Regeneration of bone defects in elderly patients is limited due to the decreased function of bone forming cells and compromised tissue physiology. Previous studies suggested that the regenerative activity of stem cells from aged tissues can be enhanced by exposure to young systemic and tissue microenvironments. The aim of our project was to investigate whether extracellular matrix (ECM) engineered from human induced pluripotent stem cells (hiPSCs) can enhance the bone regeneration potential of aged human bone marrow stromal cells (hBMSCs). ECM was engineered from hiPSC-derived mesenchymal-like progenitors (hiPSC-MPs), as well as young (<30 years) and aged (>70 years) hBMSCs. ECM structure and composition were characterized before and after decellularization using immunofluorescence and biochemical assays. Three hBMSCs of different ages were cultured on engineered ECMs. Growth and differentiation responses were compared to tissue culture plastic, as well as to collagen and fibronectin coated plates. Decellularized ECMs contained collagens type I and IV, fibronectin, laminin and < 5% residual DNA, suggesting efficient cell elimination. Cultivation of young and aged hBMSCs on the hiPSC-ECM in osteogenic medium significantly increased hBMSC growth and markers of osteogenesis, including collagen deposition, alkaline phosphatase activity, bone sialoprotein expression and matrix mineralization compared to plastic controls and single protein substrates. In aged BMSCs, matrix mineralization was only detected in ECM cultures in osteogenic medium. Comparison of ECMs engineered from hiPSC-MPs and hBMSCs of different ages suggested similar structure, composition and potential to enhance osteogenic responses in aged BMSCs. Engineered ECM induced a higher osteogenic response compared to specific matrix components. Our studies suggest that aged BMSCs osteogenic activity can be enhanced by culture on engineered ECM. hiPSCs represent a scalable cell source, and tissue engineering strategies employing engineered ECM materials could potentially enhance bone regeneration in elderly patients

With an aging population and increase in total knee arthroplasty, periprosthetic distal femur fractures (PDFFs) have increased. The differences between these fractures and native distal femur fractures (NDFF) have not been comprehensively investigated. The purpose of this study was to compare the demographic, fracture, and treatment details of PDFFs compared to NDFFs. A retrospective study of patients ≥ 18 years old who underwent surgical treatment for either a NDFF or a PDFF from 2010 to 2020 at a level 1 trauma center was performed. Demographics, AO/OTA fracture classification, quality of reduction, fixation constructs, and unplanned revision reoperation were compared between PDFF patients and NDFF patients using t-test and Fisher's exact test. 209 patients were identified with 70 patients having a PDFF and 139 patients having a NDFF. Of note, 48% of NDFF had a concomitant fracture of the ipsilateral knee (14%) or tibial plateau (15%). The most common AO/OTA classification for PDFFs was 33A3.3 (71%). NDFFs had two main AO/OTA classifications of 33C2.2 (28%) or 33A3.2. (25%). When controlling for patient age, bone quality, fracture classification, and fixation, the PDFF group had increased revision reoperation rate compared to NDFF (P < 0.05). PDFFs tend to occur in elderly patients with low bone quality, have complete metaphyseal comminution, and be isolated; whereas, NDFF tend to occur in younger patients, have less metaphyseal comminution, and be associated with other fractures. When controlling for variables, PDFF are at increased risk of unplanned revision reoperation. Surgeons should be aware of these increased risks in PDFFs and future research should focus on these unique fracture characteristics to improve outcomes

Elective orthopaedic procedures, and particularly total hip arthroplasty (THA), in octogenarians and nonagenarians patients are burdened of several implications. Besides the comorbidities and the anesthesiological issues, legal and ethical implications are present. Some literature data show the clinical improvement of THA in elderly patient but the psychological aspects are not yet evaluated. Aim of this study is to evaluate the clinical aspects and the psychological impact in daily living in octogenarians and nonagenarians patients addressing THA. We conducted a retrospective evaluation of 81 THA in 81 patients of age more than 85 years with a minimum follow-up of 6 months. Clinical aspects were evaluated using the Hip disability and Osteoarthritis Outcome Score (HOOS). The psychological issues were evaluated with the Short Form 12 (SF-12) using both the Physical Component Summary (PCS) and the Mental Component Summary (MCS). From the starter cohort of 81 patients, 8 patients were died for causes unrelated to surgery, 13 were lost to follow-up, 1 patient was revised for periprosthetic fracture; 59 patients composed the final cohort. Mean HOOS rased from 18,07 ± 17,81 to 92,36 ± 5,74 with statistically significant distribution both in the global score than in all of the different subscales. The PCS raised from 26,81 ± 10,81 to 51,86 ± 4,45 and The MCS raised from 34,84 ± 10,81 to 56,70 ± 5,04, but none of them showed a statistically significant distribution. THA in octogenarians and nonagenarians patients could be a safe procedure with positive results for clinical and psychological aspects

Intra-Discal Vacuum Phenomenon (IDVP) represents an intradiscal nitrogen gas accumulation where a cavity opens in a supine position, lowering intra-discal pressure and generating a bubble. IDVP has been observed in up to 20% of elderly patients and reported in almost 50% of chronic LBP patients. With a highly accurate detection on CT, its significance lacks clarity and consideration within normative data. IDVP occurs with patterns of lumbar and/or lumbopelvic morphology and associated diagnoses. Over-60s population based sample of 2020 unrelated CT abdomen scans without acute spinal presentations, with sagittal reconstructions, inclusive of T12 to femoral heads, were analyzed for IDVP and pelvic incidence (PI). Subjects with diagnostic morphological associations of the lumbar spine, including previous fracture, autofusion, transitional vertebra and listhesis, were selected out and analyzed separately. Subjects were then equally grouped into low, medium and high PI. Prevalence of lumbar spine IDVP is 41.3%. 125 cases were excluded. 1603 subjects yielded 663 IDVP. This was increased in severity towards the lumbosacral junction (L1L2 9.4%, L2L3 10.9%, L3L4 13.7%, L4L5 19.9%, L5S1 28.5%) and those with low PI, while distribution was more even with high PI. 292 had positive diagnostic associations, which were more likely to occur at the level of isthmic spondylolisthesis, adjacent to a previous fracture or suprajacent to lumbosacral transitional vertebra (p<0.05). This study has identified normative values for prevalence and severity of IDVP in a normal aging population. Morphological patterns that influence the pattern of IVDP such as pelvic incidence and diagnostic associations provide novel insights to the function of the aging spine

C. Difficile infections in elderly patients with hip fractures is associated with high morbidity and mortality. Antibiotic regimens with penicillin and its derivatives is a leading cause. Antibiotic prophylactic preferences vary across different hospitals within NHS. We compared two antibiotic prophylactic regimens - Cefuroxime only prophylaxis and Teicoplanin with Gentamicin prophylaxis in fracture neck of femur surgery, and evaluated the incidence of C. Difficile diarrhea and Surgical Site Infection (SSI). To assess the Surgical Site Infection and C. Difficile infection rate associated with different regimens of antibiotics prophylaxis in fracture neck of femur surgery. Data was analyzed retrospectively. Neck of femur fracture patients treated surgically from 2009 in our unit were included. Age, gender, co morbidities, type of fracture, operation, ASA grade was collected. 1242 patients received Cefuroxime only prophylaxis between January 2009 and December 2012 (Group 1) and 486 patients received Teicoplanin with Gentamicin between October 2015 and March 2017 (Group 2). There were 353 males and 889 female patients in Group 1 and 138 males and 348 female patients in Group 2. The co morbidities in both groups were comparable. Incidence of C. Difficile diarrhea and Surgical Site Infection (SSI) was noted. Statistical analysis with chi square test was performed to determine the ‘p’ value. C. Diff diarrhea rate in Group 2 was 0.41 % as compared to 1.29 % in Group 1. The Surgical Site Infection (SSI) rate in Group 2 was 0.41 % as compared to 3.06 % in Group 1. The comparative results were statistically significant (p = 0.0009). Prophylactic antibiotic regimen of Teicoplanin with Gentamicin showed significant reduction in C. Difficile diarrhea & Surgical Site Infection in fracture neck of femur patients undergoing surgery

Introduction. The Achilles tendon is the thickest and strongest tendon in the human body. Even though the tendon is so strong, it is one of the most frequently injured tendons. Treatment of patients after rupture is planned conservatively and surgically. Conservative treatment is generally applied to elderly patients with sedentary lives. If the treatment is surgical, it can be planned as open surgery or percutaneous surgery. In our study with rabbits, we wrapped a membrane made of plga (polylactic-co-glycolic acid) nanotubes impregnated with type 1 collagen around the tendon in rabbits that underwent open Achilles tendon repair surgery. After surgery, biomechanical and histological tests were performed on the tendons. Method. In the study consisting of 24 rabbits, 2 groups were created by random distribution. In the study group, after the Achilles tendon rupture was created, a type 1 collagen-impregnated plga-based membrane was placed around the tendon after the repair of 1 modified Kesslerr suture. In the control group, after the Achilles tendon rupture was created, 1 modified Kessler suture and Tendon repair was performed with the application of 3 primary sutures. At the end of the 6th week of the study, the rabbits in 2 groups were randomly distributed and histological examination was performed. Additionally, biomechanical testing was performed. Bonar and Movın scoring were used in histological examinations. Result. As a result of biomechanical tests, it was seen that the resistance of the tendon against rupture was higher in the study group than in the control group. In addition, it was observed that the tendon rupture time was longer in the study group than in the control group. Histological examinations gave supportive results from biomechanical tests. Conclusion. We think that the use of collagen-impregnated plga-based nanotubes in the surgical treatment of Achilles tendon ruptures has a positive healing effect. Although we think that the return to normal life after surgery may be faster, we believe that more clinical studies are needed

Odontoid fracture of the second cervical vertebra (C2) is the most common spinal fracture type in elderly patients. However, very little is known about the biomechanical fracture mechanisms, but could play a role in fracture prevention and treatment. This study aimed to investigate the biomechanical competence and fracture characteristics of the odontoid process. A total of 42 human C2 specimens (14 female and 28 male, 71.5 ± 6.5 years) were scanned via quantitative computed tomography, divided in 6 groups (n = 7) and subjected to combined quasi-static loading at a rate of 0.1 mm/s until fracturing at inclinations of −15°, 0° and 15° in sagittal plane, and −50° and 0° in transverse plane. Bone mineral density (BMD), specimen height, fusion state of the ossification centers, stiffness, yield load, ultimate load, and fracture type according to Anderson and d'Alonzo were assessed. While the lowest values for stiffness, yield, and ultimate load were observed at load inclination of 15° in sagittal plane, no statistically significant differences could be observed among the six groups (p = 0.235, p = 0.646, and p = 0.505, respectively). Evaluating specimens with only clearly distinguishable fusion of the ossification centers (n = 26) reveled even less differences among the groups for all mechanical parameters. BMD was positively correlated with yield load (R² = 0.350, p < 0.001), and ultimate load (R² = 0.955, p < 0.001), but not with stiffness (p = 0.070). Type III was the most common fracture type (23.5%). These biomechanical outcomes indicate that load direction plays a subordinate role in traumatic fractures of the odontoid process in contrast to BMD which is a strong determinant of stiffness and strength. Thus, odontoid fractures appear to result from an interaction between load magnitude and bone quality

Fragility ankles fractures in the geriatric population are challenging to manage, due to fracture instability, soft tissue compromise, patient co-morbidities. Traditional management options include open reduction internal fixation, or conservative treatment, both of which are fraught with high complication rates. We aimed to present functional outcomes of elderly patients with fragility ankle fractures treated with tibiotalocalcaneal nails. 171 patients received a tibiotalocalcaneal nail over a six-year period, but only twenty met the inclusion criteria of being over sixty and having poor bone stock, verified by radiological evidence of osteopenia or history of fragility fractures. Primary outcome was mortality risk from co-morbidities, according to the Charlson co-morbidity index (CCI), and patients’ post-operative mobility status compared to pre-operative mobility. Secondary outcomes include intra-operative and post-operative complications, six-month mortality rate, time to mobilisation and union. The mean age was 77.82 years old, five of whom are type 2 diabetics. The average CCI was 5.05. Thirteen patients returned to their pre-operative mobility state. Patients with low CCI are more likely to return to pre-operative mobility status (p=0.16; OR=4.00). Average time to bone union and mobilisation were 92.5 days and 7.63 days, respectively. Mean post-operative AOFAS ankle-hindfoot and Olerud-Molander scores were 53.0 (range 17-88) and 50.9 (range 20-85), respectively. There were four cases of broken distal locking screws, and four cases of superficial infection. Patients with high CCI were more likely to acquire superficial infections (p=0.264, OR=3.857). There were no deep infections, periprosthetic fractures, nail breakages, non-unions. TTC nailing is an effective treatment methodology for low-demand geriatric patients with fragility ankle fractures. This technique leads to low complication rates and early mobilisation. It is not a life-changing procedure, with many able to return to their pre-operative mobility status, which is important for preventing the loss of socioeconomic independence

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)

Intraoperative fractures although rare are one of the complications known to occur while performing a total hip arthroplasty (THA). However, due to lower incidence rates there is currently a gap in this area of literature that systematically reviews this important issue of complications associated with THA. Method: We looked into Electronic databases including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), the archives of meetings of orthopaedic associations and the bibliographies of included articles and asked experts to identify prospective studies, published in any language that evaluated intra-operative fractures occurring during total hip arthroplasty from the year 1950-2020. The screening, data extraction and quality assessment were carried out by two researchers and if there was any discrepancy, a third reviewer was involved. Fourteen studies were identified. The reported range of occurrence of fracture while performing hip replacement surgery was found to be 0.4-7.6%. Major risk factors identified were surgical approaches, Elderly age, less Metaphyseal-Diaphyseal Index score, change in resistance while insertion of the femur implants, inexperienced surgeons, uncemented femoral components, use of monoblock elliptical components, implantation of the acetabular components, patients with ankylosing spondylitis, female gender, uncemented stems in patients with abnormal proximal femoral anatomy and with cortices, different stem designs, heterogeneous fracture patterns and toothed design. Intraoperative fractures during THA were managed with cerclage wire, femoral revision, intramedullary nail and cerclage wires, use of internal fixation plates and screws for management of intra operative femur and acetabular fractures. The main reason for intraoperative fracture was found to be usage of cementless implants but planning and timely recognition of risk factors and evaluating them is important in management of intraoperative fractures. Adequate surgical site exposure is critical especially during dislocation of hip, reaming of acetabulum, impaction of implant and preparing the femoral canal for stem insertion. Eccentric and increased reaming of acetabulum to accommodate a larger cup is to be avoided, especially in females and elderly patients as the acetabulum is thinner. However, this area requires more research in order to obtain more evidence on effectiveness, safety and management of intraoperative fractures during THA

Prompt mobilisation after the Fracture neck of femur surgery is one of the important key performance index (‘KPI caterpillar charts’ 2021) affecting the overall functional outcome and mortality. Better control of peri-operative blood pressure and minimal alteration of renal profile as a result of surgery and anaesthesia may have an implication on early post-operative mobilisation. Aim was to evaluate perioperative blood pressure measurements (duration of fall of systolic BP below the critical level of 90mmHg) and effect on the post-operative renal profile with the newer short acting spinal anaesthetic agent (prilocaine and chlorprocaine) used alongside the commonly used regional nerve block. 20 patients were randomly selected who were given the newer short acting spinal anaesthetic agent along with a regional nerve block between May 2019 and February 2020. Anaesthetic charts were reviewed from all patients for data collection. The assessment criteria for perioperative hypotension: Duration of systolic blood pressure less than 90 mm of Hg and change of pre and post operative renal functions. Only one patient had a significant drop in systolic BP less than 90mmHg (25 minutes). 3 other patients had a momentary fall of systolic BP of less than 5 minutes. None of the above patients had mortality and had negligible change in pre and post op renal function. Only one patient in this cohort had elevation of post-operative creatinine levels but did not have any mortality. Only 1 patient died on day 3 post operatively who had multiple comorbidities and was under evaluation for GI cancer. Even in this patient the peri-operative blood pressure was well maintained (never below 90mmHg systolic) and post-operative renal function was also shown to have improved (309 pre-operatively to 150 post-operatively) in this patient. The use of short-acting spinal anaesthesia has shown to be associated with a better control of blood pressure and end organ perfusion, less adverse effects on renal function leading to early mobilisation and a more favourable patient outcome with reduced mortality, earlier mobilisation, shorter hospital stay and earlier discharge in this elderly patient cohort

Abstract. Introduction. Skeletal muscle wasting is an important clinical issue following acute traumatic injury, and can delay recovery and cause permanent functional disability particularly in the elderly. However, the fundamental mechanisms involved in trauma-induced muscle wasting remain poorly defined and therapeutic interventions are limited. Objectives. To characterise local and systemic mediators of skeletal muscle wasting in elderly patients following acute trauma. Methods. Experiments were approved by a local NHS Research Ethics Committee and all participants provided written informed consent. Vastus lateralis biopsies and serum samples were taken from human male and female patients shortly after acute trauma injury in lower limbs (n=6; mean age 78.7±4.4 y) and compared to age-matched controls (n=6; mean age 72.6±6.3 y). Atrogenes and upstream regulators (MuRF1; MAFbx; IL6, TNFα, PGC-1α) mRNA expression was assessed in muscle samples via RT-qPCR. Serum profiling of inflammatory markers (e.g. IL6, TNFα, IL1β) was further performed via multiplex assays. To determine whether systemic factors induced by trauma directly affect muscle phenotype, differentiated primary human myotubes were treated in vitro with serum from controls or trauma patients (pooled; n=3 each) in the final 24 hours of differentiation. Cells were then fixed, stained for myogenin and imaged to determine minimum ferret diameter. Statistical significance was determined at P<0.05. Results. There was an increase in skeletal muscle mRNA expression for E3 ligase MAFbx and inflammatory cytokine IL-6 (4.6 and 21.5-fold respectively; P<0.05) in trauma patients compared to controls. Expression of myogenic determination factor MyoD and regulator of mitochondrial biogenesis PGC-1α was lower in muscle of trauma patients vs controls (0.5 and 0.39-fold respectively; P<0.05). In serum, trauma patients showed increased concentrations of circulating pro-inflammatory cytokines IL-6 (14.5 vs. 0.3 pg/ml; P<0.05) and IL-16 (182.7 vs. 85.2 pg/ml; P<0.05) compared to controls. Primary myotube experiments revealed serum from trauma patients induced atrophy (32% decrease in diameter) compared to control serum-treated cells (P<0.001). Conclusion. Skeletal muscle from patients following acute trauma injury showed greater expression of atrophy and inflammatory markers. Trauma patient serum exhibited higher circulating pro-inflammatory cytokine concentrations. Primary human myotubes treated with serum from trauma patients showed significant atrophy compared to healthy serum-treated controls. We speculate a mechanism(s) acting via circulating factors may contribute to skeletal muscle pathology following acute trauma. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

This study aims to investigate that a single dose of tranexamic acid (TXA) will reduce blood loss and transfusion rates in elderly patients, undergoing intertrochanteric (IT) or femoral neck fractures surgery. Consecutive elderly patients receiving hip fracture surgery for stable or unstable IT fracture, treated with short intramedullary nail (IMN) insertion as well as cemented hemiarthroplasty for acute femoral neck (subcapital) hip fracture, were screened for inclusion in this single-centre randomized trial. Patients were randomly allocated to a study group by sealed envelope. One TXA dose of 15 mg/kg i.v. diluted in 100 ml N/S or one placebo dose i.v. in 100 ml N/S were administered 5 mins before the skin cut. Haemoglobin (Hb) concentration was measured at admission time and prior to surgery. Post-operatively it was measured on a daily basis until day 4, giving a total of four Hb measurements (days 1 to 4). The transfusion trigger point was determined in accordance with the French guidelines for erythrocyte blood transfusion. The transfusion trigger was 10 g/dl for patients at risk, while in all other cases, it was 9 g/dl. Information regarding the transfusions number was assessed directly by the hospital blood bank database. Blood loss was calculated by the Hb dilution method. Nadler's formula was used to calculate patients' blood volume. For calculation of total blood loss (TBL) expressed to total Hb loss and total Volume loss, the number of transfusions (55 grams of Hb per transfusion), the Hb concentration on preoperatively (Hgbi) and the Hb concentration on the last measure (Hgbe) were used. (Hb balance method). The primary efficacy outcome was the number of transfusions of allogeneic RBC from surgery up to day 4. The secondary ones were the total blood loss from surgery to day 4 as it was calculated by Hb-balance method. After randomization, 35 patients with femoral neck fracture and 30 patients with IT fracture received TXA prior to surgery. Respectively, 30 patients with femoral neck fracture and 55 with IT fracture didn't receive TXA. The groups did not differ significantly in their basic demographics (age, gender, BMI, injury mechanism, ASA score, co-morbidities). Results showed that patients undergoing hemiarthroplasty after receiving TXA, were transfused with less allogeneic RBC and had less total blood loss than patients that didn't receive TXA, but without statistical significance. While patients treated with IMN in the TXA group received a significantly lower number of RBC units than the control group (1.28 ± 1.049 vs 2.075 ± 1.685), (P = 0.0396), had a significantly lower loss of Hb (98.59 ± 55.24 vs 161.6 ± 141.7), (P = 0.0195) and a lower total blood volume loss (951.3 ± 598.9 ml vs 1513 ± 1247 ml), (P = 0.023). This trial confirmed TXA administration efficacy in reducing blood loss and transfusion rate in elderly patients undergoing hip fracture surgery. A TXA single dose may be a safer option, taking into account these patients' physiological status and co-morbidities

Introduction and Objective. Dislocation of a hip hemiarthroplasty is a significant complication with a high mortality rate in elderly patients. Previous studies have shown a higher risk of dislocation in patients with neuromuscular conditions. In this study, we reviewed our larger cohort of patients to identify if there is a link between neuromuscular disorders and dislocation of hip hemiarthroplasty in patients with neuromuscular conditions. Materials and Methods. We have retrospectively analysed a single-centre data that was collected over 34 years for patients with intracapsular neck of femur fracture who underwent hip hemiarthroplasty. The study population was composed of four groups: patients with no neuromuscular disorders, patients with Parkinson's disease, patients with previous stroke, and patients with mental impairment. Results. A total of 3827 patients were included in the analysis. 3371 patients had no neuromuscular condition (Group I) with a dislocation rate of 1.1%. 219 patients had Parkinsonism (Group II) with a dislocation rate of 3.2%, 104 patients had a previous stroke with weakness on the fracture side with a dislocation rate of 1.0% (Group III), and 984 patients had severe mental impairment with a dislocation rate of 1.8% (Group IV). The increased dislocation rate for those with Parkinson's disease was statistically significant (p=0.02) while none of the other neuromuscular conditions were statistically significant. Conclusions. Our study has shown an increased risk of dislocation of hemiarthroplasty in patients with Parkinson's disease in comparison to other groups. No increase was apparent for patients with mental impairment or weakness from a previous stroke

Geriatric syndromes could lead individuals to exhibit significant mobility and psychological deficits resulting in significant healthcare costs. Thus, identifying strategies to delay aging, or prevent progressive loss of tissue homeostasis could dramatically restore the function and independence of millions of elderly patients and significantly improve quality of life. One of the fundamental properties of aging is the accumulation of senescent cells and senescence associated secretory phenotypes (SASPs) that needs to be treated in wide range of therapeutics including orthobiologics. Senolytic compounds selectively target and kill senescent cells and inhibit anti-apoptotic pathways that are upregulated in senescent cells thereby inducing apoptotic cell death and abrogating systemic SASP factors. We have also shown that blocking fibrosis with Losartan (TGF-β1 blocker) can improve musculoskeletal healing and cartilage repair by reducing the amount of fibrosis. Thus, we hypothesize that administration of anti-fibrotic agents will enhance the beneficial effects of orthobiologics. The safety and efficacy of several senolytic and anti-fibrotic agents to delay age-related dysfunction and improve the function of orthobiologics have been demonstrated in a variety of animal models (in vivo). Overall, our innovative approaches target senescent cells (inflammation) and TGF-β1 (fibrosis) to enhance the clinical efficacy and use of orthobiologics for musculoskeletal repair. We will also discuss ongoing active clinical trials on orthobiologics to aiming at evaluating the safety and efficacy of senolytic agent (Fisetin) and anti-fibrotic agent (Losartan), used independently or in combination, to enhance the beneficial effects of orthobiologics for patients afflicted with musculoskeletal diseases and conditions

Introduction and Objective. Knee osteoarthritis (KOA) is a frequent disease for which therapeutic possibilities are limited. In current recommendations, the first-line analgesic is acetaminophen. However, low efficacy of acetaminophen, frequently leads to the use of weak opioids (WO) despite their poor tolerance, especially in elderly patients. The primary objective was to compare the analgesic efficacy and safety of a new wearable transcutaneous electrical nerve stimulation (W-TENS) to weak opioids (WO) in the treatment of moderate to severe, nociceptive, chronic pain in knee osteoarthritis patients. Materials and Methods. ArthroTENS study is a phase 3, non-inferiority, multicentric, prospective, randomized, single-blinded for primary efficacy outcome, controlled, in 2-parallel groups, clinical study comparing W-TENS versus WO over a 3-month controlled period with an additional, optional, non-controlled, 3-month follow-up for patients in W-TENS group. The co-primary outcome was KOA pain intensity (PI) at month 3 and the number of adverse events (AEs) over 3 months. Results. The non-inferiority of W-TENS was demonstrated in both the PP and ITT populations. At M3, PI in PP population was 3.87 (2.12) compared to 4.66 (2.37) (delta: −0.79 (0.44); 95% CI (−1.65; 0.08)) in W-TENS and WO groups, respectively. Since the absolute value of the 95% CI of the between-treatments mean PI difference [−1.71, – 0.12] was above 0 in ITT set, the planned superiority analysis was performed, demonstrating that W-TENS was significantly superior to WO at M3 (P=0.0124). At M1 and M3, the W-TENS group reached the absolute minimal clinically important difference (MCID) for an analgesic (1.8 (2.1) and 2.1 (2.3), respectively), corresponding to a 20 mm reduction in PI (interquartile range: 15–30) on a 0–100 mm visual analogic scale – i.e. 2 points on a numerical rating scale – which equates to “much better”. Conversely, in the WO group, a 0.5 (1.8) and a 1.1 (2.1) reduction in PI were observed at M1 and M3, respectively, while a 1-point reduction in PI is required to be considered as a “slightly better” improvement. In WO group, AEs were the common systemic AEs reported with WO (nausea, constipation, drowsiness, dizziness, pruritus, vomiting, dry mouth). AEs in W-TENS group were local, such as local cutaneous reaction (erythema). Thirty-nine (70.9%) patients wished to extend W-TENS treatment for 3 additional months. Only one patient discontinued this additional period and results were maintained at M6. Conclusions. W-TENS was more effective and better tolerated than WO in the treatment of nociceptive KOA chronic pain and could represent an interesting non-pharmacological alternative to WO

Introduction and Objective. Hip fractures represent one of the most challenging injuries in orthopaedic practice due to the associated morbidity, mortality and the financial burden they impose on the health care systems. By many still considered as the gold standard in the management of intertrochanteric fractures, the Dynamic Hip Screw utilizes controlled collapse during weight bearing to stabilize the fracture. Despite being a highly successful device, mechanical failure rate is not uncommon. The most accepted intraoperative indicator for lag screw failure is the tip apex distance (TAD), yet lateral femoral wall thickness (LWT) is another evolving parameter for detecting the potential for lateral wall fracture with subsequent medialization and implant failure. The aim of this study is to determine the mean and cut off levels for LWT that warrant lateral wall fracture and the implications of that on implant failure, revision rates and implant choice. Materials and Methods. This prospective cohort study included 42 patients with a mean age of 70.43y with intertrochanteric hip fractures treated with DHS fixation by the same consultant surgeon from April 2019 to December 2019. The study sample was calculated based on a confidence level of 90% and margin of error of 5%. Fracture types included in the study are 31A1 and 31A2 based on the AO/OTA classification system. LWT was assessed in all patients preoperatively using Surgimap (Nemaris, NY, USA) software. Patients were divided into two groups according to the post-operative integrity of the lateral femoral wall, where group (A) sustained a lateral femoral wall fracture intraoperatively or within 12 months after the index procedure, while in group (B) the lateral femoral wall remained intact. All patients were regularly followed up radiologically and clinically per the Harris Hip Score (HHS) for a period of 12 months. Results. At 12 months five patients (12%) suffered a postoperative lateral wall fracture, while in 37 patients (88%) the lateral femoral wall remained intact. The mean preoperative LWT of patients with a postoperative lateral wall fracture was 18.04 mm (SD ± 1.58) compared to 26.22mm (SD ± 5.93) in the group without a lateral wall fracture. All patients with post-operative lateral femoral wall fracture belong to 31A2 group, while 78.4% of the patients that did not develop post-operative lateral femoral wall fracture belong to 31A1 group. Eighty percent of patients in group (A) experienced shortening, collapse, shaft medialization and varus deformity. The mean Harris hip score of group (A) was 39.60 at 3 months and 65.67 at 6 months postoperatively, while that of group (B) was 80.75 and 90.65 at 3 and 6 months respectively, denoting a statistically significant difference (P<0.001). Treatment failure meriting a revision surgery was 40 % in group (A) and 8% in group (B) denoting a statistically significant difference (p<0.001). The cut-off point of LWT below which there is a high chance of post-operative lateral wall fracture when fixed with DHS is 19.6mm. This was shown on the receiver operating curve (ROC) by plotting the sensitivity against the 100 % specificity with a set 95% confidence interval 0.721 – 0.954. When lateral wall thickness was at 19.6 mm, the sensitivity was 100% and specificity was 81.8%. The area under the curve (AUC) was 0.838, which was statistically significant (P = 0.015). Conclusions. Preoperative measurement of LWT in elderly patients with intertrochanteric hip fractures is decisive. The cut off point for postoperative lateral wall fracture according to our study is 19.6 mm; hence, intramedullary fixation has to be considered in this situation

Introduction and Objective. In multiple trauma patients, as well as in the healing of isolated fractures (Fx) with heavy bleeding (trauma haemorrhage, TH), complications occur very often. This is particularly evident in elderly patients over 65 years of age. Since these accompanying circumstances strongly influence the clinical course of treatment, the influence of age on bone regeneration after femoral fracture and severe blood loss was investigated in this study. Materials and Methods. 12 young (17–26 weeks) and 12 old (64–72 weeks) male C57BL / 6J mice per group were examined. The fracture group Fx underwent an osteotomy after applying an external fixator. The THFx group also received blood pressure-controlled trauma hemorrhage (35 mmHg for 90 minutes) and reperfusion with Ringer's solution for 30 minutes. The Sham group received only the catheter and one external fixator. μCT scans of the femora were performed in vivo after 2 weeks and ex vivo after 3 weeks. Histological and biomechanical examinations were also carried out. The statistical significance was set at p ≤ 0.05. The non-normally distributed data were analyzed using the Mann-Whitney-U or Kruskal-Wallis test. Results. The histology showed less mineralized bone in the fracture gap in old animals of the Fx (25.41% [1.68%]) and THFx groups (25.50% [4.07%]) compared with the young ones (34.20% [6.36%], p = 0.003; 34.31% [5.12%], p=0.009). Moreover, a severe blood loss lead to more cartilage in both young (6.91% [5.08%]) and old animals (4.17% [1.42%]) compared to animals with only a fracture (2, 45% [1.04%], p=0.004; 2.95% [1.12%], p=0.032). In old animals (11.37 / nm. 2. [17.17 / nm. 2. ]) in contrast the young mice with an isolated fracture (33.6/nm. 2. [8.83/nm. 2. ]) fewer osteoclasts were present (p=0.009). Therefore, the severe blood loss further reduced the number of osteoclasts only in young animals (16.83/nm. 2. [6.07/nm. 2. ]) (p=0.004). In the in vivo μCT, after 2 weeks, a lower volume of bone, cortex and callus was found in old THFx animals (3.14 mm. 3. [0.64 mm. 3. ]); 1.01 mm. 3. [0.04 mm. 3. ]; 2.07 mm. 3. [0.57 mm. 3. ]) compared with the Fx animals (4.29 mm. 3. [0.74 mm. 3. ], p=0.008; 1.18 mm. 3. [0, 25 mm. 3. ], p=0.004; 3.02 mm. 3. [0.77 mm. 3. ], p=0.008) After 3 weeks, the ex vivo μCT scans also showed a reduced callus percentage in old THFx animals (61.18% [13.9 9%]), as well as a low number of trabeculae (1.81 mm. -1. [0.23 mm. -1. ]) compared to animals without blood loss (68.72% [15.71%], p = 0.030; 2.06mm. -1. [0.37mm. -1. ], p=0.041). In the biomechanical test, a reduced elasticity limit of the old THFx mice (7.75 N [3.33 N]) in contrast to the old Fx (10.24 N [3.32 N]) animals was shown (p=0.022). Conclusions. A severe blood loss has a higher negative effect on the healing, morphometry, and biomechanical properties of previously fractured femora in old compared to young individuals

Regeneration of bone defects in elderly patients is limited due to the decreased function of bone forming cells and compromised tissue physiology. Previous studies suggested that the regenerative activity of stem cells from aged tissues can be enhanced by exposure to young systemic and tissue microenvironments. The aim of our project was to investigate whether extracellular matrix (ECM) engineered from human induced pluripotent stem cells (hiPSCs) can enhance the bone regeneration potential of aged human bone marrow stromal cells (hBMSCs). ECM was engineered from hiPSC-derived mesenchymal-like progenitors (hiPSC-MPs), as well as young (70 years) hBMSCs. ECM structure and composition were characterized before and after decellularization using immunofluorescence and biochemical assays. Three hBMSCs of different ages were cultured on engineered ECMs. Growth and differentiation responses were compared to tissue culture plastic controls. Decellularized ECMs contained collagens type I and IV, fibronectin, laminin and < 5% residual DNA. Cultivation of young and aged hBMSCs on the hiPSC-ECM in osteogenic medium significantly increased hBMSC growth and markers of osteogenesis, including collagen deposition, alkaline phosphatase activity, bone sialoprotein expression and matrix mineralization compared to plastic controls. In aged BMSCs, matrix mineralization was only detected in ECM cultures in osteogenic medium. Comparison of ECMs engineered from hiPSC-MPs and hBMSCs of different ages suggested similar structure, composition and potential to enhance osteogenic responses in aged BMSCs. Our studies suggest that aged BMSCs regenerative activity can be enhanced by culture on hiPSC-engineered ECM

Hip fractures are a common injury in elderly patients. The UK has a National Hip Fracture Database to collect data on all patients presenting to hospital with a hip fracture. Literature evidence suggests that early surgery for hip fracture patients improves morbidity and mortality. UK national guidelines (BOA, NICE) recommend that surgery is performed within 36 hours of presentation and/or diagnosis for inpatients. Best Practice Tariffs ensure that hospitals are paid a set value if they meet this target of surgery within 36 hours. This study aims to look at reasons for delay to surgery for patients presenting to our busy level 2 trauma unit. This is a retrospective review of prospectively collected data for patients referred to the orthopaedic team at our hospital with a diagnosis of a neck of femur fracture between 1st April and 31st December 2018. Patients under the age of 65 year of age were excluded from our study. Only patients who were operated on after 36 hours were included. The database for reasons of surgical delay was reviewed and electronic patient records were used to collect further data on length of stay and 30-day mortality. A total of 249 patients were diagnosed with a hip fracture during the study period. 2 patients were too unwell for an operation and died within 24 hours of diagnosis/admission. 46 patients were included in the study. The primary reasons for surgical delay were patients not being fit for surgery (14/46) and the use of anti-coagulation (14/46). Other reasons included a lack of surgical capacity (7/46) and delayed diagnosis due to further imaging (CT). Mean delay to surgery was 51.8 hours (range 34.5 – 157.2 hours; median 42.9 hours), mean length of stay 20.4 days (range 5.3 – 55.7 days, median 15.6 days). 30-day mortality was 4/46 (8.6%) for patients who were delayed. Many of the issues we found in this study are unusual however these problems are commonly faced in many level 2 trauma units that serve an ever growing ageing population. Changing practice to provide improved out-of-hours medical care to facilitate medical optimisation and using current literature evidence that shows that the use of DOACs/NOACs does not adversely affect outcomes when patients are operated on within 24 hours of the last dose may help improve times to surgery