Changing Pain Management Strategy from Opioid-centric Towards Improve Postoperative Cognitive Dysfunction with Dexmedetomidine.

OBJECTIVE: This study was aimed to investigate the effectiveness of dexmedetomidine (DEX) on improving the level of pain and disability to find out the possible correlation between psychological factors with pain management satisfaction and physical function in patients with femoral neck fractures. METHODS: One hundred twenty-four adult patients with stable femoral neck fractures (type I and II, Garden classification) who underwent internal fixation, were prospectively enrolled including 62 patients in the DEX group and 62 patients in the control group. The magnitude of disability using Harris Hip Score, Postoperative Cognitive Dysfunction (POCD) using Mini-Mental State Examination (MMSE score), Quality of Recovery (QoR-40), pain-related anxiety (PASS-20), pain management and pain catastrophizing scale (PCS) were recorded on the first and second day after surgery. RESULTS: The DEX group on the first and second days after surgery exhibited higher quality of recovery scores, greater satisfaction with pain management, low disability scores, less catastrophic thinking, lower pain anxiety, greater mini mental state examination scores and less opioid intake and the differences were statistically significant compared with the control group (P<0.001). Emergence agitation and incidence of POCD were significantly less in the DEX group (P<0.001). Decreased disability was associated with less catastrophic thinking and lower pain anxiety, but not associated with more opioid intake (P<0.001). Higher QoR-40 scores had a negative correlation with more catastrophic thinking and more opioid intake (P<0.001). Greater satisfaction with pain management was correlated with less catastrophic thinking and less opioid intake (P<0.001). CONCLUSION: Using DEX as an adjunct to anesthesia could significantly improve postoperative cognitive dysfunction and the quality of recovery and these improvements were accompanied by decrease in pain, emergence agitation, and opioid consumption by DEX administration. Since pain relief and decreased disability were not associated with prescribing greater amounts of opioid intake in the patients, improving psychological factors, including reducing catastrophic thinking or self-efficacy about pain, could be a more effective strategy to reduce pain and disability, meanwhile reducing opioid prescription in the patients. Our findings showed that DEX administration is safe sedation with anti-inflammatory, analgesic and antiemetic effects and it could help change pain management strategy from opioidcentric towards improved postoperative cognitive dysfunction.

Successful treatment for bilateral femoral neck insufficiency fractures: a rare lesion case report and an updated review of the literature.

BACKGROUND: The incidence of insufficiency fracture (IF) at femoral neck is low, accounting for about 5% of all insufficiency fractures, and IF at bilateral femoral neck is less common with more occurrence in athlete or serviceman. With the aging of populations, more cases of bilateral femoral neck IF have occurred recently, while the standard clinical treatment still remains lacking due to the complexity of these patients. CASE PRESENTATION: A 55-year-old male patient complained pain in his bilateral hip, with no history of trauma, glucocorticoid hormone consumption or radiotherapy, and imaging examination revealed fracture nonunion and shortening in his left femoral neck, and double fracture line on the right femoral neck. The patient received a cementless THA for the left femoral neck fracture and conservative treatment for the right side, followed by Elcatonin injection and oral administration of Carbonate D3 Granules. After 4 months of fellow-up, the patient presented improved functional scorings in bilateral hip joints, with no signs of prothesis infection or loosening. CONCLUSION: We present a rare case of bilateral femoral neck IF in a middle-aged male and the treatment is successful. The timely CT and MRI examinations of bilateral hip joints for patients was necessary for orthopedists to select proper therapeutic regimen. In addition, the choice for therapeutic regimen of bilateral femoral IF should not only be based on the professional judgement of orthopedists, but also on the wishes of patients.

Evaluation of the Implementation of Guidelines on the Treatment of Osteoporosis in Patients with Rheumatoid Arthritis.

OBJECTIVE: To assess whether the 2003 and 2014 French guidelines on the prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) and the 2012 update of the French guidelines for the treatment of postmenopausal osteoporosis (PMOP) were applied in patients with rheumatoid arthritis (RA). METHODS: We conducted a cross-sectional study of 776 patients with RA (19 centers). We collected the data required for the application of the various recommendations (age, sex, prednisone intake, low-energy fracture, history in the immediate family of hip fractures, and bone densitometry), anti-osteoporotic drugs, and the various factors that may be associated with the application of the recommendations. RESULTS: Of the patients who should have received antiosteoporosis treatment, there were 22.6% actually treated (according to the 2014 guidelines), 27.3% actually treated according to the 2003 guidelines, and of postmenopausal women, 23.6% (according to the 2012 PMOP guidelines). Applying the 2014 GIOP guidelines increased the theoretical number of patients requiring treatment relative to the 2003 GIOP guidelines (77% vs 53%; p < 0.001). In multivariate analysis, being treated was associated with a spinal T score ≤ -2 SD according to the 2014 guidelines; with not taking part in physical activity for more than 30 min a day according to the 2003 guidelines; and with older age, lower body mass index, and a T score ≤ -2.5 SD in at least 1 site according to the PMOP guidelines. CONCLUSION: Patients with RA had inadequate prevention of GIOP and PMOP. The management of osteoporosis needs to be improved in this population.

Topical cutaneous application of carbon dioxide via a hydrogel for improved fracture repair: results of phase I clinical safety trial.

BACKGROUND: Clinicians have very limited options to improve fracture repair. Therefore, it is critical to develop a new clinically available therapeutic option to assist fracture repair biologically. We previously reported that the topical cutaneous application of carbon dioxide (CO2) via a CO2 absorption-enhancing hydrogel accelerates fracture repair in rats by increasing blood flow and angiogenesis and promoting endochondral ossification. The aim of this study was to assess the safety and efficacy of CO2 therapy in patients with fractures. METHODS: Patients with fractures of the femur and tibia were prospectively enrolled into this study with ethical approval and informed consent. The CO2 absorption-enhancing hydrogel was applied to the fractured lower limbs of patients, and then 100% CO2 was administered daily into a sealed space for 20 min over 4 weeks postoperatively. Safety was assessed based on vital signs, blood parameters, adverse events, and arterial and expired gas analyses. As the efficacy outcome, blood flow at the level of the fracture site and at a site 5 cm from the fracture in the affected limb was measured using a laser Doppler blood flow meter. RESULTS: Nineteen patients were subjected to complete analysis. No adverse events were observed. Arterial and expired gas analyses revealed no adverse systemic effects including hypercapnia. The mean ratio of blood flow 20 min after CO2 therapy compared with the pre-treatment level increased by approximately 2-fold in a time-dependent manner. CONCLUSIONS: The findings of the present study revealed that CO2 therapy is safe to apply to human patients and that it can enhance blood flow in the fractured limbs. TRIAL REGISTRATION: This study has been registered in the UMIN Clinical Trials Registry (Registration number: UMIN000013641, Date of registration: July 1, 2014).

Ultrasound-guided femoral nerve blocks are not superior to ultrasound-guided fascia iliaca blocks for fractured neck of femur.

OBJECTIVE: To determine if an ultrasound-guided femoral nerve block (FNB) is superior to an ultrasound-guided fascia iliaca compartment block (FICB) in providing pain relief to patients with a neck of femur or proximal femoral fracture. METHODS: A double-blind randomised controlled trial was conducted. All participants received two blocks, one active and one placebo. An active FICB was administered to 52 participants and 48 participants received an active FNB. RESULTS: Analysis was completed on data collected from 100 participants. Most patients were elderly and the majority were female. Both FICB and FNB achieved clinically significant mean reductions in pain scores (2.62 for FICB and 2.3 for FNB). There was no significant difference in reduction in pain scores between the two cohorts, P = 0.408. CONCLUSIONS: Ultrasound-guided FNB is not superior to ultrasound-guided FICB, with both facilitating an equivalent analgesia effect in patients with a neck of femur or proximal femur fracture.

Phospholipase C signaling activated by parathyroid hormone mediates the rapid osteoclastogenesis in the fracture healing of orchiectomized mice.

BACKGROUND: The age-related osteoporosis is an increasing risk severely threatening the live quality of aged people. Human parathyroid hormone (hPTH) is applied to the therapy of osteoporosis successfully, however, the mechanism, especially the signaling pathway activated in the healing fracture by PTH is still unknown. METHODS: The once daily injections of hPTH(1-34) and GR (1-34) (the PLC deficient analog) into the orchiectomized male mice with bone fracture, were started at the second day after fracture and lasted for 4 weeks. To explore the role of phospholipase C signaling in the androgen-deficient fracture healing, the fracture healing were evaluated via radiography, micro-CT, biomechanics testing, serum biochemistry, bone marrow cell culture and gene expression quantification. RESULTS: After two weeks of fracture, both peptides significantly increased bone mineral density (BMD), bone mass content (BMC) and bone volume (BV/TV) in the healing area. However, compared to hPTH(1-34), GR(1-34) induced more woven bones, the higher BMC and BMD, as well as the less serum TRAP and osteoclasts. After four weeks of treatment, the effects of hPTH(1-34) on fracture healing showed no difference to those of GR(1-34). Consistently, GR(1-34) induced the similar osteogenesis but less osteoclastogenesis under the ex vivo condition immediately after administration compared to hPTH(1-34), which was verified by the weaker activation of RANKL, NFATC1, TRAP and Cathepsin K in GR(1-34) treatment. CONCLUSION: These results indicated that the PLC signaling activated by the intermittent injection of hPTH(1-34) leads to the bone resorption by rapidly activating the osteoclastogenesis in the fracture healing zone.

Effects of ulinastatin on inflammatory response and cognitive function after hip arthroplasty for the elderly patients with femoral neck fracture.

OBJECTIVE: To investigate the effects of ulinastatin on inflammatory response and cognitive function after hip arthroplasty for the elderly patients with femoral neck fracture. PATIENTS AND METHODS: A total of 80 patients with femoral neck fracture receiving hip arthroplasty in our hospital from August 2016 to February 2017 were selected and divided into observation group (n=40) and control group (n=40) using a random number table. The control group was treated with hip arthroplasty and symptomatic and supportive treatment after operation, while the observation group was treated with ulinastatin based on the treatment means of control group. The changes in antioxidant capacities, plasma noradrenaline (NA) and adrenaline (A) levels between the two groups before and after intervention were compared. The changes in neuron-specific enolase (NSE) and plasma S-100B protein levels before intervention and at 48 h after intervention were also compared. Moreover, the changes in mini-mental state examination (MMSE) scores during intervention and the Harris hip scores before intervention and at discharge between the two groups were compared. Finally, the off-bed walking time and postoperative discharge time of the two groups were recorded. RESULTS: After intervention, the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) and the total antioxidant capacity in observation group were significantly superior to those in observation group before intervention and control group after intervention (p<0.05). After intervention, the levels of NA and A in observation group were lower than those in control group (p<0.05), and the levels of interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (hs-CRP) in observation group were also lower than those in control group (p<0.05). At 48 h after intervention, the levels of NSE and plasma S-100B protein in observation group were significantly lower than those in observation group before intervention and control group at 48 h after intervention (p<0.05). At 12 h, 24 h and 48 h after intervention, the MMSE scores of observation group were superior to those of control group in the same period (p<0.05). After intervention, the Harris hip score of observation group was superior to that of control group before and after intervention (p<0.05). The postoperative discharge time of observation group was earlier than that of control group (p<0.05), and the off-bed walking time was also earlier than that of control group (p<0.05). CONCLUSIONS: The combined application of ulinastatin could effectively reduce the oxidative stress and inflammatory response, improve the neurological functions, and promote the postoperative recovery in the elderly patients with femoral neck fracture after hip arthroplasty.

Effect of metformin on ossification and inflammation of fibroblasts in ankylosing spondylitis: An in vitro study.

Ankylosing spondylitis (AS) is an autoimmune disease characterized by fibroblasts ossification. However, effective drug therapy for AS is lacking. As an antidiabetic drug, metformin has demonstrated an antiosteogenic effect on osteoblasts in vitro. And it is also a kind of specific agonists for adenosine 5'-monophosphate activated protein kinase (AMPK), which is blocked in the process of AS. Given the role in antiosteogenesis and AMPK activating, metformin was investigated of its effect on fibroblasts harvested from capsular ligament of patients with femoral neck fracture and AS. Osteogenic specific makers (Alp, Bglap, Runx2, Bmp2, and Col1) in fibroblasts administered with metformin (20 µg/mL) were detected by ALP staining, alizarin red staining, qPCR, and Western blotting after 7 and 14 days of culture. Inflammation genes (il1-ß and il6) and pathway (Pi3k, Akt, and Ampk) associated markers were also evaluated. Our results showed that osteogenic specific markers were greatly downregulated and ossification was effectively inhibited in AS fibroblasts after addition of metformin. Levels of inflammation markers were also decreased by metformin. Thus, metformin exerts potent effect on suppression of ossification and inflammation in AS fibroblasts via the activation of Pi3k/Akt and AMPK pathways, which may be developed as a potential agent for treatment of AS.

Low-energy atypical femoral shaft and ipsilateral neck fracture: a rare association.

This reports a case of a low-energy ipsilateral femoral shaft and neck fracture in a 69-year-old woman with vitamin D deficiency, who was taking long-term steroids and bisphosphonates. This is a fracture more commonly associated with a high-energy trauma. However, with an ageing global population and an increasing prevalence of bone insufficiency, we predict the incidence of this presentation to increase. Long-term bisphosphonate therapy has been associated with bone insufficiency and an increased rate of delayed union, adding to the complexity of management in these patients. There is currently no consensus regarding the choice of optimal implant or fixation technique to treat this challenging fracture pattern. We discuss the considerations that led to our management approach of a non-overlapping dynamic hip screw and femoral shaft plate construct which achieved uneventful bone healing and a good functional outcome within the first year of follow-up.

Can patients with femoral neck fracture benefit from preoperative thromboprophylaxis?: A prospective randomized controlled trial.

BACKGROUND: The effectiveness of preoperative thromboprophylaxis remains obscure in patients with femoral neck fracture. The purpose of the current study was to investigate whether these patients benefit from preoperative thromboprophylaxis. METHODS: In this prospective, randomized controlled trial, a total of 80 patients with femoral neck fracture were randomly assigned to receive either rivaroxaban or conservative treatment before surgery. For all patients, color Doppler ultrasound of both lower extremities was performed immediately after admission. The primary efficacy outcome was venous thromboembolism (VTE) defined as deep vein thrombosis (DVT) or pulmonary embolism (PE). The primary safety outcome was major bleeding. RESULT: Compared with conservative treatment, rivaroxaban could significantly reduce the incidence of DVT from 19.5% (8/41) to 2.6% (1/39) (P = .016). Preoperatively, there were a total of 9 occurrences of DVT including 8 DVT in the conservative treatment group and 1 in the oral rivaroxaban group. All cases of DVT were asymptomatic, with 8 of them diagnosed as isolated muscular calf vein thromboses. There were no differences between the 2 groups in terms of the overall incidence of major bleeding. CONCLUSION: Thromboprophylaxis with rivaroxaban prior to surgery can effectively reduce the risk of preoperative DVT for patients with femoral neck fracture without increasing the risk of bleeding.

Effect of bisphosphonate initiation at week 2 versus week 12 on short-term functional recovery after femoral neck fracture: a randomized controlled trial.

The appropriate time to initiate bisphosphonate treatment after a fragility fracture has not yet been established. In this study, we found no significant differences in short-term functional recovery between femoral neck fracture patients who received bisphosphonate treatment at 2 versus 12 weeks after hemiarthroplasty. INTRODUCTION: Bisphosphonate is the mainstay therapy for prevention and treatment of osteoporosis. The aim of this study was to investigate the effect of bisphosphonate initiation on short-term functional recovery in femoral neck fracture patients at 2 versus 12 weeks after hemiarthroplasty. METHODS: One hundred patients were randomly allocated into two groups in a parallel group designed, randomized, controlled trial. Both groups received risedronate 35 mg/week at either 2 or 12 weeks after hemiarthroplasty. All patients received calcium and vitamin D supplementation. Functional recovery was assessed by de Morton Mobility Index, Barthel Index, EuroQol 5D, visual analog scale, 2-min walk test, and timed get-up-and-go test at 2 weeks, 3 months, and 1 year after surgery. RESULTS: At the 3-month follow-up, all functional outcome measures showed significant improvement in both groups. There were no statistically significant differences in any of the functional outcomes between groups at both the 3-month and 1-year follow-ups. Although patients who received bisphosphonate initiation at week 2 had lower serum calcium level at 3 months and more overall adverse events than patients in the week 12 group, no patients in either group discontinued their prescribed medications. CONCLUSIONS: While underpowered, the findings of this study suggest that there were no significant differences in short-term functional recovery or significant adverse events between the two bisphosphonate groups. Thus, the initiation of bisphosphonate therapy may be considered as early as 2 weeks after femoral neck fracture. It is important that low serum calcium and vitamin D status must be corrected with calcium and vitamin D supplementation prior to or at the time of bisphosphonate initiation. CLINICAL TRIAL REGISTRATION NUMBER: This study was registered in the database via the Protocol Registration and Results System (PRS) (NCT02148848).

C1 Inhibitor Limits Organ Injury and Prolongs Survival in Swine Subjected to Battlefield Simulated Injury.

Complement system activation is recognized as a deleterious component of the mammalian physiological response to traumatic injury with severe hemorrhage (TH). Female Yorkshire swine were subjected to a simulated austere prehospital battlefield scenario. Each animal underwent controlled hemorrhage of 22 mL/kg at 100 mL/min rate for approximately 10 min followed by soft tissue injury, femur fracture, and spleen injury. Subsequent blood loss was uncontrolled. Twenty-eight minutes postinjury the animals were randomized into treatment or no treatment with recombinant human C1 esterase inhibitor (C1INH) (500 IU/kg, n = 11) and into receiving or not permissive hypotensive resuscitation (n = 14) with infusion of 45 mL/kg lactated Ringer's solution (2× blood lost). Observation and animal maintenance continued for 6 h at which time the animals had either expired or were euthanized. Heart, lung, and small intestine tissue samples were collected. Pharmacokinetic, hemodynamic, and metabolic parameters as well as survival time, plasma complement activity and tissue deposition, cytokine levels, and tissue injury were determined. We found that administration of C1INH protected tissues from damage, reduced the levels of inflammatory cytokines, and improved blood chemistry. Immunohistochemical analyses revealed that C1INH administration following TH markedly reduced complement activation and deposition in tissues. Importantly, C1INH administration prolonged survival of animals particularly in those which received resuscitation fluid infusion. Our data urge early administration of C1INH to limit organ damage and prolong survival of those injured in the battlefield.

Infections caused by Tissierella praeacuta: A report of two cases and literature review.

Herein we report two cases of infections caused by Tissierella praeacuta and a review of the literature. The first case was a septic pseudarthrosis of the left femur after multiple fractures. Two per-operative samples were positive with T. praeacuta. The patient was successfully treated by piperacillin - tazobactam and metronidazole. The second case was a bacteremia in a patient suffering from pyonephrosis and a hepatic abscess. The treatment was meropenem. No relapses were observed in both cases. Identification of the strains using MALDI-TOF coupled to mass spectrometry (MS) (Beckman coulter, France) was inconclusive in the two cases. Identification by 16S rRNA sequencing was then performed. This bacterium was susceptible to beta-lactams, chloramphenicol, rifampicine and metronidazole.

The role of platelet rich plasma in management of fracture neck femur: new insights.

PURPOSE: The aim of this study is evaluation of the efficacy of the use of platelet rich plasma (PRP) in management of femoral neck fractures. MATERIALS AND METHODS: This is a prospective study that was conducted between February 2010 and March 2013. A total of 60 patients were included in this study, categorized randomly into two groups. Group A included fracture neck femur treated by closed reduction and internal fixation with three cannulated screws and group B by addition of PRP to internal fixation. We planned to compare time of healing, need for revision and incidence of complications between the two groups. RESULTS: Union occurred in 53 patients (88.33 %) in both groups, 25 cases (83.3 %) in group A and 28 cases (93.3 %) in group B, including three cases (5 %) with avascular necrosis (AVN): two in group A (6.7 %) and one case in group B (3.3 %).Revision surgery was done for six cases (20 %) in group A and for two cases (6.7 %) in group B. In both groups, all united cases had good to excellent clinical outcome as regards Harris hip score (HHS) at the end of the follow up. CONCLUSION: Despite advances in surgical techniques and medical care, the risk of nonunion and avascular necrosis (AVN) after treatment of femoral neck fractures have not been changed appreciably in the last 50 years. Results of this study generally showed that both the median clinical and radiographic healing time were lower in group B compared to group A.

Audit improves emergency department triage, assessment, multi-modal analgesia and nerve block use in the management of pain in older people with neck of femur fracture.

BACKGROUND: The use of NBs as a mode of analgesia for #NOF in the ED is not common practice despite the reported clinical benefits of quicker onset of pain relief, decreased use of additional analgesia and decreased amounts of analgesia required when more than one mode of analgesia is prescribed. AIM: This study aims to test the hypothesis that the implementation of educational and awareness strategies increases knowledge, and implementation of the evidence based use of nerve blocks NB's, as a mode of analgesia for elderly patients with a fractured neck of femur (#NOF) in the Emergency Department (ED). METHODS: A retrospective clinical audit of medical records using explicit chart review pre and post implementation. RESULTS: Implementation of educational and awareness strategies on pain management to clinical staff in the ED resulted in a significant increase in the administration of NBs, use of multimodal analgesia, and a reduction in average milligrams of morphine administrated to elderly patients with #NOF. CONCLUSIONS: The number of older people with #NOF presenting to the ED in Australia is increasing and historically, pain management in this group of patients could be improved. This study demonstrated that an audit, intervention and re-audit design that focused on the implementation of educational and promotional strategies informed by evidence on current and best practice standards were successful in improving delivery of analgesia to elderly patients with #NOF in the ED.

The administration of intermittent parathyroid hormone affects functional recovery from pertrochanteric fractured neck of femur: a protocol for a prospective mixed method pilot study with randomisation of treatment allocation and blinded assessment (FRACTT).

INTRODUCTION: Pertrochanteric hip fractures occur in an elderly population and cause considerable morbidity and loss of functional ability as the fracture heals. Recently, parathyroid hormone (PTH), which is licensed for the treatment of osteoporosis, has been shown to potentially accelerate bone healing in animal and human studies. If its administration could allow a faster functional recovery after pertrochanteric hip fracture, then a patient's hospital stay may be reduced and rehabilitation could be potentially accelerated. PTH can currently only be administered by subcutaneous injection. The acceptability of this intervention is unknown in this elderly population. The aim of this pilot study is to inform the design of a future powered study comparing the functional recovery after pertrochanteric hip fracture in patients undergoing standard care versus those who undergo administration of subcutaneous injection of PTH. METHODS AND ANALYSIS: The study is an open label, prospective, randomised, comparative pilot study with blinded outcomes assessment to establish feasibility of the trial design. Patients will be randomised to receive a 6-week course of PTH or usual treatment. Functional outcomes will be assessed at 6 weeks and 12 weeks. Blinded assessment will be used to minimise the effect of bias of an open label study design. A nested qualitative study will investigate the patient experience of, and expectations following, hip fracture and the patient important aspects of recovery compared with the outcome measures proposed. RESULTS: Results will be analysed to establish the potential recruitment, compliance and retention rates using 95% CIs, and trial outcomes quoted with SDs and 95% CIs for the effect size. ETHICS AND DISSEMINATION: The study has been approved by the South West 2 Research Ethics committee (reference 10/H0206/34). The findings of this study will be disseminated to the medical community via presentations to orthopaedic, orthogeriatric and osteoporosis societies, and their relevant specialist journals. TRIAL REGISTRATION: ISRCTN Register reference number: ISRCTN03362357. Eudract Number: 2010-020081-22.