B(11): 1511-1518, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33135443

RESUMO

AIMS: The aim of this study was to compare robotic arm-assisted bi-unicompartmental knee arthroplasty (bi-UKA) with conventional mechanically aligned total knee arthroplasty (TKA) in order to determine the changes in the anatomy of the knee and alignment of the lower limb following surgery. METHODS: An analysis of 38 patients who underwent TKA and 32 who underwent bi-UKA was performed as a secondary study from a prospective, single-centre, randomized controlled trial. CT imaging was used to measure coronal, sagittal, and axial alignment of the knee preoperatively and at three months postoperatively to determine changes in anatomy that had occurred as a result of the surgery. The hip-knee-ankle angle (HKAA) was also measured to identify any differences between the two groups. RESULTS: The pre- to postoperative changes in joint anatomy were significantly less in patients undergoing bi-UKA in all three planes in both the femur and tibia, except for femoral sagittal component orientation in which there was no difference. Overall, for the six parameters of alignment (three femoral and three tibial), 47% of bi-UKAs and 24% TKAs had a change of < 2° (p = 0.045). The change in HKAA towards neutral in varus and valgus knees was significantly less in patients undergoing bi-UKA compared with those undergoing TKA (p < 0.001). Alignment was neutral in those undergoing TKA (mean 179.5° (SD 3.2°)) while those undergoing bi-UKA had mild residual varus or valgus alignment (mean 177.8° (SD 3.4°)) (p < 0.001). CONCLUSION: Robotic-assisted, cruciate-sparing bi-UKA maintains the natural anatomy of the knee in the coronal, sagittal, and axial planes better, and may therefore preserve normal joint kinematics, compared with a mechanically aligned TKA. This includes preservation of coronal joint line obliquity. HKAA alignment was corrected towards neutral significantly less in patients undergoing bi-UKA, which may represent restoration of the pre-disease constitutional alignment (p < 0.001). Cite this article: Bone Joint J 2020;102-B(11):1511-1518.


Assuntos
Artroplastia do Joelho , Articulação do Joelho/cirurgia , Procedimentos Cirúrgicos Robóticos , Idoso , Fenômenos Biomecânicos , Mau Alinhamento Ósseo/prevenção & controle , Feminino , Fêmur/cirurgia , Humanos , Articulação do Joelho/anatomia & histologia , Prótese do Joelho , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tíbia/cirurgia
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