Aims. The aim of this meta-analysis was to assess the safety and efficacy of collagenase clostridium histolyticum compared with fasciectomy and percutaneous needle fasciotomy (PNF) for Dupuytren’s disease. Materials and Methods. We systematically searched PubMed, EMBASE, LILACS, Web of Science, Cochrane, Teseo and the ClinicalTrials.gov registry for clinical trials and cohort or case-control studies which compared the clinical outcomes and adverse effects of collagenase with those of fasciectomy or PNF. Of 1345 articles retrieved, ten were selected. They described the outcomes of 425 patients treated with collagenase and 418 treated by fasciectomy or PNF. Complications were assessed using inverse-variance weighted odds ratios (ORs). Clinical efficacy was assessed by differences between the means for movement of the joint before and after treatment. Dose adjustment was applied in all cases. Results. Random-effects modelling showed that patients treated with collagenase had 3.24 increased odds of adverse effects compared with those treated by fasciectomy (OR 4.39) or PNF (OR 1.72,). The effect was lost when only major complications were assessed. Joint movement analysis revealed a difference between means of less than 10%, indicating equivalent clinical efficacy in the short and medium term for collagenase and fasciectomy. We were unable to analyse this for PNF due to a shortage of data. Conclusion. There were no significant differences in effect size between collagenase and fasciectomy. The use of collagenase was associated with a higher overall risk of adverse effects than both fasciectomy and PNF. Cite this article: Bone Joint J 2018;100-B:73–80

Objectives. Insufficient protein ingestion may affect muscle and bone mass, increasing the risk of osteoporotic fractures in the elderly, and especially in postmenopausal women. We evaluated how a low-protein diet affects bone parameters under gonadal hormone deficiency and the improvement led by hormone replacement therapy (HRT) with 17β-oestradiol. Methods. Female Wistar rats were divided into control (C), ovariectomized (OVX), and 17β-oestradiol-treated ovariectomized (OVX-HRT) groups, which were fed a control or an isocaloric low-protein diet (LP; 6.6% protein; seven animals per group). Morphometric, serum, and body composition parameters were assessed, as well as bone parameters, mechanical resistance, and mineralogy. Results. The results showed that protein restriction negatively affected body chemical composition and bone metabolism by the sex hormone deficiency condition in the OVX group. The association between undernutrition and hormone deficiency led to bone and muscle mass loss and increased the fragility of the bone (as well as decreasing relative femoral weight, bone mineral density, femoral elasticity, peak stress, and stress at offset yield). Although protein restriction induced more severe adverse effects compared with the controls, the combination with HRT showed an improvement in minimizing these damaging effects, as it was seen that HRT had some efficacy in maintaining muscle and bone mass, preserving the bone resistance and minimizing some deleterious processes during the menopause. Conclusion. Protein restriction has adverse effects on metabolism, leading to more severe menopausal symptoms, and HRT could minimize these effects. Therefore, special attention should be given to a balanced diet during menopause and HRT. Cite this article: Bone Joint Res 2019;8:573–581

Adverse effects of different preparations of Botulinus Toxin were studied. 97 episodes of injections in 67 children with cerebral palsy carried out between 1994 and 2001 were available for study. A telephonic interview was carried out according to a format in which the nature of adverse effects and the onset and duration of beneficial effect were recorded. 52 children had diplegia, 27 had hemiplegia and 18 had quadriplegia. 69 injections were made using Botox and remainder were made using Dysport. The dose for botox was up to 12 units per kilogram body weight and for dysport up to 40 units per kilogram body weight. The average age at injection was 94 months. The diagnoses were evenly distributed between the groups. A total of 72 adverse effects were noted in 44 episodes. Botox group accounted for 35 episodes and dysport for 9 (p=0.23). Thirty-three children had at least one adverse effect. Botox group accounting for 23 and Dysport group for 10 (p=0.45). The commonest adverse effect was pain at the injection site. The student t test was carried out to test statistical significance. There were no significant differences in the occurrence of adverse effects or the onset and duration of beneficial effect. It may be concluded that botulinum therapy for cerebral palsy provided a high degree of patient/carer satisfaction. It produced few adverse effects and is generally well tolerated. The effects of botox and dysport were comparable

Regional anaesthesia, and the supplementation of either general or spinal anaesthesia with nerve block is well established and becoming increasingly more popular. Femoral, sciatic and obturator nerve blockade, in alone or in combination, by means of single shot or continuous infusion has been shown to significantly improve pain control and post operative nausea and vomiting (PONV). We identify equally significant morbidity associated with this practice, with delayed post operative rehabilitation, increase in length of stay, reduction in range of movement and local adverse symptoms at the site of injection and paraesthesia at 3 months post operatively. 2 surgeons were recruited to contribute 100 consecutive total knee replacements each to this study. Each worked exclusively with a one anaesthetist. Each had a predictable and different practice. One employed either spinal or general anaesthesia which the surgeon supplemented with end of operation infiltration of soft tissues in the surgical field including the capsule and skin incision with ropivacaine 300mg, adrenaline 500μg and ketorolac 30mg with normal saline added to make a volume of 100ml. The second employed either spinal or general anaesthesia but supplemented this with a single combined femoral and sciatic nerve block performed pre-operatively. Intravenous opiate analgesia administed via patient controlled analgesia pump for 24 hours post operatively, paracetamol 1g 6 hourly and ibuprofen 300mg 8 hourly where appropriate were prescribed by both anaesthetists. We recorded the incidence of insertion of urinary catheter, deep venous thrombosis diagnosed within 3 and 12 weeks, recovery of lower limb power to grade 5/5, range of movement achieved in each postoperative day and at 12 weeks post operatively, length of stay in addition to PONV and pain scores using the visual analogue scale (VAS) and collected every 6 hours. Localised pain and tenderness at the site of injection was noted at 12 weeks, and persistent paraesthesia. As predicted patients in the group receiving nerve block has significantly less pain and post operative nausea and vomiting (p< 0.05). There was no statistically significant difference in the use of urinary catheters (p = 0.052) or the incidence of deep venous thrombosis (p=0.58). There was however a significant difference in the recovery of lower limb power (p = 0.023), range of movement recorded at 24hr intervals (p=0.038) (at 12 weeks p=0.54) and length of stay in hospital (0.038). One patient had an almost complete femoral nerve palsy at 12 weeks and required a manipulation under anaesthesia of her knee following recovery of same. Nerve blockade is an increasingly popular method of controlling post-operative pain. We demonstrate some adverse effects on rehabilitation following this practice in addition to the increased financial and logistical burden of a longer inpatient stay

Introduction: Polymodal anaesthesia has become the core approach for the modern anaesthetist. Femoral, sciatic and obturator nerve blockade, individually or in combination, by means of either single shot or continuous infusion, are often used as adjuncts to general anaesthesia in knee arthroplasty.

Methods: We examine the outcome of 2 groups of 100 patients from 2 surgeons and their anaesthetists. All patients received a general anaesthetic. The first group receive a single shot femoral and sciatic nerve block, the second group a standard GA and local infiltration of the surgical field. Post operatively, both groups received identical analgesic regimes and rehabilitation programmes.

Results: Length of stay was prolonged in the nerve blockade group, with 21 of the 100 patients still in hospital on day 6 versus 9 patients in the local infiltration group. An initial advantage in flexion and extension in the nerve blockade group was reversed by day 2 and persisted thereafter. Motor dysfunction was seen to be more prevalent and of longer duration in the nerve blockade group. Muscle groups supplied by the sciatic nerve were 4 times more likely to be involved than those supplied by the femoral nerve. Dysaesthesia in the sciatic nerve dermatomes was 5 times more likely within the nerve blockade group, but less likely in the local infiltration group. No significant difference in rates of VTE. Pain control was superior and less analgesia was required in the nerve blockade group. Fewer patients required urethral catheterisation in the local infiltration group. One heel ulcer occurred in the nerve blockade group. Tourniquet time, significant as a possible contributor to nerve injury, was similar.

Conclusion: Nerve blockade in knee arthroplasty not recommended.

In 2005, we demonstrated that the polished triple-tapered C-stem at two years had migrated distally and rotated internally. From that series, 33 patients have now been followed radiologically, clinically and by radiostereometric analysis (RSA) for up to ten years. The distal migration within the cement mantle had continued and reached a mean of 2 mm (0.5 to 4.0) at ten years. Internal rotation, also within the cement mantle, was a mean 3.8° (external 1.6° to internal 6.6°) The cement mantle did not show any sign of migration or loosening in relation to the femoral bone. There were no clinical or radiological signs indicating that the migration or rotation within the cement mantle had had any adverse effects for the patients. Cite this article: Bone Joint J 2014;96-B:604–8

We examined the outcomes and levels of patient satisfaction in 202 consecutive cases of ultrasound-guided supraclavicular brachial plexus block (SBPB) in upper limb surgery performed between September 2007 and March 2010.

All blocks were performed by orthopaedic surgeons using ultrasound visualisation with a high-frequency linear probe. The probe was placed in the coronal–oblique plane in the supraclavicular fossa, and the puncture was ‘in-plane’ from lateral to medial. Most of the blocks were performed with 0.75% ropivacaine/1% lidocaine (1:1), with or without adrenaline in 1:200 000 dilution. In 201 patients (99.5%) the brachial plexus block permitted surgery without conversion to general anaesthesia. The mean procedure time for block was 3.9 min (2 to 12), the mean waiting time for surgery was 34.1 min (10 to 64), the mean surgical time was 75.2 min (6 to 232), and the mean duration of post-anaesthetic analgesia was 437 min (171 to 992). A total of 20 patients (10%) developed a transient Horner’s syndrome. No nerve injury, pneumothorax, arterial puncture or systemic anaesthetic toxicity were recorded. Most patients (96.7%) were satisfied with ultrasound-guided SBPB. This study demonstrates the efficacy and safety of ultrasound-guided SBPB for orthopaedic surgery on the upper limb.

Cite this article: Bone Joint J 2014;96-B:795–9.

The aim of this scoping review is to understand the extent and type of evidence in relation to the use of guided growth for correcting rotational deformities of long bones. Guided growth is routinely used to correct angular deformities in long bones in children. It has also been proven to be a viable method to correct rotational deformities, but the concept is not yet fully examined. Databases searched include Medline, Embase, Cochrane Library, Web of Science and Google Scholar. All identified citations were uploaded into Rayyan.ai and screened by at least two reviewers. The search resulted in 3569 hits. 14 studies were included: 1 review, 3 clinical trials and 10 pre-clinical trials. Clinical trials: a total of 21 children (32 femurs and 5 tibiae) were included. Surgical methods were 2 canulated screws connected by cable, PediPlates obliquely oriented, and separated Hinge Plates connected by FiberTape. Rotation was achieved in all but 1 child. Adverse effects reported include limb length discrepancy (LLD), knee stiffness and rebound of rotation after removal of tethers. 2 pre-clinical studies were ex-vivo studies, 1 using 8-plates on Sawbones and 1 using a novel z-shaped plates on human cadaver femurs. There were 5 lapine studies (2 using femoral plates, 2 using tibial plates and 1 using an external device on tibia), 1 ovine (external device on tibia), 1 bovine (screws and cable on metacarp) and a case-report on a dog that had an external device spanning from femur to tibia. Rotation was achieved in all studies. Adverse effects reported include implant extrusions, LLD, articular deformities, joint stiffness and rebound. All included studies conclude that guided growth is a viable treatment for rotational deformities of long bones, but there is great variation in models and surgical methods used, and in reported adverse effects

Interscalene brachial plexus block is the standard regional analgesic technique for shoulder surgery. Given its adverse effects, alternative techniques have been explored. Reports suggest that the erector spinae plane block may potentially provide effective analgesia following shoulder surgery. However, its analgesic efficacy for shoulder surgery compared with placebo or local anaesthetic infiltration has never been established. We conducted a randomised controlled trial to compare the analgesic efficacy of pre-operative T2 erector spinae plane block with peri-articular infiltration at the end of surgery. Sixty-two patients undergoing arthroscopic shoulder repair were randomly assigned to receive active erector spinae plane block with saline peri-articular injection (n = 31) or active peri-articular injection with saline erector spinae plane block (n = 31) in a blinded double-dummy design. Primary outcome was resting pain score in recovery. Secondary outcomes included pain scores with movement; opioid use; patient satisfaction; adverse effects in hospital; and outcomes at 24 h and 1 month. There was no difference in pain scores in recovery, with a median difference (95%CI) of 0.6 (-1.9-3.1), p = 0.65. Median postoperative oral morphine equivalent utilisation was significantly higher in the erector spinae plane group (21 mg vs. 12 mg; p = 0.028). Itching was observed in 10% of patients who received erector spinae plane block and there was no difference in the incidence of significant nausea and vomiting. Patient satisfaction scores, and pain scores and opioid use at 24 h were similar. At 1 month, six (peri-articular injection) and eight (erector spinae plane block) patients reported persistent pain. Erector spinae plane block was not superior to peri-articular injection for arthroscopic shoulder surgery

Prophylactic antibiotics are important in reducing the risk of periprosthetic joint infection (PJI) following total knee arthroplasty. Their effectiveness depends on the choice of antibiotic and the optimum timing of their administration, to ensure adequate tissue concentrations. Cephalosporins are typically used, but an increasing number of resistant organisms are causing PJI, leading to the additional use of vancomycin. There are difficulties, however, with the systemic administration of vancomycin including its optimal timing, due to the need for prolonged administration, and potential adverse reactions. Intraosseous regional administration distal to a tourniquet is an alternative and attractive mode of delivery due to the ease of obtaining intraosseous access. Many authors have reported the effectiveness of intraosseous prophylaxis in achieving higher concentrations of antibiotic in the tissues compared with intravenous administration, providing equal or enhanced prophylaxis while minimizing adverse effects. This annotation describes the technique of intraosseous administration of antibiotics and summarizes the relevant clinical literature to date. Cite this article: Bone Joint J 2023;105-B(11):1135–1139

There are a number of patients in whom hip preservation surgery is not indicated as they have developed signs of early osteoarthritis, and nor can they have a hip replacement as they are too early in the disease process. The use of PRP in OA of the hip has not been studied systematically and this study concisely collates all the available data in the use of PRP in Hip OA. This systematic review and meta-analysis aimed to assess intra-articular platelet-rich plasma as a therapeutic intervention for hip osteoarthritis, including the duration of efficacy, influence of dose and composition of PRP, and the incidence of adverse effects. We performed literature searches on the MEDLINE, EMBASE, CINHAL, WEB OF SCIENCE, COCHRANE and SCOPUS databases, and PRSIMA guidelines were followed. Data was pooled using random effects meta-analysis. We assessed quality of the included studies using the Methodological Index for Non-Randomised Studies (MINORS) instrument, with an additional assessment for Randomised Controlled Trials with the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Eight studies were included in the analysis, with data from a total of 331 patients. PRP significantly reduced pain compared to baseline at multiple timepoints, with the greatest effect at 1–2mo follow-up. PRP only significantly improved function at the 1–2mo follow-up. A significantly larger reduction in pain was achieved with a single injection or PRP compared to multiple injections, a total injected dose of PRP <15mL compared to ≥15mL or using a leukocyte-poor PRP preparation compared to leukocyte-rich PRP. There were no lasting adverse effects. Low and moderate quality evidence suggests that PRP reduces pain and improves function at endpoint compared to baseline. Moderate quality evidence suggests a larger reduction in pain is achieved with a single injection of PRP compared to multiple injections, and low quality evidence attributes a larger reduction of pain with a total injected dose of PRP <15mL compared to ≥15mL or using leukocyte-poor PRP compared to leukocyte-rich PRP

Unicompartmental knee arthroplasty (UKA) has a higher risk of revision than total knee arthroplasty, particularly for low volume surgeons. The recent introduction of robotic-arm assisted systems has allowed for increased accuracy, however new systems typically have learning curves. The objective of this study was to determine the learning curve of a robotic-arm assisted system for UKA. Methods A total of 152 consecutive robotic-arm assisted primary medial UKA were performed by five surgeons between 2017 and 2021. Operative times, implant positioning, reoperations and patient-reported outcome measures (PROMS; Oxford Knee Score, EuroQol-5D, and Forgotten Joint Score) were recorded. There was a learning curve of 11 cases with the system that was associated with increased operative time (13 minutes, p<0.01) and improved insert sizing over time (p=0.03). There was no difference in implant survival (98.2%) between learning and proficiency phases (p = 0.15), and no difference in survivorship between ‘high’ and ‘low’ usage surgeons (p = 0.23) at 36 months. There were no differences in PROMS related to the learning curve. This suggested that the learning curve did not lead to early adverse effects in this patient cohort. The introduction of a robotic-arm assisted UKA system led to learning curves for operative time and implant sizing, but there was no effect on patient outcomes at early follow- up. The short learning curve was independent of UKA usage and indicated that robotic-arm assisted UKA may be particularly useful for low-usage surgeons

Stem cell therapy is an effective means to address the repair of large segmental bone defects. However, the intense inflammatory response triggered by the implants severely impairs stem cell differentiation and tissue regeneration. High-dose transforming growth factor β1 (TGF-β1), the most locally expressed cytokine in implants, inhibits osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and promotes tissue fibrosis, severely compromising the efficacy of stem cell therapy. Small molecule inhibitors of TGF-β1 can be used to ameliorate the osteogenic disorders caused by high concentrations of TGF-β1, but systemic inhibition of TGF-β1 function will cause strong adverse effects. How to find safe and reliable molecular targets to antagonize TGF-β1 remains to be elucidated. Orphan nuclear receptor Nr4a1, an endogenous inhibitory molecule of TGF-β1, suppresses tissue fibrosis, but its role in BMSC osteogenesis is unclear. We found that TGF-β1 inhibited Nr4a1 expression through HDAC4. Overexpression of Nr4a1 in BMSCs reversed osteogenic differentiation inhibited by high levels of TGF- β1. Mechanistically, RNA sequencing showed that Nr4a1 activated the ECM-receptor interaction and Hippo signaling pathway, which in turn promoted BMSC osteogenesis. In bone defect repair and fracture healing models, transplantation of Nr4a1-overexpressing BMSCs into C57BL/6J mice or treatment with the Nr4a1 agonist Csn-B significantly ameliorated inflammation-induced bone regeneration disorders. In summary, our findings confirm the endogenous inhibitory effect of Nr4a1 on TGF- β1 and uncover the effectiveness of Nr4a1 agonists as a therapeutic tool to improve bone regeneration, which provides a new solution strategy for the treatment of clinical bone defects and inflammatory skeletal diseases

Abstract. Objectives. To determine the effectiveness of LIA compared to ACB in providing pain relief and reducing opiates usage in hamstring graft ACL reconstructions. Materials and Methods. In a consecutive series of hamstring graft ACL reconstructions, patients received three different regional and/or anaesthetic techniques for pain relief. Three groups were studied: group 1: general anaesthetic (GA)+ ACB (n=38); group 2: GA + ACB + LIA (n=31) and group 3: GA+LIA (n=36). ACB was given under ultrasound guidance. LIA involved infiltration at skin incision site, capsule, periosteum and in the hamstring harvest tunnel. Analgesic medications were similar between the three groups as per standard multimodal analgesia (MMA). Patients were similar in demographics distribution and surgical technique. The postoperative pain and total morphine requirements were evaluated and recorded. The postoperative pain was assessed using the visual analogue scores (VAS) at 0hrs, 2hrs, 4hrs, weight bearing (WB) and discharge (DC). Results. There was no statistically significant difference in opiates intake amongst the three groups. When comparing VAS scores; there were no statistical difference between the groups at any of the time intervals that VAS was measured. However, the GA+LIA group hospital's LOS (m=2.31hrs, SD=0.75) was almost half that of GA+ACB group (m=4.24hrs, SD=1.08); (conditions t(72)=8.88; p=0.000). There was no statistical significance in the incidence of adverse effects amongst the groups. Conclusion. The LIA technique provided equally good pain relief following hamstring graft ACL reconstructions when compared to ACB, while allowing for earlier rehabilitation, mobilisation and discharge

Surgical site infections following orthopaedic surgery are a serious complication associated with increased morbidity and mortality. Intra-wound antibiotic powder may be able to provide infection prophylaxis locally with less systemic adverse effects, and promising results have been reported in systematic reviews of its use in spine surgery. This study aims to analyse the efficacy and adverse effect profile of intra-wound antibiotics in reducing surgical site infections in orthopaedic surgery for traumatic pelvic and lower limb fractures. A systematic review was conducted for studies reporting on the incidence of surgical site infections following administration of intra-wound antibiotic powder in pelvic and lower limb trauma surgery. Randomised controlled trials, cohort and case-control studies were included. A meta-analysis was conducted for deep surgical site infections. Seven studies were included in the systematic review including six retrospective case-control studies and one randomised controlled trial. Results of the meta-analysis suggest a potential 23% reduction in the odds of developing a deep surgical site infection in patients treated with intra-operative antibiotic powder compared with those managed with intravenous antibiotics alone (OR 0.77, 95% CI 0.52 – 1.13), although the results did not reach statistical significance. Notable selective bias against intra-wound antibiotics and suboptimal study design were found in the retrospective studies, however the randomised controlled trial reported a significant reduction in deep surgical site infections with intra-wound vancomycin powder. There were no reports of systemic adverse outcomes and minimal risk of wound complications with the use of intra-wound antibiotics. This review suggests the use of intra-wound antibiotic powder in pelvic and lower limb trauma surgery may reduce the incidence of deep surgical site infections. Further powered studies including randomised controlled trials are required to confirm the results highlighted in this study

Our previous rat study demonstrated an ex vivo-created “Biomimetic Hematoma” (BH) that mimics the intrinsic structural properties of normal fracture hematoma, consistently and efficiently enhanced the healing of large bone defects at extremely low doses of rhBMP-2 (0.33 μg). The aim of this study was to determine if an extremely low dose of rhBMP-2 delivered within BH can efficiently heal large bone defects in goats. Goat 2.5 cm tibial defects were stabilized with circular fixators, and divided into groups (n=2-3): 2.1 mg rhBMP-2 delivered on an absorbable collagen sponge (ACS); 52.5 μg rhBMP-2 delivered within BH; and an empty group. BH was created using autologous blood with a mixture of calcium and thrombin at specific concentrations. Healing was monitored with X-rays. After 8 weeks, femurs were assessed using microCT. Using 2.1 mg on ACS was sufficient to heal 2.5 cm bone defects. Empty defects resulted in a nonunion after 8 weeks. Radiographic evaluation showed earlier and more robust callus formation with 97.5 % (52.5 μg) less of rhBMP-2 delivered within the BH, and all tibias were fully bridged at 3 weeks. The bone mineral density was significantly higher in defects treated with BH than with ACS. Defects in the BH group had smaller amounts of intramedullary and cortical trabeculation compared to the ACS group, indicating advanced remodeling. The results confirm that the delivery of rhBMP-2 within the BH was much more efficient than on an ACS. Not only did the large bone defects heal consistently with a 40x lower dose of rhBMP-2, but the quality of the defect regeneration was also superior in the BH group. These findings should significantly influence how rhBMP-2 is delivered clinically to maximize the regenerative capacity of bone healing while minimizing the dose required, thereby reducing the risk of adverse effects

The multimodal management of canal stenosis is increasing, and inhibitors of central sensitization are playing a crucial role in central sensitization processes. Pregabalin and gabapentin are antiepileptic drugs that reduce presynaptic excitability. The objective of this study was to investigate whether the use of pregabalin and gabapentin is effective in the symptomatic management of canal stenosis. A literature search was conducted in four databases. The inclusion criteria were studies that compared pregabalin or gabapentin with a control group in lumbar canal stenosis. Randomized clinical trials and a comparative retrospective cohort study were included. The main clinical endpoints were VAS/NRS, ODI, and RDQ (Roland Morris Disability Questionnaire) at 2, 4, 8 weeks, and 3 months, adverse events, and walking distance were also collected. Data were combined using Review Manager 5.4 software. Six studies and 392 patients were included. The mean age was 60.25. No significant differences were observed in VAS at 2, 4, and 8 weeks: (MD: 0.23; 95% CI: −0.63-1.09), (MD: −0.04; 95% CI: −0.64 to −0.57), and (MD: −0.6; 95% CI: −1.22 to 0.02). Significant differences were observed in favor of pregabalin with respect to VAS at three months: (MD: −2.97; 95% CI: −3.43 to −2.51). No significant differences were observed in ODI (MD: −3.47; 95% CI: −7.15 to −0.21). Adverse events were significantly higher in the pregabalin/gabapentin group (OR 5.88, 95%CI 1.28-27.05). Walking distance and RDQ could not be compared, although the results were controversial. Gabapentinoids have not been shown to be superior to other drugs used in the treatment of LSS or to placebo. However, they have shown a higher incidence of adverse effects, improved results in VAS at 3 months, and a slight improvement in ambulation at 4 months in combination with NSAIDs compared to NSAIDs in monotherapy

The signaling molecule prostaglandin E2 (PGE2), synthesized by cyclooxygenase-2 (COX-2), is immunoregulatory and reported to be essential for skeletal stem cell function. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in osteoarthritis (OA) analgesia, but cohort studies suggested that long-term use may accelerate pathology. Interestingly, OA chondrocytes secrete high amounts of PGE2. Mesenchymal stromal cell (MSC) chondrogenesis is an in vitro OA model that phenocopies PGE2 secretion along with a hypertrophic OA-like cell morphology. Our aim was to investigate cause and effects of PGE2 secretion in MSC-based cartilage neogenesis and hypertrophy and identify molecular mechanisms responsible for adverse effects in OA analgesia. Human bone marrow-derived MSCs were cultured in chondrogenic medium with TGFβ (10ng/mL) and treated with PGE2 (1µM), celecoxib (COX-2 inhibitor; 0.5µM), AH23848/AH6809 (PGE2 receptor antagonists; 10µM), or DMSO as a control (n=3–4). Assessment criteria were proteoglycan deposition (histology), chondrocyte/hypertrophy marker expression (qPCR), and ALP activity. PGE2 secretion was measured (ELISA) after TGFβ withdrawal (from day 21, n=2) or WNT inhibition (2µM IWP-2 from day 14; n=3). Strong decrease in PGE2 secretion upon TGFβ deprivation or WNT inhibition identified both pathways as PGE2 drivers. Homogeneous proteoglycan deposition and COL2A1 expression analysis showed that MSC chondrogenesis was not compromised by any treatment. Importantly, hypertrophy markers (COL10A1, ALPL, SPP1, IBSP) were significantly reduced by PGE2 treatment, but increased by all inhibitors. Additionally, PGE2 significantly decreased ALP activity (2.9-fold), whereas the inhibitors caused a significant increase (1.3-fold, 1.7-fold, 1.8-fold). This identified PGE2 as an important inhibitor of chondrocyte hypertrophy. Although TGFβ and WNT are known pro-arthritic signaling pathways, they appear to induce a PGE2-mediated antihypertrophic effect that can counteract pathological cell changes in chondrocytes. Hampering this rescue mechanism via COX inhibition using NSAIDs thus risks acceleration of OA progression, indicating the need of OA analgesia adjustment

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

In patients admitted to hospital with a hip fracture, urinary issues are common. Despite guidelines that recommend avoiding foley catheter usage when possible, it remains a common part of perioperative care. To date, there is no prospective data on the safety and satisfaction associated with catheter use in such cohort. The aim of this study was to evaluate the satisfaction of patients when using a foley catheter while they await surgery for their fractured hip and the safety associated with catheter use. In our prospectively collected database, 587 patients were admitted to our tertiary care center over a 1 year period. Most patients (328) were catheterized within the first 24h of admission, primarily inserted in ED. Of these patients, 119 patients (61 catheterized and 58 noncatheterized) completed a questionnaire about their perioperative management with foley catheter usage administered on day 1 of admission. This was used to determine satisfaction of catheter use (if catheterized) and pain levels (associated with catheterized or associated with transferring/voiding if not catheterized). Adverse effects related with catheter use included urinary tract infection (UTI) and post-operative urinary retention (POUR). Ninety-five percent of patients found the catheter to be convenient. Only 5% of patients reported any pain with catheter use. On the contrary, 47.5% of non-catheterized patients found it difficult to move to the bathroom and 30.4% found it difficult to urinate. Catheterized patients had significative less pain than uncatheterized patients (0.62/10 vs 2.45/10 respectively, p < 0 .001). The use of nerve block reduced pain levels amongst catheterized patients but was not associated with reduced pain levels or satisfaction amongst non-catheterized patients. The use of catheter was not associated with increased risk of UTI(17.5% in the catheterized vs 13.3% in the non-catheterized, p = 0.541) or POUR (6.8% in the catheterized vs 11.1% in the non-catheterized, p = 0.406). This study illustrates the benefits and safety associated with the use of urinary catheters in the pre-operative period amongst hip fractures. The use of catheters was associated with reduced pain and satisfaction without increasing post-operative UTI or POUR. These findings suggest that pre-operative catheter use is associated with less pain and more satisfaction for patients awaiting hip surgery and whom other measures, such as nerve blocks, are unlikely to reduce the discomfort associated with the mobility required to void. A prospective randomized control study could lead to a more evidence based approach for perioperative foley catheter usage in hip fracture patients