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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_2 | Pages 74 - 74
2 Jan 2024
Peniche Silva C Dominguez R Bakht S Pardo A Joris V Gonçalves A Texeira S Balmayor E Gomes M van Griensven M
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Tendons and tendon-to-bone entheses don't usually regenerate after injury, and the hierarchical organization of such tissues makes them challenging sites of study for tissue engineers. In this study, we have tried a novel approach using miRNA and a bioactive bioink to stimulate the regeneration of the enthesis. microRNAs (miRNAs) are short, non-coding sequences of RNA that act as post-transcriptional regulators of gene and protein expression [1]. Mimics or inhibitors of specific miRNAs can be used to restore lost functions at the cell level or improve healing at the tissue level [2,3]. We characterized the healing of a rat patellar enthesis and found that miRNA-16-5p was upregulated in the fibrotic portion of the injured tissue 10 days after the injury. Based on the reported interactions of miRNA-16-5p with the TGF-β pathway via targeting of SMAD3, we aimed to explore the effects of miRNA-16-5p mimics on the tenogenic differentiation of adipose-derived stem cells (ASCs) encapsulated in a bioactive bioink [4,5]. Bioinks with different properties are used for the 3D printing of biomimetic constructs. By integrating cells, materials, and bioactive molecules it is possible to tailor the regenerative capacity of the ink to meet the particular requirements of the tissue to engineer [5]. Here we have encapsulated ASCs in a gelatin-methacryloyl (GelMa) bioink that incorporates miR-16-5p mimics and magnetically responsive microfibers (MRFs). When the bioink is crosslinked in the presence of a magnetic field, the MRFs align unidirectionally to create an anisotropic construct with the ability to promote the tenogenic differentiation of the encapsulated ASCs. Additionally, the obtained GelMA hydrogels retained the encapsulated miRNA probes, which permitted the effective 3D transfection of the ASC and therefore, the regulation of gene expression, allowing to investigate the effects of the miR-16-5p mimics on the tenogenic differentiation of the ASCs in a biomimetic scenario.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 133 - 133
2 Jan 2024
Carvalho M Cabral J da Silva C
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Mesenchymal stromal cells (MSC) have been proposed as an emerging cell therapy for bone tissue engineering applications. However, the healing capacity of the bone tissue is often compromised by patient's age and comorbidities, such as osteoporosis. In this context, it is important to understand the impact of donor age on the therapeutic potential of MSC. Importantly, the impact on donor age is not restricted to cells themselves but also to their microenvironment that is known to affect cell function.

The extracellular matrix (ECM) has an important role in stem cell microenvironment, being able to modulate cell proliferation, self-renewal and differentiation. Decellularized cell-derived ECM (dECM) has been explored for regenerative medicine applications due to its bioactivity and its resemblance to the in vivo microenvironment. Thus, dECM offers the opportunity not only to develop microenvironments with customizable properties for improvement of cellular functions but also as a platform to study cellular niches in health and disease. In this study, we investigated the capacity of the microenvironment to rescue the impaired proliferative and osteogenic potential of aged MSC. The goal of this work was to understand if the osteogenic capacity of MSC could be modulated by exposure to a dECM derived from cells obtained from young donors. When aged MSC were cultured on dECM derived from young MSC, their in vitro proliferative and osteogenic capacities were enhanced. Our results suggest that the microenvironment, specifically the ECM, plays a crucial role in the osteogenic differentiation capacity of MSC. dECM might be a valuable clinical strategy to overcome the age-related decline in the osteogenic potential of MSC by recapitulating a younger microenvironment, attenuating the effects of aging on the stem cell niche. Overall, this study opens new possibilities for developing clinical strategies for elderly patients with limited bone formation capacity who currently lack effective treatments.

Acknowledgements: The authors thank FCT for funding through the project DentalBioMatrix (PTDC/BTM-MAT/3538/2020) and to the research institutions iBB (UIDB/04565/2020 and UIDP/04565/2020) and Associate Laboratory i4HB (LA/P/0140/2020).


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_3 | Pages 16 - 16
1 Apr 2019
Prasad KSRK Punjabi S Silva C Sarasin S Lewis P
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DAIR procedure is well established for Prosthetic Joint Infection (PJI) in acute setting after total hip and knee replacements. We present our experience of DAIR following hip and knee replacements in a District General Hospital (DGH), where we delivered comparable results to leading tertiary centres in short to mid-term followup.

We undertook a retrospective study involving 14 patients, who underwent DAIR in our DGH between August 2012 and December 2015. Patient cohort included primary, complex primary and revision hip and knee replacements. Microbiological support was provided by a Microbiologist with interest in musculoskeletal infections.

14 patients [9 males, 5 females; age 62 to 78 years (Mean 70.7); BMI 22 to 44.2 (Mean 33.8)] with multiple comorbidities underwent DAIR procedure within 3 weeks of onset of symptoms. 12 out of 14 grew positive cultures with two growing Vancomycin resistant Enterococci. Intravenous antibiotics were started after multiple samples intraoperatively and continued in six patients after discharge, while 8 were discharged with oral antibiotics. One patient died of overwhelming intraoperative septic shock in postoperative period. Another patient died of myocardial infarction subsequently. 12 (85.7%) patients were doing well with regular followup (Mean 20 months).

With good patient selection, DAIR is a far simpler solution and a safe and reproducible surgical option for early PJI following hip and knee replacements compared to one or two stage revisions. But published data in contemporary literature is predominantly from specialised centres. Our small series provides a perspective of comparable early to mid-term results of DAIR from DGH.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_5 | Pages 146 - 146
1 Apr 2019
Prasad KSRK Punjabi S Manta A Silva C Sarasin S Lewis P
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OBJECTIVE

Debridement, Antibiotics and Implant Retention (DAIR) procedure is well established for Prosthetic Joint Infection (PJI) in acute setting after total hip and knee replacements. We present our perspective of DAIR in a relatively a small cohort following hip and knee replacements in a District General Hospital (DGH) in United Kingdom, where we delivered comparable results to leading tertiary centers in short to mid-term followup.

METHODS

We undertook a retrospective study involving 14 patients, who underwent DAIR in our DGH between August 2012 and December 2015. Patient cohort included primary, complex primary and revision hip and knee replacements. Multiple samples were taken intraoperatively for cultures and histology. mMicrobiological support was provided by a microbiologist with interest in musculoskeletal infections.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_16 | Pages 20 - 20
1 Oct 2017
Punjabi S Prasad KSRK Manta A Silva C Sarasin S Lewis P
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Debridement Antibiotics Implant Retention (DAIR) is a recognised procedure in the management of acute prosthetic joint infection (PJI). We present an experience of DAIR following hip and knee replacements in a District General Hospital.

A retrospective review of 14 patients who underwent DAIR procedures between August 2012 and December 1015 were collated. The cohort included primary, complex primary and revision hip and knee replacements. All patients received multidisciplinary care with surgery performed by one of two arthroplasty surgeons.

9 males and 5 females with age 62 − 78 years (Mean 70.7) and BMI 22–44.2 (Mean 33.8) with various co-morbidities underwent DAIR. Surgical criteria required DAIR to be performed within 3 weeks of the onset of symptoms of infection. The time from index surgery however ranged from 15 days to 58 months. 12 of 14 grew positive cultures including two growing Vancomycin Resistant Enterococcus. Intravenous antibiotics were commenced after intraoperative samples and tailored OPAT. Antibiotic schedule varied from six weeks to eight months. 12 (85.7%) patients remain under follow up. Mean follow is 20 months (RANGE 6months-3years10months) with no recurrence of infection or reoperation.

With appropriate patient selection, DAIR is safe and reproducible surgical option in PJI in hip and knee replacements, avoiding the implications of a one or two stage revision. Published Data in contemporary literature is predominantly from specialised centres. Our small series provides a perspective of early to mid term results of DAIR to DGH. Interestingly each procedure is categorised as a failed implant on the National Joint Register.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 45 - 45
1 Dec 2015
Finelli C Dell Aquila A Miki-Rosario N Fernandes H Dos Reis F Cohen M Abdalla R Da Silva C Murça M Nigro S Salles M
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Intramedullary nailing (IMN) has been frequently indicated to treat long bone open and closed fractures, but infection following internal fixation may have devastating consequences, with higher costs. Treatment of intramedullary nail-associated infections (IMNI) is challenging and based upon surgery and adequate antibiotic administration, which requires the correct identification of causative microorganisms. However, there have been difficulties for the microbial diagnosis of IMNI, as the peri-prosthetic tissue cultures may show no microbial growth, particularly in patients with previous use of antibiotics. Sonication have shown higher sensitivity and specificity for microbial identification on a variety of orthopedic implant-associated infections. Aim: To compare clinical and microbiological results and sensitivity for the pathogen identification obtained by conventional peri-implant tissue culture samples with culture of samples obtained by sonication of explanted IMN implants, among patients presenting IMNI of long bones.

Methods: Longitudinal prospective cohort study performed at a tertiary public hospital, ongoing since August 2011. We analyzed all patients with indication for IMN implant removal, and orthopedic-implant associated infections was defined according to previous publications addressing osteosynthesis-associated infections (Yano 2014). Minimal of 2 samples from the peri-implant tissue were taken and sent under sterile conditions to the laboratory for culture. Statistical analysis was performed McNemar's test for related proportions.

Results: We included 26 patients presenting clinical signs of IMNI, of which tissue and sonication cultures were performed for 26 (100%) and 20 (77%) patients, respectively. Among them, 88% were male, with mean age was 35.9 years (range, 19–59 yo). Causes of trauma were mainly motorcycle crashes accounting 54% of accidents; tibia and fibula were affected in 65% and 27%, respectively. Gustilo open fracture classification was grade II (35%) and IIIA (35%). First stage management with external fixation for fracture stabilization was performed in 75% of trauma patients. Sensitivity of peri-prosthetic tissue culture and sonication was 80.7% (21/26), and 95% (19/20) (p< 0.05), respectively. Only one infected patient presented negative tissue and fluid cultures. Gram-positive cocci were isolated in 75% and 79% in tissue and sonication fluid cultures, respectively. Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus sp., were isolated from tissue and sonication culture in 43.5% and 36.3%, 8.7% and 22.7%, 13% and 13.7%, respectively. Polymicrobial infection was diagnosed in 3.8% (1/26) and 15.8% (3/19), patients by tissue and sonication fluid cultures (p< 0,01), respectively.

Conclusion: Sonication of retrieved infected intramedullary nails has the potential for improving the microbiological diagnosis of IMNI.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 2 | Pages 222 - 226
1 Feb 2012
Rodrigues-Pinto R Freitas D Costa LD Sousa R Trigueiros M Lemos R Silva C Oliveira A

Radial osteotomy is currently advocated for patients with Lichtman’s stages II and IIIA of Kienböck’s disease; its place in the treatment of patients with stage IIIB disease remains controversial. The purpose of this study was to evaluate the medium-term results of this procedure and to compare the outcome in patients with stage IIIB disease and those with earlier stages (II and IIIA). A total of 18 patients (18 osteotomies) were evaluated both clinically and radiologically at a mean follow-up of 10.3 years (4 to 18). Range of movement, grip strength and pain improved significantly in all patients; the functional score (Nakamura Scoring System (NSSK)) was high and self-reported disability (Disabilities of Arm, Shoulder and Hand questionnaire) was low at the final follow-up in all patients evaluated. Patients with stage IIIB disease, however, had a significantly lower grip strength, lower NSSK scores and higher disability than those in less advanced stages. Radiological progression of the disease was not noted in either group, despite the stage. Radial osteotomy seems effective in halting the progression of disease and improving symptoms in stages II, IIIA and IIIB. Patients with less advanced disease should be expected to have better clinical results.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 162 - 162
1 May 2011
Sousa R Pereira A Massada M Freitas D Claro R Ramos J Trigueiros M Lemos R Silva C
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Background: Braquial plexus injuries are a major indication for shoulder arthrodesis today. Numerous investigations have addressed the optimal position of the extremity for shoulder arthrodesis, and there are still numerous opinions on the ideal position. The present consensus appears to favor less abduction and forward flexion and more internal rotation.

Purposes: Our main goal is to determine the most favorable position for arthrodesis regarding upper limb function and prevalence of periscapular pain. Secondarily we describe the fusion and complications rate as well as patient satisfaction.

Materials and Methods: Between 1997 and 2008 the authors performed a total of 19 shoulder arthrodesis using a pelvic reconstruction plate in patients with braquial plexus injuries. Six were lost to follow-up leaving a total of 11 men and two women with a mean age of 46 years available for review. At a mean follow-up of 101 months [13–149] patients were evaluated clinically using predetermined functional parameters (hand-to-mouth, brachiothoracic grip, etc) and the visual analog pain scale. DASH score and radiological studies were also performed. Three patients that presented no active elbow flexion were excluded of the functional results analysis.

Results: The mean fusion position found was 20° abduction, 32° forward flexion and 44° internal rotation. Abduction ≥ 25° relates to better function as judged by a better hand-to-mouth and brachiothoracic grip ratio as well as a better DASH score (38.8 vs. 45.4) but is also unfortunately related to higher periscapular pain prevalence (VAS pain 3.75 vs. 1.38). Forward flexion ≤ 30° also relates to slightly higher periscapular pain prevalence (VAS pain 2.7 vs. 1.7) and a better DASH score (39.5 vs. 47.7). Exaggerated internal rotation seems to have a negative influence on the functional outcome. Although relating to a surprisingly better DASH score (39.7 vs. 44.9), none of the three patients presenting with internal rotation over 45° was able to reach the mouth with his/her hand. Fusion was obtained in 12 patients. Major complications included one pseudarthrosis, one malpositioning of the extremity that forced a revision surgery to increase internal rotation and one humeral shaft fracture treated conservatively. All but one patient (including those with no active elbow flexion) were satisfied/very satisfied with the final outcome.

Discussion: Our results suggest abduction around 25° and forward flexion of no more than 30° are needed. Higher abduction and lower forward flexion values although relating to better function do so at the expense of more periscapular pain. We agree with the present trend towards increasing internal rotation but found that it should not exceed 45°.


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_II | Pages 164 - 164
1 May 2011
Pinto RR Trigueiros M Lemos R Silva C
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Introduction: Long-term results of radial osteotomy for Kienbock’s disease seldom are seen in the literature. The purpose of this study was to evaluate its outcome.

Material: Fifteen patients submitted to radial osteotomy were followed by a mean period of 9,5 years. Mean age at the time of surgery was 32,1 years. On the basis of the Lichtman classification, one patient had Stage II, eight had Stage IIIA and six had Stage IIIB disease.

Methods: Patients were evaluated clinically for pain, grip and range of motion (ROM); radiologically, according to carpal height ratio, Stahl’s index (lunate colapse), and for sclerotic, cystic and degenerative carpal changes. These data were classified according to the Nakamura Scoring System for Kienbock (NSSK).

Results: Ten patients are asymptomatic and five have mild pain. ROM improved significantly by 20,8°. When compared with the contralateral wrist, mean range of motion was 78% in flexion and 76% in extension and mean grip strength was 82,3%. Carpal height ratio and Stahl’s index improved, as shown by a mean NSSK of 24,3 (ten Excellent and five Good results). There was no progression to wrist arthritis.

Discussion: Pain, ROM and grip strength improved significantly after surgery. Despite the mild radiologic changes, there seems to have been an improvement in inner structure of the ischemic lunate.

Conclusions: These results show that Radial Osteotomy is an effective procedure in improving clinical and functional scores, and in preventing wrist arthritis.


Orthopaedic Proceedings
Vol. 92-B, Issue SUPP_IV | Pages 581 - 581
1 Oct 2010
Sousa JM Claro R Massada M Oliveira F Pereira A Silva C Silva L Trigueiros M Vilaça A
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Aims: A previous study demonstrated that negative pressure wound therapy (NPWT) increases tissue pressure. This conflicts with the understanding that these dressings increase perfusion. This randomised case control study investigates the effects that circumferential NPWT has on perfusion in humans and how different suction pressures influence this.

Methods: Ten healthy volunteers were recruited into the study and sequentially randomised to receive suction pressures of either −400 mmHg or −125 mmHg. With both hands placed in circumferential NPWT dressings, suction was only applied to one hand. Perfusion of both hands was then analysed simultaneously using radioisotope perfusion imaging. After allowing one week for complete excretion and decay of the isotope, an identical experiment was done on the same volunteers’, this time using the contralateral hand as the test hand. A total of 20 scans were carried out. Data were analysed using the Wilcoxon and Mann-Whitney tests.

Results: In the hands that received suction pressures of −400 mmHg, there was a highly significant mean reduction in perfusion of 40% (SD 11.5%, p< 0.0005). In the hands that received suction pressures of −125 mmHg there was also a highly significant mean reduction in perfusion (mean 17%, SD 8.9%, p< 0.0005). The reduction in perfusion of the group undergoing NPWT at −400 mmHg was significantly greater than the group undergoing NPWT at −125 mmHg (p< 0.015).

Conclusion: Tissue perfusion beneath circumferential NPWT dressings is significantly reduced when suction is applied, regardless of whether suction pressures of −125 mmHg or −400 mmHg are utilised. There is a significantly greater reduction in perfusion at suction pressures of −400 mmHg, compared to −125 mmHg. This implies that circumferential NPWT should be used with extreme caution, if at all, on tissues with compromised perfusion. This finding represents a paradigm shift in our understanding of the mechanism of action of NPWT.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 14 - 14
1 Mar 2006
Silva C
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Congenital Hand Deformities are probably the most frequent cause of non-traumatic complaint in consultations on paediatric hand surgery.

The incidence of occurrence is about 1 in 500 live births. Some of these abnormalities are minor and do not interfere with function. Many, however, have a significant functional and/or cosmetic deformity.

Only a few congenital malformations have a regular single gene mode of transmission, most have an irregular and unpredictable pattern of inheritance; sometimes occurs as part of a malformation syndrome or skeletal dysplasia, or in a sporadic way.

In fact, the cause for 40 to 50% of these anomalies is “unknown”.

Themes like handling the patient and parents and the psychological effects of the anomaly, the general principles of treatment, timing of surgery and the principles of reconstructive surgery are discussed.

The classification proposed by A.B. Swanson and revised with the assistance of the Congenital Anomalies Committee of the International Federation of Societies fo Surgery of the Hand will be used to propose the general guides of treatment.

The most common anomalies will be approached in more detail and the option of treatment is discussed in base of experience of the author.


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_I | Pages 4 - 4
1 Mar 2005
Nobbs E Reid R De Silva C Porter DE
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Introduction: The aims of the study were to analyse the presenting features of chondroasarcoma for prognostic significance, to observe the effects of grade and surgical management on local recurrence, metastasis and survival: and to assess the significance of delays to consultation and treatment.

Methods: From Scottish Bone Tumour Registry Records, 24 proximal humeral chondrosarcomas were treated between 1937 and 2002 in several hospitals in Scotland. Clinical records were available for all patients. Only 4 patients were eventually lost to follow-up. Age at presentation ranged for 16 to 79 (median 56) and male to female ration was 2:1. Patients were followed up for a range of 5 months to 24 years (median 6.5 years). Tumour histology was systematically reviewed: 5 (22%) were grade 1, 12 (52%) were grade 2, and 6 (26%) were grade 3. Dedifferentiated tumours were considered as grade 3.

Results: Pain was almost invariable (23/24), but its severity increased with grade. In the absence of pathological fracture (fracture in 4 Patients), swelling was significantly associated with increasing grade (X2+8.56, p+0.0139), as was symptom progression (X2=7.52, p=0.0232). Delay in diagnosis was calculated separately as ‘patient delay’ (range 0–69 months) and ‘doctor delay’ (range 0–132 months). No improvement in diagnostic delay was noted in this time period (1937–2002)

All cases were biopsied. 37% of these were excisional biopsies, 29% were incisional biopsies and 17% were needle biopsies. 21 patients (88%) received definitive surgery. Of these 5 had forequarter amputations (24%), 11 cases were excised marginally (52%), and 5 cases curetted (24%). Surgical choice was highly dependent on grade (X2=4.9256, p=0.005). In all cases the intent was curative.

2 patients had metastasis disease at diagnosis, and 5 developed metastases after definitive surgery. 4 patients had local recurrence (all had undergone wide local excision). All patients with grade 1 tumours remained disease free. Cumulative survival at 5 years was 57% and at 10 years 42%. Patient age did not affect survival. 5 year survival in grade 1, 2 and 3 tumours was 100%, 83% and 20% respectively. 4 of 5 patients undergoing amputation developed metastases and survival was significantly worse in the amputation group. Local recurrence in the wide local excision group did not diminish prospects for survival.

Discussion: Swelling predicts aggressive disease; as found in studies in childhood sarcomas. Progressive symptoms and serve pain are additional features indicative of high histological grade. In contract to improvements noted in several other studies, patient delay is highly variable and has not been demonstrably reduced over time.

Curettage was chosen for most grade 1 and some grade 2 tumours. Although maintenance of function is far better, our study provides no evidence that curettage results in increased local recurrence rates. Indeed, local recurrence in the wide local excision group did not depress survival figures. Because of early death in the amputation group, we would recommend avoidance of amputation in favour of wide local excision in almost all cases if possible. Age alone should not be a factor in determining surgical treatment.