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.

Distal humeral septic non-union treated with debridement and vascularized fibular transfer: case report and review of the literature.

Clinical management of a septic non-union of the distal humerus is challenging and is complicated by the diversity of potential treatments which are variably successful. We report a novel and very successful treatment of a 58-year-old man presenting an infected non-union of the right distal humerus, secondary to a closed fracture initially treated with two anatomic plates. After hardware removal, a two-stage reconstruction was performed. Bone and soft-tissue debridement was performed, followed by vascularized fibular transfer and free iliac bone crest chips fixed with plates and screws. Consolidation was achieved within three months, and a very good elbow function was presented two years thereafter. This technique shows great promise for improved management of large segmental infected bone defects of complete articular distal humeral fractures, above many currently recognized treatments.

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.

Rationale and design of the DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes): A multicenter retrospective nationwide Italian study and crowdsourcing opportunity.

BACKGROUND: Randomized controlled trials (RCTs) in the field of diabetes have limitations inherent to the fact that design, setting, and patient characteristics may be poorly transferrable to clinical practice. Thus, evidence from studies using routinely accumulated clinical data are increasingly valued. AIMS: We herein describe rationale and design of the DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes), a multicenter retrospective nationwide study conducted at 50 specialist outpatient clinics in Italy and promoted by the Italian Diabetes Society. DATA SYNTHESIS: The primary objective of the study is to describe the baseline clinical characteristics (particularly HbA1c) of patients initiated on dapagliflozin from marketing authorization approval to the end of 2016. Secondary and exploratory objectives will evaluate the changes in glycaemic and extraglycaemic efficacy parameters after initiation of dapagliflozin or after initiation of comparator glucose lowering medications (DPP-4 inhibitors, gliclazide extended release, and long-acting GLP-1 receptor agonists). An automated software will extract relevant data from the same electronic chart system at all centres, thereby minimizing data treatment and human intervention. CONCLUSION: The study is expected to collect an enormous dataset of information on dapagliflozin- and comparator-using patients. After study completion, the Italian Diabetes Society will launch an open crowdsourcing call on the DARWIN-T2D database, challenging diabetes researchers to apply their ideas and approaches to address new unmet needs and knowledge gaps in diabetes. We believe this will move DARWIN-T2D to the next generation of real world studies.

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.

Osseointegration in the elderly.

Osseointegration is a term that refers to the formation of a direct interface between an implant and bone without intervening soft tissue. Cementless femoral fixation in total hip arthroplasty is dependent on mechanical and biological factors that affect implant stability and long-term outcome. Osteoporosis leads to morphological and biological alterations in the proximal femur that adversely affect both mechanical stability of implant and biological response of bone, making it more challenging to achieve a valid osseointegration.

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.

Analysis of bone ingrowth on a tantalum cup.

BACKGROUND: Trabecular Metal (TM) is a new highly porous material made of tantalum (Zimmer, Warsaw, Indiana, USA). Its three-dimensional structure is composed of a series of interconnected dodecahedron pores that are on average 550 microm in diameter. This size is considered optimal for bone ingrowth and is similar to trabecular bone. The elastic modulus of TM (3 GPa) is more similar to that of cancellous (0,1-1,5 GPa) or cortical (112-18 GPa) bone and is significantly less similar to that of Titanium (110 GPa) and Co-Cr alloys (220 GPa). These features enable bone apposition and remodeling. The purpose of the present study was to evaluate the histology of the bone-implant interface in a human specimen. MATERIALS AND METHODS: A highly porous tantalum cup (Zimmer, Warsaw, Indiana, USA) was removed for recurrent dislocations three years after implantation. In order to obtain a slice of the cup, two cuts were made on the centre using an Exakt cutting machine. Then the slice was embedded in a Technovit resin and a Hematoxylin-eosin stain was used to study the bone tissue. Bone ingrowth was calculated using a method based on simple calculations of planar geometry. RESULTS: The histological evaluation of the periprosthetic tissues revealed a typical chronic inflammation with few particles of polyethylene that were birefringent using polarized light. The quantitative evaluation of bone ingrowth revealed that more than 95% of voids were filled with bone. DISCUSSION: In the literature, a lot of studies focused on tantalum were carried on animal model. Up to now little information is available about the histology of the bone-tantalum interface in a human artificial joint. We had an opportunity to remove a well integrated cup hence this study. The histology confirmed the strong relationship between the structure of this material and bone. The morphometric analysis revealed a high percentage of bone ingrowth.

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.

Femoral revision with special stems.

None.

The surgical treatment of supracondylar fractures of the humerus in children by percutaneous fixation using Kirschner wires: analysis of residual deformities.

The authors report the results of the surgical treatment of supracondylar fractures of the humerus during childhood by closed reduction and percutaneous synthesis using Kirschner wires. A total of 16 patients were considered, who were re-examined at a mean follow-up of 57.9 months (24-84). The fractures were evaluated according to the Gartland classification modified by Wilkins. The results were classified based on Flynn criteria, and the duration of hospitalization and early and late complications such as neurovascular deficit and residual deformities were also taken into consideration. Final results were satisfactory in 94% of cases with no septic, vascular, or nervous complications. We observed remodeling of three fractures with defect in reduction of the distal fragment on a sagittal plane, and the absence of correction in a case of deficit in reduction on the frontal plane. Deformity persisted with no secondary displacement in 5 cases with correct postoperative reduction.

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.