Study protocol: understanding the pathophysiologic mechanisms underlying delirium in older people undergoing hip fracture surgery.

BACKGROUND: Postoperative delirium (POD) is a common complication of older people undergoing hip fracture surgery, which negatively affects clinical- and healthcare-related outcomes. Unfortunately, POD pathophysiology is still largely unknown, despite previous studies showing that neuroinflammation, neuroendocrine dysfunction, increased reactive oxidative stress (ROS), and endothelial dysfunctions may be involved. There is also evidence that many of the pathophysiological mechanisms which are involved in delirium are involved in sarcopenia too. This article describes the protocol of a pilot study to evaluate the feasibility of a larger one that will explore the pathophysiological mechanisms correlating POD with sarcopenia. We will analyse whether various biomarkers reflecting neuroinflammation, ROS, neuroendocrine disorders, and microvasculature lesions will be simultaneously expressed in in the blood, cerebrospinal fluid (CSF), and muscles of patients developing POD. METHODS: Two centres will be involved in this study, each recruiting a convenient sample of ten older patients with hip fracture. All of them will undergo a baseline Comprehensive Geriatric Assessment, which will be used to construct a Rockwood-based Frailty Index (FI). Blood samples will be collected for each patient on the day of surgery and 1 day before. Additionally, CSF and muscle fragments will be taken and given to a biologist for subsequent analyses. The presence of POD will be assessed in each patient every morning until hospital discharge using the 4AT. Delirium subtypes and severity will be assessed using the Delirium Motor Subtype Scale-4 and the Delirium-O-Meter, respectively. We will also evaluate the patient's functional status at discharge, using the Cumulated Ambulation Score. DISCUSSION: This study will be the first to correlate biomarkers of blood, CSF, and muscle in older patients with hip fracture.

Clinical applications of Bioactive glass S53P4 in bone infections: a systematic review.

OBJECTIVE: Treatment of osteomyelitis, in of itself, is challenging but is further complicated by attendant bone infections. The management of bone infection, and bone rebuilding may be assisted by the use of bioactive glasses (BAGs) which have antimicrobial and osteo-stimulative proprieties. However, this clinical application and potential complications associated with BAGs (e.g., BAG S53P4), are poorly defined. The aim of this study is to review the results of clinical research using BAG S53P4 in the treatment of human bone infections. MATERIALS AND METHODS: This review was conducted in accordance with the PRISMA statement. The following databases were searched: PubMed, Cochrane Library, EMBASE, and Scopus. We examined electronic databases from 1965 to 2018 using different combinations of the following keywords: "S53P4", "BonAlive", "infection" and "osteomyelitis". RESULTS: Eight studies were considered which included a total of 276 cases (mean age of 49.3 years). The most frequent pathogen isolated was Staphylococcus aureus. A one-step surgical procedure was performed in 89.85% of cases. Good clinical and radiological outcomes were reported with a mean follow-up of 21.5 months. Twenty-three complications (8.3% of total cases) were described with the recurrence of bone infection as the most common complication (6.15% of total cases). CONCLUSIONS: BAG-S53P4 seems to be a useful bone filler in orthopaedic surgery for osteomyelitis treatment. The attendant clinical results and associated rate of complications associated with BAG S53P4 use are comparable with those of other techniques in the short term. However, long-term follow-up studies are required in order to confirm the longevity of this treatment.

Role of interleukin-10 in the synovial fluid of the anterior cruciate ligament injured knee.

OBJECTIVE: This review assesses the roles of IL-10 in post ACL reconstruction OA, and highlights the potential therapeutic effects of this cytokine. MATERIALS AND METHODS: We conducted a systematic review of the literature in order to consolidate evidence of IL10 profiles in synovial fluid (SF) of patients with ACL tears. The review was conducted in accordance with the PRISMA statement. In total, 10 studies were found to be pertinent and were considered in depth. Seven studies reported on trends in IL-10 concentrations after an ACL tear; in addition, three studies described IL-10 concentrations after ACL reconstruction. In all studies, IL-10 levels were assessed using enzyme-linked immunosorbent assay. RESULTS: IL-10 levels in SF were higher after ACL injury and ACL reconstruction compared to control knees. IL-10 levels were most elevated shortly after injury, but, decreased to more normal levels in chronic lesions. In contrast, the inflammatory cytokine TNF-α remained higher than controls immediately subsequent to, and, even 5 years post-injury. CONCLUSIONS: IL-10 is a modulatory cytokine with an active role in antagonizing TNF-α in the knee joint environment. Consideration of the role of IL-10 in the knee has now shifted from simply a key biomarker to having active therapeutic potential in the prevention of OA after ACL injury.

Phenotyping normal kidney function in elderly patients with type 2 diabetes: a cross-sectional multicentre study.

AIMS: Type 2 diabetes (T2D) accelerates the decline in glomerular function; however, some individuals do not develop chronic kidney disease despite advanced age and long-lasting T2D. We aimed to phenotype patients with T2D aged 80 years or older who presented with a fully preserved kidney function. METHODS: From an Italian population of 281,217 T2D outpatients, we collected data on demographics, anthropometrics, diabetes duration, HbA1c, fasting plasma glucose, lipids, liver enzymes, estimated glomerular filtration rate (eGFR), albumin excretion rate (AER), chronic complications, and medication use. We primarily compared patients with a fully preserved kidney function (eGFR > 90 ml/min/1.73 m2 and AER < 30 mg/24 h, or G1A1) with those with mild kidney impairment (eGFR 60-90 ml/min/1.73 m2 and AER < 30 mg/24 h, or G2A1). RESULTS: N = 113,860 had available data for eGFR and AER, 21,648 of whom were aged ≥ 80. G1A1 (n = 278) and G2A1 (n = 6647) patients represented 1.3 and 30.7% of aged T2D patients, respectively, with an average diabetes duration of 16 years. Differences between the G1A1 and G2A1 groups were entered in a multiple logistic regression analysis with and without imputation of missing data. After adjustment and in both imputed and non-imputed datasets, younger age, lower BMI and lower triglycerides were associated with fully preserved versus mildly impaired kidney function. The comparison between G1A1 and G1A2/3 yielded different results. CONCLUSIONS: In a rare population of patients with a fully preserved kidney function despite old age and long-lasting diabetes, lower BMI and triglycerides suggest that protection from lipotoxicity may preserve kidney function over time.

Paediatric radial neck fractures: One-step percutaneous reduction and fixation.

INTRODUCTION: Dislocated radial neck fractures of the third and fourth degree, according to the Judet classification, are rare events in children. These fractures account for 1% of all paediatric fractures. Their relatively low incidence is inversely proportional to the serious morphofuntional alterations that can follow without treatment. MATERIALS AND METHODS: Nine paediatric patients with an average age of 9.1 years (range 6-12 years), with radial neck fractures of the third and fourth degree, according to the Judet classification, were treated between 2010 and 2011. All patients underwent percutaneous reduction and fixation using only one K-wire by the same surgeon in a surgery time of 20 min (range 15-25 min). The average follow-up was 26.6 months (range 12-36 months), with X-rays and clinical evaluations conducted at four time points. The results were assessed radiologically (Métaizeau classification) and clinically (Mayo Clinic Elbow Performance Score). RESULTS: X-ray results (according to Métaizeau) were excellent in eight cases and good in one case. Clinical results were excellent in all cases. There was only one minor complication: a superficial skin infection that was treated with an oral antibiotic. DISCUSSION: The purpose of this study was to evaluate the results achieved in our hospital with a percutaneous reduction and fixation technique using only one K-wire in children with dislocated radial neck fractures of the third and fourth degree. The results obtained indicate that a single percutaneous surgery act that circumvents further operations is the best option for these patients. CONCLUSION: Although the number of patients in the study was small, the results are encouraging and support the continued use of this one-step percutaneous reduction and fixation technique.

The use of a preformed spacer in two-stage revision of infected hip arthroplasties.

Two-stage revision with the use of an antibiotic-loaded cement spacer has spread widely as a successful treatment for THA infection. Between 1999 and 2008, 28 patients with infected THA were treated with two-stage implant revision using a preformed spacer. The spacer was left in situ for 5.5 months (range 1-13 months), and the patients were allowed to walk with partial weight bearing. At a mean follow-up of 53 months (range 18-106 months), recurrence of infection was observed in only one patient. Complications were observed in five patients: three spacer dislocations, one distal femoral fracture occurred during stem removal, and one femoral artery pseudo-aneurysm. The mean HHS increased from 43 points (range 13-77) to 82 points (range 35-96). Though small prospective studies are reported in literature, good eradication rate and good functional outcomes encourage for the use of an antibiotic-loaded cement spacer. The industrial production ensures procedure standardization, well-defined physical and chemical properties to the device and eliminates time necessary to intraoperatory manufacturing.

The unstable total hip replacement.

BACKGROUND: Dislocation is one of the most common complications of total hip arthroplasty with a reported dislocation rate of 3.2%. Despite increased experience with hip replacement, the overall rate has not yet changed. The aim of this paper is to review the most recent literature published on this topic and indexed in Medline, in order to clarify the main risk factors, and to standardize a treatment protocol of such an important complication of prosthetic surgery. MATERIALS AND METHODS: Medline database was searched using key words: "hip dislocation", "hip instability" from 1980-2007. Studies were eligible for review and included if they met the following criteria: (1) publication in English, (2) clinical trials (3) review papers. RESULTS: The risk of first-time dislocation as a function of time after the surgery is not well understood. Most, but not all, series have demonstrated that the risk of dislocation is highest during the first few months after hip arthroplasty; however, first-time late dislocation can also occur many years after the procedure. Several risk factors were described, including the surgical approach, the diameter of the head, impingement, component malposition, insufficient abductor musculature. In addition, there are also many treatment options, such as long-term bracing after closed reduction, component reorientation, capsulorraphy, trochanteric advancement, increasing offset, exchange of the modular head and the polyethylene liner, insertion of constrained liner. CONCLUSION: Preventing hip dislocation is obviously the best strategy. Surgeons must take into account patient and surgical risk factors. For patients at high risk for dislocation the surgeon should accurately restore leg length and femoral offset; the use of larger femoral heads, posterior transosseous repair of the capsulotendinous envelope if posterior approach is chosen or the use of a lateral approach should be considered. Proper patient education and postoperative care are very important.

Endovascular repair of a pseudo-aneurysm of the common femoral artery after revision total hip arthroplasty.

Vascular injuries with acute arterial haemorrhage are rare but the infrequency of these complications may make their diagnosis and treatment challenging for surgeons unfamiliar with their management. In the past, surgery or coil embolisation has been used to treat these lesions; we describe the case of a pseudo-aneurysm of the common femoral artery developed during a total hip arthroplasty, promptly managed with an endovascular stent graft.

Popliteal artery pseudoaneurysm after a revision of total knee arthroplasty: endovascular treatment with a stent graft.

Injury to the popliteal artery during total knee arthroplasty is a very rare but dangerous complication. Several mechanisms are capable of generating a direct trauma to the vessel, like posterior retractor and oscillating saw. We report a case of popliteal artery pseudoaneurysm in a 52-year-old woman that occurred during revision of total knee arthroplasty, requiring emergency repair by means of percutaneous endovascular covered stenting.

"Conus" uncemented stem in developmental hip dysplasia.

The purpose of this study was to evaluate 115 "Conus" uncemented stems at an average follow-up of 6 years (2-9 years). Seventeen patients were lost at follow-up for a final number of 98 stems in 75 patients. The clinical outcome of 71 hips (72%) was graded excellent, 25 (25%) were good, one (2%) fair and one (2%) poor. The average Harris Hip Score increased from 49.35 before operation to 96.30 at the time of the last follow-up. None of the stems implanted required a revision for aseptic or septic loosening. Cortical hypertrophy or radiolucencies were never seen in any of the stems evaluated. Heterotopic ossification was seen in one hip (1%). Modification of the calcar was observed in 29 hips (30%) and they consisted in a slight rounding off of the proximal medial edge of the cut femoral neck. These results encourage the use of this versatile stem which showed a good primary and secondary stability, with a good load distribution along the femur.

Two-stage revision surgery to treat an infected hip implant. A comparison between a custom-made spacer and a pre-formed one.

A retrospective study was conducted to evaluate the results of two-stage surgical treatment for infected hip implant using two different spacers in antibiotic-impregnated cement, one custom-made and one pre-formed. Out of a total of 20 patients treated between 1995 and 2003, the temporary implant of one custom-made spacer was carried out in 8 cases, while in the remaining 12 cases we resorted to using a pre-formed spacer (Spacer G). In both groups we observed one recurrence of infection, for an overall 90% success rate in terms of eradication of the infection. Custom-made spacers had a greater incidence of local complications (1 breakage, 1 dislocation, 1 sinking of the revision stem) as compared to pre-formed ones (1 dislocation). The clinical results evaluated using the Harris Hip Score showed a statistically significant difference (p < 0.05) in both groups as compared to the preoperative score. The use of a pre-formed spacer, although more costly as compared to that custom-made one, was advantageous in some ways, for example in terms of standardization of the implant method, the lower incidence of mechanical complications and the better functional results.

Stem revision: special implant versus primary device.

The purpose of hip revision surgery is to relieve pain and restore hip function, while improving hip biomechanics and bone stock. The entity of bone stock impairment due to lysis indicates to the surgeon which revision stem he would preferably choose. Modern literature has described several options for stem revision, ranging from primary cemented/less implants in the case of limited proximal bone defects, to special revision stems where a massive femoral bone stock impairment is present. There are many classifications of the femoral bone-stock loss in the literature but most authors seem to agree that the treatment of minimal proximal defects should be performed with primary implant stems. The need to bridge a bigger bony gap makes distal fixation a good deal. Two options are described for this purpose: the Wagner stem and modular stems. Wagner's concept consists of a distal fixation based on the interference of the straight tapered titanium alloy stem at the level of the femoral isthmus, while longitudinal fins provide rotational stability. A wide variety of modular stems was lately developed to prevent major complication associated to the Wagner's stem, but some new problems arose from proximal overfill of the canal, difficult in assembly and fretting corrosion. Early experience with the new ZMR taper (Zimmer, Warsaw, IN, USA) modular revision stem is reported.

Peritalar release in the treatment of congenital talipes equinovarus clubfoot.

It is the purpose of this retrospective study to evaluate the results of the surgical treatment of congenital talipes equinovarus clubfoot. Seven patients affected with congenital talipes equinovarus clubfoot, 2 of which bilateral, treated surgically using peritalar release according to Simons were re-examined. The long-term follow-up results obtained after an average of 4 years were evaluated from clinical, morphofunctional, and radiographic points of view, and with the help of a photopodogram and computed baropodometry. The subjective satisfaction of the patients was also evaluated. Results were considered to be good in all of the cases. In conclusion, surgery involving peritalar release allows for correction of abduction of the forefoot, and restores physiological calcaneal valgus, re-balancing standing on the plantar surface; the persistence of an area of hypostanding in the forefoot operated on and of mild, residual cavus of the plantar arch do not, thus, seem to influence the good results obtained.

The relevance of hydroxyapatite and spongious titanium coatings in fixation of cementless stems. An experimental comparative study in rat femur employing histological and microangiographic techniques.

Pure titanium rods plasma-spray coated with hydroxyapatite (HA) or porous titanium (Ti) of controlled roughness were implanted bilaterally in the distal femur of Sprague-Dawley rats to compare the extent of bone growth on the two types of coating. The relevance of other factors, like mechanical stability and biological adaptation of the bone to the insertion of a foreign body implant, were investigated in femora which were over-reamed (absence of primary fit) or reamed without insertion of the rod. Continuous tetracycline labeling for the first 30 days and for the last 2 weeks in the 90-day group was performed; histological/histometric, fluorescence and microangiographic studies were carried out on serial sections of the implanted and control femora. In the group of stable implants, HA-coated rods showed 90% integration versus 53% with Ti-coated implants (P < 0.001); in over-reamed implants neither surface bone growth nor endosteal fixation occurred, and both types of rods were surrounded by a thick layer of connective tissue. The study documented early adhesion of osteoblasts and direct deposition of bone matrix on the substrate, while on spongious titanium osteogenesis was observed only in proximity to the surface. Remodeling of the reactive, primary bone to mature, lamellar bone took the form of a capsule surrounding the implants and radial bridges connecting the latter to the endosteal surface. The number, height and thickness of these bridges appeared to be the factors determining implant stability, rather than the extent of the bony capsule on the perimeter of the implant. Integration was a function not only of mechanical conditions and surface geometry, but also of the biological response of the whole bone to changes in the vascularization pattern. The reported phenomena can be seen more easily in experimental models involving small rodents because of their fast bone turnover and revascularization, but it is expected that they take place, even at a lower speed, in clinical situations like cementless stems of total hip replacement.

Isoelastic shoulder prostheses. Considerations on use and results.

The principles underlying the use of isoelastic shoulder prostheses are discussed and the results obtained in 8 patients are reported. Two operations were for pseudarthrosis of the humeral neck and 6 for osteolytic neoplasms. The results were assessed after an average follow-up of 4 years. Full movement was never recovered; there was partial recovery in 6 cases, and no significant recovery in 2. The extent of the surgical resection was determined by the type of lesion; in more conservative resections which allowed for the reconstruction of tendinous insertions, the functional results were better than in wide resections. The difficulty of recovering good movement was related to the limited possibilities of reconstructing the insertions of the external rotator muscles.

The role of mineralization in experimental models of osteogenetic induction with decalcified bone matrix.

The role of mineralization was studied in an experimental model of osteoinduction consisting of the implant of decalcified bone matrix in the rat muscle. After vascular connective tissue invasion of the matrix, the first phenomena is the appearance of hydroxyapatite crystals in the area of chondroid metaplasia from where the deposit of calcium-phosphate is extended to the surrounding decalcified matrix. The recalcified areas act as a substratum for the neo-osteogenesis. The appearances observed reproduced those of enchondral ossification, where the first osteoblasts differentiated on the calcified cartilaginous matrix and began to supply new bone matrix. Non-decalcified bone matrix implants were surrounded by a connective tissue capsule with features identical to those of a foreign body reaction and with total absence of vascular invasion. The absence of induction in this type of implant may be related either to masking of the osteoinducing protein in the calcified matrix, or to the absence of cells with osteogenic differentiation potential due to the lack of cellular invasion of the implant.