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BACKGROUND: There is no clear consensus on whether total elbow arthroplasty (TEA) or hemiarthroplasty (HA) is superior for treating distal humerus fractures in the elderly. This study analysed the functional outcomes and re-operation rates following TEA and HA for intra-articular distal humerus fractures in patients aged ≥65 years. METHODS: 19 patients (TEA = 12, HA = 7) treated between 2016 and 2022 were retrospectively reviewed. Mean age was 73 years and mean follow-up was 46 months. Functional outcomes and quality of life were assessed using the Mayo Elbow Performance Score (MEPS), Quick-DASH (Q-DASH), Oxford Elbow Score (OES), SF-12 Physical Component Score (PCS) and Mental Component Score (MCS), and EQ-5D. Complications requiring re-operation were recorded. RESULTS: HA showed superior outcomes in MEPS (93.6 vs 75.0, p = 0.0339), Q-DASH (13.3 vs 31.3, p = 0.0182), OES (41.7 vs 33.2, p = 0.0346), SF-12 PCS (55.5 vs 36.9, p = 0.0008) and EQ-5D (83 vs 67, p = 0.0023). One HA patient required revision to TEA for prosthetic joint infection. One TEA patient required revision for a periprosthetic ulna fracture. CONCLUSION: HA provides better functional outcomes compared to TEA in the treatment of distal humerus fractures in the elderly. Data is limited by selection bias and low patient numbers with a multicentre randomised controlled trial warranted.
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BACKGROUND: Patients with osteonecrosis of the femoral head secondary to DDH frequently require total hip arthroplasty (THA), but it is not well understood which factors necessitate this requirement. We determined the incidence of THA in patients who have osteonecrosis secondary to DDH and factors associated with need for THA. METHODS: We included patients who received closed or open reductions between 1995 and 2005 with subsequent development of osteonecrosis. We determined osteonecrosis according to Bucholz and Ogden; osteoarthritis severity (Kellgren-Lawrence), subluxation (Shenton's line); neck-shaft angle; and acetabular dysplasia (centre-edge and Sharp angles). We also recorded the number of operations of the hip in childhood and reviewed case notes of patients who received THA to describe clinical findings prior to THA. We assessed the association between radiographic variables and the need for THA using univariate logistic regression. RESULTS: Of 140 patients (169 hips), 22 patients received 24 THA (14%) at a mean age of 21.3 ± 3.7 years. Associated with the need for THA were grade III osteonecrosis (OR 4.25; 95% CI 1.70-10.77; p = 0.0019), grade IV osteoarthritis (21.8; 7.55-68.11; p < 0.0001) and subluxation (8.22; 2.91-29.53; p = 0.0003). All patients who required THA reported at least 2 of: severe pain including at night, stiffness, and reduced mobility. Acetabular dysplasia and number of previous operations were not associated with the need for THA. CONCLUSIONS: We identified a 14% incidence of THA by age 34 years in patients with osteonecrosis secondary to DDH. Grade III osteonecrosis (global involvement femoral head and neck) was strongly associated with THA, emphasising the importance to avoid osteonecrosis when treating DDH.
Subject(s)
Arthroplasty, Replacement, Hip , Developmental Dysplasia of the Hip , Femur Head Necrosis , Humans , Arthroplasty, Replacement, Hip/adverse effects , Female , Male , Femur Head Necrosis/etiology , Femur Head Necrosis/epidemiology , Femur Head Necrosis/diagnostic imaging , Developmental Dysplasia of the Hip/surgery , Developmental Dysplasia of the Hip/diagnostic imaging , Developmental Dysplasia of the Hip/epidemiology , Adult , Young Adult , Adolescent , Retrospective Studies , Radiography , Incidence , Hip Dislocation, Congenital/surgery , Hip Dislocation, Congenital/diagnostic imaging , Hip Dislocation, Congenital/complications , Osteoarthritis, Hip/surgery , Osteoarthritis, Hip/diagnostic imaging , Osteoarthritis, Hip/epidemiology , Osteoarthritis, Hip/etiologyABSTRACT
BACKGROUND: Cutibacterium acnes (C acnes) is a commensal skin bacterium, primarily found in sebaceous glands and hair follicles, with a high prevalence in the shoulder region. It is the most common pathogenic organism in prosthetic joint infections after shoulder arthroplasty. Because of its low virulence, its diagnosis remains difficult. PURPOSE: To evaluate the relative effects of topical preparations in reducing C acnes in shoulder surgery. STUDY DESIGN: Meta-analysis; Level of evidence, 1. METHODS: We searched the MEDLINE, Embase, PsychINFO, and Cochrane Library databases in March 2022. Randomized controlled trials (RCTs) comparing any form of topical preparation in arthroscopic or open shoulder surgery were included. The primary outcome was a reduction in the number of positive C acnes cultures. Secondary outcomes were adverse events related to the application of topical preparations. We performed a network meta-analysis to facilitate simultaneous comparisons between multiple preparations across studies. We calculated differences between preparations using odds ratios and their 95% CIs. The risk of bias was assessed using the Cochrane risk-of-bias tool. RESULTS: The search yielded 17 RCTs (1350 patients), of which 9 were suitable for the network meta-analysis (775 patients). Overall, 2 RCTs were deemed as having a low risk of bias, and 15 raised "some concerns" of bias. Preparations included benzoyl peroxide (BPO), BPO combined with clindamycin, chlorhexidine gluconate, hydrogen peroxide, povidone-iodine, and water with soap. Only BPO resulted in significantly lower odds of a positive C acnes culture compared with placebo or soap and water (odds ratio, 0.12 [95% CI, 0.04-0.36]). There was no statistically significant difference with all other topical preparations. The only adverse events were skin irritation from BPO and chlorhexidine gluconate in a small number of reported cases. CONCLUSION: BPO was the most effective topical agent in reducing the prevalence of C acnes in shoulder surgery. These results were limited by a combination of indirect and direct data. Future studies should focus on establishing the optimal frequency and duration of preoperative BPO to further reduce the burden of C acnes. REGISTRATION: CRD42022310312 (PROSPERO).
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BACKGROUND: Tranexamic acid (TXA), a synthetic antifibrinolytic drug, effectively reduces blood loss by inhibiting plasmin-induced fibrin breakdown. This is the first study in the United Kingdom to investigate the effectiveness of TXA in the surgical management of isolated spine trauma. AIM: To assess the safety of TXA in isolated spine trauma. The primary and secondary outcomes are to assess the rate of thromboembolic events and to evaluate blood loss and the incidence of blood transfusion, respectively. METHODS: This prospective observational study included patients aged ≥ 17 years with isolated spine trauma requiring surgical intervention over a 6-month period at two major trauma centers in the United Kingdom. RESULTS: We identified 67 patients: 26 (39%) and 41 (61%) received and did not receive TXA, respectively. Both groups were matched in terms of age, gender, American Society of Anesthesiologists grade, and mechanism of injury. A higher proportion of patients who received TXA had a subaxial cervical spine injury classification or thoracolumbar injury classification score > 4 (74% vs 56%). All patients in the TXA group underwent an open approach with a mean of 5 spinal levels involved and an average operative time of 203 min, compared with 24 patients (58%) in the non-TXA group who underwent an open approach with an average of 3 spinal levels involved and a mean operative time of 159 min. Among patients who received TXA, blood loss was < 150 and 150-300 mL in 8 (31%) and 15 (58%) patients, respectively. There were no cases of thromboembolic events in any patient who received TXA. CONCLUSION: Our study demonstrated that TXA is safe for isolated spine trauma. It is challenging to determine whether TXA effectively reduces blood loss because most surgeons prefer TXA for open or multilevel cases. Further, larger studies are necessary to explore the rate, dosage, and mode of administration of TXA.
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BACKGROUND: To date, there are no systematic reviews on the utility of surgical management for plantar fasciitis to guide best practice. This review aimed to evaluate the operative options for plantar fasciitis and their effectiveness. METHODS: A systematic review and network meta-analysis were carried out in accordance with PRISMA guidelines. A search strategy was conducted on the MEDLINE, EMBASE, and Cochrane databases. Quality was assessed using the ROBINS-I tool. RESULTS: 17 studies involving 865 patients were included. Surgical options considered were open and endoscopic plantar fasciotomy, gastrocnemius release, radiofrequency microtenotomy and dry needling. All interventions resulted in improvement in VAS and AOFAS scores. No major complications were seen from any treatment modality. CONCLUSIONS: Surgical interventions are effective in providing short- to medium-term symptomatic relief for plantar fasciitis refractory to non-operative management. Current evidence is equivocal regarding treatment choice. Further large randomised studies are required to establish long-term outcomes and a management algorithm. LEVEL OF EVIDENCE: Level III.
Subject(s)
Fasciitis, Plantar , Humans , Fasciitis, Plantar/surgery , Network Meta-Analysis , Fasciotomy , Pain Measurement , Muscle, Skeletal , Treatment OutcomeABSTRACT
Introduction: Propionibacterium acnes is a gram-positive anaerobe that is found on the dermis and epidermis of the shoulder and is the most commonly identifiable cause of periprosthetic shoulder joint infection. Various topical strategies have been investigated to reduce the prevalence of P acnes, with several demonstrating efficacy in reducing the positive culture. The aim of this systematic review and meta-analysis is to review the literature to assess the effectiveness of topical preparations in reducing the prevalence of P acnes in shoulder surgery. Methods: The study protocol was designed and registered prospectively on PROSPERO (International prospective register for systematic reviews). Databases used for the literature search will include MEDLINE, EMBASE, PsycINFO, and The Cochrane Library. Randomised controlled trials (RCTs) evaluating the use of any topical preparation against placebo, in all types of shoulder surgery, will be included. Our primary outcome is the number of colony forming units of P acnes. Secondary outcomes will include adverse events such as skin irritation, wound dehiscence, and the incidence of revision surgery due to infection. The Cochrane Risk of Bias Tool 2.0 and Jadad score will be used to assess the quality of methodology of the studies. Statistical analysis will be used to assess inconsistency and bias across included studies. Comparable outcome data will be pooled and analysed quantitatively or qualitatively as appropriate. Ethics and dissemination: No ethical clearances required for this study. This systematic review and meta-analysis will be published in a peer-reviewed journal. Highlights: Various topical strategies have been investigated to reduce the prevalence of P acnes, the most common identifiable cause of periprosthetic shoulder joint infection, with several demonstrating efficacy in reducing the positive culture.This systematic review and meta-analysis evaluates the effectiveness of topical preparations in reducing the prevalence of P acnes in shoulder surgery.Our primary outcome is the number of colony forming units of P acnes. Registration: PROSPERO 2022 CRD42022310312.
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(1) Background: Management of metastatic periacetabular lesions remains a challenging area of orthopaedics. This study aims to evaluate and summarize the currently available reconstructive modalities, including their indications and outcomes. (2) Methods: A scoping review was carried out in accordance with PRISMA guidelines. Medline, EMBASE, and Cochrane were searched for relevant articles. (3) Results: A total of 18 papers met inclusion criteria encompassing 875 patients. The most common primary malignancy was breast (n = 230, 26.3%). Reconstruction modalities used were total hip arthroplasty (n = 432, 49.1%), the Harrington procedure (n = 374, 42.5%), modular hemipelvic endoprotheses (n = 63, 7.2%) and a reverse ice-cream cone prosthesis (n = 11, 1.25%). (4) Conclusions: Advances in implant design including use of dual mobility or flanged cups, tantalum implants, and modular hemipelvic endoprostheses allow for larger acetabular defects to be addressed with improved patient outcomes. This armamentarium of reconstruction options allows for tailoring of the procedure performed depending on patient factors and extent of periacetabular disease.
Subject(s)
Arthroplasty, Replacement, Hip , Bone Neoplasms , Hip Prosthesis , Acetabulum/pathology , Acetabulum/surgery , Arthroplasty, Replacement, Hip/methods , Bone Neoplasms/surgery , HumansABSTRACT
BACKGROUND: Paediatric traumatic elbow dislocation occurs in 6 per 100,000 children per year and if not treated promptly can result in a poor outcome. Despite this, the long-term clinical and functional outcome of these injuries has not been well described using modern patient-reported outcome tools. The aim of our study was present the outcome of these injuries in the long term. METHODS: Twenty children with an acute traumatic elbow dislocation who presented between February 2007 to February 2016 were included in our study. Patient demographics, management and complications were recorded from the clinical notes. Ten children had associated fractures and were managed surgically, while the remaining were managed with closed reduction and immobilisation. Functional outcomes were assessed with Kim's elbow performance score. RESULTS: The mean age was 12 years (7 -15) and follow-up was 8 years (4 - 13). There was one (5%) re-dislocation requiring surgery and one (5%) ulna nerve neurapraxia that resolved within one month. The average Kim's scores were 87.5 (65 - 100) and 77.5 (60 - 100) in the closed reduction and open reduction groups, respectively (P=0.08). 80% (16/20) reported good or excellent outcome with a Kim's score of greater than 75 points with no cases of poor functional outcome reported in our series. CONCLUSIONS: Traumatic elbow dislocations in children, with or without associated fracture, have a good long-term functional outcome with appropriate early management.
Subject(s)
Elbow Injuries , Elbow Joint , Fractures, Bone , Joint Dislocations , Child , Elbow , Elbow Joint/diagnostic imaging , Elbow Joint/surgery , Humans , Joint Dislocations/diagnostic imaging , Joint Dislocations/surgery , Range of Motion, Articular , Retrospective Studies , Treatment OutcomeABSTRACT
Introduction: Acute acromioclavicular joint separation is a common injury to the shoulder. Various surgical reconstruction methods exist when operative management is required, but the optimal procedure is not known. The aim of this systematic review and meta-analysis is to review the literature to assess the clinical effectiveness of various surgical reconstruction modalities used for acute ACJ separation. Methods: The study protocol was designed and registered prospectively on PROSPERO (International prospective register for systematic reviews). Literature search will include MEDLINE, EMBASE, PsycINFO, and The Cochrane Library electronic databases. Randomised controlled trials (RCTs) evaluating surgical procedures for acute acromioclavicular joint (ACJ) separation will be included. Our primary outcome is any functional patient-reported outcome measure related to the shoulder. Secondary outcomes may include radiological measurements, objective measurements of strength testing, range of motion, other patient-reported outcome measures not specific to the shoulder such as the Visual-Analog Scale (VAS) for pain, timelines for return to sport or work, and rate of complications. Risk of bias will be assessed within each study using The Cochrane Risk of Bias Tool 2.0 and the Jadad score. Inconsistency and bias across included studies will be assessed statistically. Comparable outcome data will be pooled and analysed quantitatively or qualitatively as appropriate. Ethics and dissemination: This study did not require ethical clearance. We plan to publish this systematic review and meta-analysis in a peer-reviewed journal and present the results at various national and international conferences. Highlights: There is currently variation in surgical synthetic ligament reconstruction techniques for acute acromioclavicular separation, with no clear consensus established.This systematic review evaluates the clinical effectiveness of various surgical reconstruction modalities used for acute ACJ separation.Our primary outcome is any functional patient-reported outcome measure related to the shoulder.
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BACKGROUND: Talus fractures are devastating injuries in both adults and children. Well recognised complications such as avascular necrosis (AVN), post-traumatic arthritis and non-union contribute to patient morbidity. This systematic review aimed to assess the literature on these injuries in children and their associated incidence, classification, management and outcome. METHODS: A systematic review of Embase and Medline databases was carried out in accordance with PRISMA guidelines. Inclusion criteria were clinically orientated studies looking at talus fractures in paediatric patients (less than 18 years old). Exclusion criteria were conference abstracts, opinion-based reports, articles not published in English and articles published prior to 1980. Data extracted included patient demographics, fracture classification, management and outcomes. RESULTS: 31 studies were included encompassing 143 patients and 167 fractures with a mean age of 11.9 years (1.2-18). The majority of fractures (43.7%, n = 73) were of the talar neck. 70.6% (n = 101) were managed operatively. The overall rate of AVN was 15.4% (n = 22), with a 96.5% union rate. Observed rates of AVN were 5.7% in Hawkin's 1, 11.8% in Hawkin's 2, 53.3% in Hawkin's 3 and 0 in Hawkin's 4 injuries. All cases of non-union occurred in children over 12 years, and seven children required arthrodesis (1x pantalar, 1x subtalar and 5x subtalar and tibiotalar) with a mean age of 14.4 years (9-17). CONCLUSIONS: Talus fractures are rare but potentially devastating injuries in children. This systematic review has shown comparable rates of AVN in children to their adult counterparts, with higher rates of non-union and arthrodesis in adolescent patients. A lower threshold for operative intervention to achieve anatomical reduction in these patients should be considered.
Subject(s)
Ankle Fractures , Fractures, Bone , Osteonecrosis , Talus , Adolescent , Adult , Ankle Fractures/complications , Ankle Fractures/diagnostic imaging , Ankle Fractures/surgery , Arthrodesis/adverse effects , Child , Fracture Fixation, Internal/adverse effects , Fractures, Bone/surgery , Humans , Osteonecrosis/etiology , Talus/surgeryABSTRACT
PURPOSE: Severe upper limb injuries can result in devastating consequences to functional and psychological well-being. Primary objectives of this review were to evaluate indications for amputation versus limb salvage in upper limb major trauma and whether any existing scoring systems can aid in decision-making. Secondary objectives were to assess the functional and psychological outcomes from amputation versus limb salvage. METHODS: A systematic review was carried out in accordance with PRISMA guidelines. A search strategy was conducted on the MEDLINE, EMBASE, and Cochrane databases. Quality was assessed using the ROBINS-I tool. The review protocol was registered in PROSPERO. RESULTS: A total of 15 studies met inclusion criteria, encompassing 6113 patients. 141 underwent primary amputation and 5972 limb salvage. General indications for amputation included at least two of the following: uncontrollable haemodynamic instability; extensive and concurrent soft tissue, bone, vascular and/or nerve injuries; prolonged limb ischaemia; and blunt arterial trauma or crush injury. The Mangled Extremity Severity Score alone does not accurately predict need for amputation, however, the Mangled Extremity Syndrome Index may be a more precise tool. Comparable patient-reported functional and psychological outcomes are seen between the two treatment modalities. CONCLUSIONS: Decision regarding amputation versus limb salvage of the upper limb is multifactorial. Current scoring systems are predominantly based on lower limb trauma, with lack of robust evidence to guide management of the upper extremity. Further high-quality studies are required to validate scoring systems which may aid in decision-making and provide further information on the outcomes from the two treatment options.
Subject(s)
Leg Injuries , Limb Salvage , Amputation, Surgical/methods , Humans , Injury Severity Score , Leg Injuries/surgery , Limb Salvage/methods , Retrospective Studies , Treatment Outcome , Upper Extremity/surgeryABSTRACT
BACKGROUND: The TFNA (Trochanteric Fixation Nail Advanced) Proximal Femoral Nailing System (DePuy Synthes) is frequently used for intramedullary fixation of proximal femoral fractures. The aim of this study was to evaluate all TFNA implant fractures at a UK trauma unit to ascertain any patient or surgical factors associated with implant failure. METHODS: A retrospective study was carried out identifying all patients that sustained a TFNA implant fracture over a five-year period. Data was collected on demographic information, ASA, co-morbidities, mechanism of injury, fracture pattern according to the AO/OTA classification, procedure details and time to failure. Radiographs were assessed by two independent reviewers to identify tip-apex distance (TAD), calcar TAD, reduction quality and union status at time of implant failure. RESULTS: Six cases were identified, all with implant breakage at the aperture for the proximal screw. All femoral fractures were intertrochanteric reverse obliquity type (OA/OTA 31A3). Two were traumatic fragility fractures and the remainder atraumatic. Mean time from index surgery to revision was 441 days (104-963). Mean TAD was 20.5 mm (15-24) and mean calcar TAD 24 mm (18-32). All six cases displayed radiographic non-union at the time of implant fracture. CONCLUSION: Pathological fractures resulting in reverse obliquity type fracture patterns and subsequent non-union appear to be contributory factors to TFNA breakage at the proximal screw aperture. This may be further exacerbated by alterations to the nail design from previous generations. In these patients, close follow up with clinical and radiographic surveillance should be employed. Further biomechanical and clinical studies are required to compare this finding against other nail designs.
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BACKGROUND: Reconstruction of the hip for peri-acetabular oncological disease remains a challenge. The objective of this study was to summarize the evidence and identify techniques utilized for primary and metastatic tumors of the acetabulum and hemipelvis. METHODS: A systematic review of the published literature was carried out in accordance with PRISMA guidelines. MEDLINE, EMBASE and Cochrane databases identified relevant articles. Quality was assessed using the Newcastle-Ottawa Scale. The study was registered on PROSPERO. RESULTS: 53 papers were included, 16 were suitable for meta-analysis. 909 patients had primary and 1140 metastatic disease. 1094 patients underwent reconstruction with conventional total hip arthroplasty (with or without cup-cage or cement augmentation) or modifications of the Harrington procedure, collectively termed 'non-complex'. 928 patients underwent 'complex' reconstructions with either a modular hemipelvic, saddle, reverse snow-cone, custom-made or 3D-printed endoprosthesis. The most common complication was deep infection (11%) followed by dislocation (5%). Mean MSTS scores were 61.9% for 'non-complex' versus 63.2% for 'complex' reconstruction. Meta-analysis suggested increased mortality for primary (OR 3.14; 95% CI 1.15-8.54) and trends toward reduced mortality for metastatic disease (OR 0.93; 95% CI 0.26-3.29) following 'complex' versus 'non-complex' reconstruction. Reoperation rates were higher following 'complex' reconstruction for metastatic disease (OR 1.90; 95% CI 0.66-5.46) and similar for primary disease (OR 0.98; 95% CI 0.45-2.14). CONCLUSIONS: Peri-acetabular tumors are associated with high rates of morbidity and mortality. Decisions regarding implant selection are multi-factorial with recent increase in the use of custom-made and 3D-printing technologies. Multiple factors contribute to the oncological outcome and patient function. Further research is required in order to guide optimal practice.
Subject(s)
Acetabulum/surgery , Arthroplasty, Replacement, Hip/methods , Bone Neoplasms/surgery , Plastic Surgery Procedures/methods , Survivorship , Acetabulum/pathology , Bone Neoplasms/pathology , Humans , Treatment OutcomeABSTRACT
PURPOSE: This study assesses whether sterile surgical helmet systems (SSHS) provide surgeons with additional protection from aerosol pathogens alongside their traditional role protecting against splash. There has been debate on whether to use such systems in reopening elective orthopaedic surgery during the current COVID-19 pandemic environment. METHODS: Thirty-five participants were enrolled in a double-blinded randomised controlled study investigating efficacy of the Stryker Flyte Surgical Helmet (Stryker Corporation, Kalamazoo, MI, USA) as protection against respiratory droplets. Wearing the SSHS in a fit testing hood, subjects were randomised to nebulised saccharin solution or placebo. Twenty were allocated to the saccharin group with 15 to placebo. Positive sweet taste represented a failure of the test. Taste tests were performed with the helmet fan turned on and off. RESULTS: SSHS did not prevent saccharin taste (p < 0.0001). Within the saccharin cohort, 40% recorded a positive taste with the fan on and 100% with the fan off. There was a statistically significant difference in mean time-to-taste saccharin (p = 0.049) comparing fan on (123.5 s) vs. off (62.6 s). CONCLUSIONS: SSHS do not protect against aerosol particulate and therefore are not efficacious in protection against COVID-19. The fan system employed may even increase risk to the surgeon by drawing in particulates as well as delay recognition of intraoperative cues, such as exhaust from diathermy, that point to respirator mask leak.
Subject(s)
COVID-19 , Head Protective Devices , Humans , Orthopedic Procedures , SARS-CoV-2ABSTRACT
Interleukin-15 (IL-15) is a cytokine that has been shown to expand CD8 T cell and natural killer (NK) cell populations, and therefore has potential for potentiating adoptive immune cell therapy for cancer. Previously, IL-15 has been shown to induce proliferation of CD8 memory T cells through activation of telomerase. Here, we investigated whether telomerase is also activated during the IL-15 mediated proliferation of NK and NKT-like (CD56+CD3+) cells. We also examined the extent that each of the three signaling pathways known to be stimulated by IL-2/IL-15 (JAK-STAT, PI3K-AKT Ras-RAF/MAPK) were activated and involved in the telomerase expression in the three cell types NK, NKT, or CD8 T cells. To assess cell proliferation and doubling, peripheral blood mononuclear cells (PBMCs) or isolated NK, NKT-like or CD8 T cells were incubated with varying concentrations of IL-15 or IL-2 for 7 days. CD8 T, NK, and NKT cell expansion was determined by fluorophore-conjugated antibody staining and flow cytometry. Cell doubling was investigated using carboxyfluorescein-succinimidyl-ester (CFSE). Telomerase expression was investigated by staining cells with anti-telomerase reverse transcriptase (anti-TERT). Telomerase activity in CD56+ and CD8 T cells was also measured via Telomerase Repeat Amplification Protocol (TRAP). Analysis of cellular expansion, proliferation and TERT expression concluded that IL-15 increased cellular growth of NK, NKT, and CD8 T cells more effectively than IL-2 using low or high doses. IL-15, increased TERT expression in NK and NKT cells by up to 2.5 fold, the same increase seen in CD8 T cells. IL-2 had effects on TERT expression only at high doses (100-1000 ng/ml). Proteome profiling identified that IL-15 activated selected signaling proteins in the three pathways (JAK-STAT, PI3K-AKT, Ras-MAPK) known to mediate IL-2/IL-15 signaling, more strongly than IL-2. Evaluation by signaling pathway inhibitors revealed that JAK/STAT and PI3K/AKT pathways are important in IL-15's ability to upregulate TERT expression in NK and NKT cells, whereas all three pathways were involved in CD8 T cell TERT expression. In conclusion, this study shows that IL-15 potently stimulates TERT upregulation in NK and NKT cells in addition to CD8 T cells and is therefore a valuable tool for adoptive cell therapies.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Cell Proliferation , Gene Expression Regulation, Enzymologic/immunology , Interleukin-15/immunology , Killer Cells, Natural/immunology , Natural Killer T-Cells/immunology , Telomerase/immunology , Up-Regulation/immunology , HumansABSTRACT
BACKGROUND: Virtual reality (VR) simulation is a vital component of surgical training with demonstrated improvements in surgical quality and clinical outcome. AIMS: To validate the LAP Mentor (Simbionix™) laparoscopic appendicectomy (LA) VR simulator with inclusion of a novel tool, Cognitive Task Analysis (CTA). METHODS: Thirty-two novices and nine experienced surgeons performed two simulated LAs. An expert-consensus questionnaire guided face validity assessment. Content validity was assessed using CTA-derived questions encompassing eight operative steps and four decision points. Construct validity was evaluated using dexterity metrics, masked assessment of surgical quality using the OSATS global rating scale, and mental workload from two validated tools: the NASA-TLX and SMEQ. Ten novices performed eight further LAs for learning curve assessment. RESULTS: Face validity was demonstrated across all domains. Considering content validity, the essential technical and non-technical steps were evident. The experienced group performed the procedure quicker (median time 361 vs. 538 s, P = 0.0039) with fewer total movements (426 vs. 641, P < 0.0001) and shorter idle time (131 vs. 199 s, P = 0.0006). This correlated with higher OSATS scores (median 33.5 vs. 22.2, P < 0.0001) and lower mental demand (NASA-TLX: 9.0 vs. 13.75, P = 0.012; SMEQ: 60 vs. 80, P = 0.0025), indicating construct validity. Learning curve data showed statistically significant improvements after the 7th session for procedure time, total movements and idle time, which correlated with reduction in mental demand. CONCLUSIONS: The LAP Mentor demonstrates face, content and construct validity for LA; thus, it can be used as an effective tool in surgical training. Task repetition leads to achievement of expert benchmarks.