Survival of current production tumor endoprostheses: complications, functional results, and a comparative statistical analysis.

BACKGROUND AND OBJECTIVES: Retrospectively analyze outcomes of current-generation Global Modular Replacement System (GMRS) modular tumor endoprosthesis for the lower limb in primary and secondary implantation procedures. METHODS: Two hundred ninety five prostheses were implanted, 197 were primary implants, 98 were for revision surgery; revision procedures included 84 failed tumor reconstructions and 14 failed non-tumor reconstructions. Anatomic sites included: distal femur 199; proximal tibia 60; proximal femur 32;total femur 4. Endoprosthesis failures were classified as soft-tissue failures (Type 1), aseptic loosening (Type 2), structural fracture (Type 3), infection (Type 4), and tumor recurrence (Type 5). MSTS functional scores were measured. RESULTS: The overall failure rate was 28.8% and failure occurred at a median of 1.7 years (range, 1 month to 7 years). At a mean oncologic follow up of 4.2 years (range, 2-8 years), 195 patients are continuously NED, 43 NED after treatment of relapse, 10 AWD, 33 DWD. There was a significant difference in implant survival of all modes of failure between primary and revision implants (P = 0.03). No prosthetic fracture occurred. The average functional score was 81.6% (24.5). CONCLUSIONS: Mid-term results with GMRS are promising, with good functional results and low incidence of complications for primary implants. LEVEL OF EVIDENCE: Therapeutic study, level IV-1 (case series).

COVID-19 strategy in organizing and planning orthopedic surgery in a major orthopedic referral center in an area of Italy severely affected by the pandemic: experience of the Department of Orthopedics, University of Padova.

BACKGROUND: According to the required reorganization of all hospital activities, the recent COVID-19 pandemic had dramatic consequences on the orthopedic world. We think that informing the orthopedic community about the strategy that we adopted both in our hospital and in our Department of Orthopedics could be useful, particularly for those who are facing the pandemic later than Italy. METHODS: Changes were done in our hospital by medical direction to reallocate resources to COVID-19 patients. In the Orthopedic Department, a decrease in the number of beds and surgical activity was stabilized. Since March 13, it has been avoided to perform elective surgery, and since March 16, non-urgent outpatient consultations were abolished. This activity reduction was associated with careful evaluation of staff and patients: extensive periodical swab testing of all healthcare staff and swab testing of all surgical patients were applied. RESULTS: These restrictions determined an overall reduction of all our surgical activities of 30% compared to 2019. We also had a reduction in outpatient clinic activities and admissions to the orthopedic emergency unit. Extensive swab testing has proven successful: of more than 160 people tested in our building, only three COVID-19 positives were found, and of over more than 200 surgical procedures, only two positive patients were found. CONCLUSIONS: Extensive swab test of all people (even if asymptomatic) and proactive tracing and quarantining of potential COVID-19 positive patients may diminish the virus spread.

Infection in orthopaedic oncology: crucial problem in modern reconstructive techniques.

OBJECTIVE: Infection after orthopaedic oncology surgery is a relatively frequent complication. Infection rate ranges in the literature between 3.7% and 19.9%, increasing up to 47% after pelvic resection and reconstruction. It represents a challenging topic when occurring in oncologic patients because of the delay of systemic and local treatments, influencing prognosis. Infection is a major concern in terms of both prevention and treatment. The aim of our review was to analyze data reported in the literature about strategies and new materials for infection prevention in musculoskeletal oncology surgery. MATERIALS AND METHODS: We reviewed the literature focusing on the use of new materials that can reduce the risk of infection, avoiding biofilm formation on the implant surface. RESULTS AND DISCUSSION: New materials are available to try to reduce the risk of infection. Iodine-coating, DAC-coating or silver-coating, are the more promising technologies available at today. Initial results with DAC-coating in non-oncological patients are interesting; however, studies about its efficacy in preventing infection in orthopaedic oncology are not present in literature. On the other side, iodine-coating implants or silver-coating prostheses demonstrated efficacy against early infections, associated with lower risk of implant removal and amputation as final surgery. CONCLUSIONS: Post-operative infections in orthopaedic oncology surgery are still frequent, and their diagnosis and treatment are demanding. According to the literature, silver-coated prostheses should be considered as the best option in case of revision surgery due to infection. However, there is no evidence that these new materials are effective to decrease the risk of infection drastically. Further studies with numerous series and long-term follow up are required.

Megaprosthesis of the knee in tumor and revision surgery.

The introduction of multidisciplinary approach with chemo and radiotherapy, the advances in surgical and the improvements of diagnostic techniques allowed limb salvage surgery in most cases of bone sarcomas instead of amputation. Modular megaprostheses are the most common method of reconstruction after segmental resection of the long bones in the extremities for their availability, immediate fixation, early weight bearing, good function. Despite the advances in materials and implant designs, these systems have an high incidence of complications. Aim of this study was to report the experience on mega-prostheses implanted around the knee in tumor and revision surgery to analyze: the most frequent used current systems, the problems of stems fixation, extensor mechanism reconstructions in proximal tibia resections and the preservation of growth of the lower extremity in children.

Fatty acid dietary intake and the risk of ischaemic stroke: a multicentre case-control study. UFA Study Group.

A low dietary intake of unsaturated fatty acids has been found in male patients with stroke as compared with controls in Italy, and a high consumption of meat has been associated with an increased risk of stroke in Australia. We present a case-control study, comparing the unsaturated and saturated fatty acids content of red cell membranes (which reflects the dietary intake of saturated and unsaturated fats) in 89 patients with ischaemic stroke and 89 controls matched for age and sex. In univariate analysis, besides hypertension, atrial fibrillation, ischaemic changes in ECG and hypercholesterolaemia, stroke patients showed a lower level of oleic acid (P = 0.000), but a higher level of eicosatrienoic acid (P = 0.009). Conditional logistic regression (dependent variable; being a case) showed that the best model included atrial fibrillation, hypertension, oleic acid and eicosatrienoic acids. These results confirm a possible protective role of unsaturated fatty acids against vascular diseases; however, we did not find any difference in the content of omega3 acids, which have been considered in the past to protect against coronary heart disease. We conclude that the preceding diet of patients with ischaemic stroke may be poor in unsaturated fatty acids (namely, oleic acid), and this defect is independent of other vascular risk factors. Only further studies will show whether changes in diet and/or supplement of unsaturated fatty acids might reduce the incidence of ischaemic stroke.

Biochemical studies on the nootropic drug, oxiracetam, in brain.

The aim of this work was to study the effects of the nootropic drug oxiracetam, on lipid metabolism in rat brain. Twenty-month-old rats and spontaneous hypertensive (SHR) rats with cerebrovascular lesions were used, which showed an impaired learning and memory rate if challenged with behavioral tests. Oxiracetam improves the in vitro and in vivo synthesis of phosphatidylcholine (PhC) and phosphatidylethanolamine (PhE) impaired by aging, when respectively added to the incubation medium or administered subacutely to animals. SHR rats drinking saline, and with cerebrovascular lesions, have a reduced choline incorporation into cerebral phospholipids and an increase of arachidonic acid release from the same lipids if compared to SHR rats (without cerebrovascular lesions) drinking water. They also show a decreased incorporation rate of arachidonic acid into PhC, PhE, and PhC plasmalogen and PhE plasmalogen. If oxiracetam is chronically administered (200 mg/kg/day for 14 weeks) a significant variation in the incorporation of both precursors takes place. In the first 2 h after the intracerebroventricular (i.c.v.) injection of choline and arachidonic acid the values are comparable to those observed in SHR rats with lesions; at longer time intervals, however, the rates of incorporation are similar and even better than those of SHR rats without lesions. Since the drug does not seem to influence the incorporation of the precursors in the first 2 h after their administration, we may assume that oxiracetam acts on the turnover of the phospholipids more than on their rate of synthesis from injected precursors.

Membrane-bound base-exchange reactions in animal tissues.

The calcium-stimulated incorporation of ethanolamine, L-serine and choline into rabbit synaptosomal phospholipids in vitro has been investigated. The synaptosomal membranes were prelabelled in vitro in their choline-, ethanolamine- or serine-phosphoglycerides by base-exchange and then chasing experiments were performed by displacing the lipid-bound base by ethanolamine, choline or L-serine labelled with a different isotope. The results indicate that membrane phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine are substrates for the exchange with all the three mentioned bases. A very small phospholipid pool (0.5-2% of the total available pool) is active in the calcium-dependent exchange between membrane phosphatidylcholine or phosphatidylethanolamine and free bases, whereas the pool of exchanging phosphatidylserine is sensibly larger (2-9%). In another series of experiments the effect of the base-exchange reaction upon the production of cyclic-AMP at the level of rat brain synaptic membranes has been examined. An exchange with ethanolamine produces a significant decrease of the NaF-stimulated production of the cyclic nucleotide, whereas it increases the noradrenaline-induced production. With some exceptions, the exchange with L-serine produces opposite effects. The possible physiological importance of phospholipid pool at the synaptosomal level is discussed.

Relationships between base-exchange reaction and synaptosomal phospholipid pool in the rabbit brain in vitro.

The calcium-stimulated incorporation of ethanolamine, L-serine and choline into rabbit synaptosomal phospholipids in vitro has been investigated. The synaptosomal membranes were prelabelled in vitro in their choline-, ethanolamine- or serine-phosphoglycerides by base-exchange and then chasing experiments were performed by displacing the lipid-bound base by ethanolamine, choline of L-serine labelled with a different isotope. The results indicate that membrane phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine are substrates for the exchange with all the three mentioned bases. A very small phospholipid pool (0.5-2% of the total available pool) is active in the calcium-dependent exchange between membrane phosphatidylcholine or phosphatidylethanolamine and free bases, whereas the pool of exchanging phosphatidylserine molecules is sensibly larger (2-9%). The possible physiological importance of these small phospholipid pools, involved in base-exchange reaction at brain membrane level, is discussed.

Phospholipid base-exchange in brain microvessels.

The capillary endothelium of cerebral microvessels plays an important role in homeostasis within the central nervous system. The flux of fluids and solutes takes place through the lipid matrix of plasma membranes and the maintenance of their structural composition is necessary for cell membrane permeability and the cellular transport systems. Few studies have been carried out to clarify the relationships between brain microvessel lipid metabolism and the role of this metabolism. We have studied a particular aspect of the phospholipid metabolism, i.e. their hydrosoluble head group exchange with free choline, ethanolamine or serine, in capillaries from brains of both 4 month- old and 24 month-old rats. The results obtained indicate that microvessels possess the biochemical machinery of base-exchange reaction, whose activity rate appears unaffected by age.

Effect of age and strain on cerebral phospholipid metabolism.

It has been demonstrated that spontaneously hypertensive adult rats (SHR) develop severe hypertension and cerebrovascular lesions on drinking 1% NaCl from weaning. Phospholipid metabolism is actively altered in these severely lesioned animals (SHR-NaCl) as compared to SHRs which drink only water and showed only sporadic cerebrovascular lesions. We have tested the incorporation of water soluble phospholipid precursors into the corresponding phospholipid from different brain areas, by injecting either a mixture of labeled glycerol and choline or glycerol and ethanolamine into the lateral ventricle of the brain of adult (4 months old) and senescent (12 months old) SHR-NaCl. The results were compared to those obtained from 4 and 12 months old Wistar normotensive rats. When adult normotensive rats were compared with adult hypertensive rats (4-SHR-NaCl) incorporation was found to decrease in some areas according to the precursors injected. Similar results were obtained from 12 month old normotensive Wistar rats that, however, showed a decrease in phospholipid biosynthesis in all the area tested. Interestingly, no significant differences of incorporation rate were found between 12 month old normotensive and 12 month old hypertensive rats.

Linoleic acid metabolism in brain cortex of aged rats.

The linoleic acid metabolism was examined in the brain cortex of 4 month-old and 24 month-old rats. After the injection of [1-14C]-linoleate into the lateral ventricle of the brain the animals were sacrificed at 1,3 and 6 hours from the injection. The linoleate (18:2) incorporation into lipids, the presence of fatty acid peroxidation products, as well as the 18:2 transformation into elongated and desaturated derivatives were determined. Both an age-related reduction in linoleate incorporation rate into glycerophospholipids and a decrease in fatty acid turnover were found. Furthermore, in glycerophospholipids from 24 month-old rat brain cortex a higher level of hydroperoxide derivative of linoleate was found as compared to 4 month-old animals, and this damaged fatty acid is eliminated more slowly in aged rats than in adults. Finally, unlike 4 month-old animals, a stimulation of the transformation rate of linoleate into desaturation (6,9,12-C18:3) and elongation (8,11,14,C20:3) products was found in 24 month-old rat brain cortex. On the contrary, as far as arachidonic acid (one of the most important end products of the mechanism of linoleate modification) is concerned, the differences between aged and control animals were small, making it quite difficult to attribute a physiological meaning to this phenomenon.

The effect of transient ischemia on fatty acid and lipid metabolism in the gerbil brain.

Brain ischemia was produced in gerbils by contemporary occlusion of both carotid arteries. Definite changes of the energy state in brain demonstrated that carotid occlusion was effective. At short time intervals from occlusion the free fatty acid content, their distribution, and their concentration and specific activity in arachidonate were determined in brain. A noticeable increase of the arachidonate pool and that of other free fatty acids was detected at very early times from occlusion. Specific activity by arachidonate increased after 30-60 seconds from ligation. By examining arachidonate distribution and specific activity in neutral and polar lipids of brain, it is concluded that phosphatidylcholine and phosphatidylinositol represent the more important source for the release of arachidonate during ischemia. Enzymic-mediated phenomena produced free arachidonate from lipids by a mechanism yielding diglycerides further transformed into fatty acids and by lipid degradation through phospholipase A activity.

The influence of CDP-choline on brain lipid metabolism during ischemia.

The intraperitoneal administration of CDP-choline to gerbils (Meriones unguiculatus) partially prevented the changes of lipid metabolism found in brain after ischemia due to carotid occlusion. The increase of diglyceride pool and of its content of radioactivity, due to arachidonate labelling, was almost completely corrected by the treatment. The increase of the free fatty acids, due to ischemia, was unaltered. The decrease of the phosphatidylcholine labelling due to ischemia was partially corrected by the administered CDP-choline.

Abnormalities of the erythrocyte membrane phospholipids in Friedreich's ataxia.

The phospholipid composition and the fatty acids of the phospholipids in the erythrocyte membranes were studied in 5 patients with Friedreich's ataxia. The sphingomyelin content was found to be insignificantly reduced, that of phophatidylethanolamine was, on the contrary, increased even if non-significantly. The linoleic acid content was significantly decreased both in the total fraction of the phospholipids and in the isolated phosphatidylcholine. The relationship between the phospholipid composition and the structure and function of the membrane are discussed.

The effect of cytidine-diphosphate choline (CDP-choline) on brain lipid changes during aging.

Lipid synthesis has been tested in vivo in different brain areas of 12-month-old male rats. Cortex, striatum, brainstem, and subcortex of brain have been examined. The cerebellum was discarded. Mixtures of (2-3H)glycerol and (Me-14C)choline were injected into the lateral ventricle of the brain as lipid precursors, and their incorporation into total lipid, water-soluble intermediates and choline-containing phospholipids was examined 1 hr after isotope injection. In another series of experiments cytidine-5'-diphosphate choline (CDP-choline) was injected intraventricularly to the aged rats 10 min before sacrifice with a simultaneous injection, and radioactivity assays were performed as above. Distribution of radioactivity content of CDP-choline among brain areas 10 min after its administration showed a noticeable enrichment of the nucleotide and water-soluble-related compounds in the examined areas, but to a lesser degree in the cerebral cortex. The incorporation of labelled glycerol, which is severely depressed in aged rats in all four areas [Gaiti et al, 1982, 1983], was increased only in the cortex, and apparently decreased in the other areas. This last result is probably due to a dilution effect brought about by the administered cold CDP-choline upon the (14C)-containing water-soluble metabolites. As a consequence, the (3H)/(14C) ratio in total lipid and in isolated phosphatidylcholine and choline plasmalogen increased after CDP-choline treatment.

The influence of cytidine on the endogenous pool of CDP-choline, CDP-ethanolamine, and CMP of the rat brain.

Cold cytidine was intraventricularly administered into the brain of young rats, and its effect on CDP-choline, CDP-ethanolamine, and CMP pools followed for different time intervals and with various amounts of administered cytidine. The injected nucleoside produces a measureable increase of th concentrations of all three nucleotides. The increase produced by injecting 2.5 mumol of cytidine for brain does not essentially change with higher doses of injected nucleoside, except for CMP, whose increase reaches a maximum with 5 mumol of cytidine. A clear time dependence on cytidine administration was shown. The increases of the three nucleotide concentrations do not show a maximum till 60 min from administration into CMP and CDP-bases and measurably increases their endogenous brain pools. The compound is likely to enter metabolic events connected with phospholipid metabolism in brain.

Arachidonic and palmitic acid utilization in aged rat brain areas.

We have previously demonstrated that the arachidonic acid (20:4) incorporation into brain lipids differs according to the age of the animals used and the experimental conditions adopted. These differences led to a further investigation of arachidonic acid uptake in both aged and adult rat brains, its transformation into CoA derivatives, its incorporation into diacyl-glycerols and polar lipids, and finally its oxidation to CO2. These metabolic parameters were then compared with those obtained after using the saturated fatty acid palmitate (16:0). In both cases slices or mitochondria from different brain areas of 24-month-old and 4-month-old rats were examined. The results obtained indicate that the uptake of the fatty acids into cells is not modified by age. However, the successive metabolic transformations of the acids are altered to a considerable extent. In particular, in 24-month-old animals (compared with 4-month-old rats) there is a significant decrease of 20:4 in its incorporation into lipids as well as its oxidation to CO2, while arachidonoyl-CoA content increases by about 50%. This increased amount of CoA derivative, which has a potent detergent effect, may interfere with membrane structure and affect membrane physiological functions. Furthermore, because the free arachidonate pool is maintained in a dynamic equilibrium with its esterified forms, the final result may be a perturbation of this equilibrium.

Synaptosomal phospholipid pool in rabbit brain and its effect on GABA uptake.

Rabbit synaptosomes have been used to study the effect of the base-exchange reaction in membrane phospholipids on gamma-aminobutyric acid (GABA) transport in vitro. The uptake of GABA was measured after a base-exchange reaction with ethanolamine, choline, or L-serine and after subsequent displacement of these exchanged moieties from lipid by bases of similar or different structures which were added to the synaptosomal medium. Serine incorporation stimulated GABA transport, but its displacement from membrane lipid by choline or ethanolamine induced an inhibition of GABA transport. Ethanolamine incorporation inhibited GABA transport, but its displacement of serine or choline resulted in stimulation of GABA uptake. Choline incorporation also inhibited GABA transport, although less than ethanolamine. The pool size of synaptosomal phospholipids, presumably involved in GABA uptake, accounted for 0.2 to 10% of the total content of membrane phospholipid. Thus, alteration of phospholipid composition by exchange of the lipid hydrophilic head-groups influences the extent of GABA uptake into rabbit synaptosomes.