Kinematic versus mechanical alignment in total knee arthroplasty: a preliminary study.

Despite the great advances of the technology in the joint prosthesis and the high execution rate of total knee arthroplasty (TKA), there are still about 15% of clinical unsatisfactory rate in this surgery. TKAs are currently performed using a mechanical alignment of the knee, correcting varus/valgus deformities with the purpose to achieve a longer implant survivorship, but this surgical technique results in an alteration of the normal knee kinematics. Nowadays, the idea to restore the pre-arthritic alignment of the knee with the goal to obtain a normal kinematics and better functional results becomes more and more consistent and the kinematic alignment (KA) was developed as alternative to the mechanical one. The aim of this preliminary study is to analyse the functional outcomes in patients who underwent KA-TKA in the short-term follow-up and to compare them with those obtained in patients treated by the mechanical alignment (MA) TKA. Therefore, skeletally mature patients, with no history of previous knee surgical procedures, who underwent isolated TKA for knee osteoarthritis, were included in this study. The patients were prospectively divided into two homogeneous groups according to the different surgical techniques performed (KA-TKA and MA-TKA groups). Clinical and functional scores (VAS, KOOS-PS, MCS-12, Final KSS, and Functional KSS) were collected pre- and postoperatively at a mean follow-up of 3 three months. As a result, 26 patients were included in the study, with a mean age of 69.3±7.61 years old (range: 55 - 84 years old). There were 38.5% male and 61.5% female. There were 13 patients in KA-TKA and 13 patients in MA-TKA. Three months after surgery each of the scores tested demonstrated statistically significant better outcomes in KA-TKA, compared to the MA-TKA group. MCS-12 resulted comparable in the two study groups. This preliminary study compares the short-term clinical and functional outcomes between KA and MA in total knee replacement. Further studies are required to confirm these results and to extend the sample size to obtain reliable clinical evidences.

Comparison of early functional outcomes between two different surgical approaches for total hip arthroplasty.

Total Hip Arthroplasty (THA) is considered the most successful treatment for advanced hip osteoarthritis. Different surgical approaches for THA are available and they have shown excellent outcomes in the long-term follow-ups. However, few studies have analyzed the functional outcomes in the first days after a THA surgery. The purpose of this study was to compare the early functional outcomes between two different surgical techniques: a minimally invasive direct anterior approach (mini-DAA) and a postero-lateral approach (PL). Twelve patients for each group were analyzed. Pre- and postoperative (3, 10, 30 and 90 days after surgery) Patient-Reported Outcome Measures (PROMs) were administered: HOOS, HHS, VAS and SF-12-v2 scores. Moreover, comparison between surgical operation time and blood loss were examined. PROMs showed a significant improvement in the SF-12-v2 in the mini-DAA group compared to the PL group at 3 days after surgery: this difference was maintained also after 10 and 30 days. In addition, HOOS and HHS were significantly ameliorated in the mini-DAA group starting 10 days from surgery. In both groups, a physiological pain reduction was observed in the first days after surgery; comparing it to the pre-surgical VAS values, we found a significant improvement in the scores for the mini-DAA group after 30 days. Moreover, we demonstrated a significant reduction in blood loss for the mini-DAA group. Surgical operation times were similar in the two groups; however, the duration of the mini-DAA procedure was shorter compared with the known literature. In this preliminary study, we demonstrated that the minimally invasive direct anterior approach for THA may lead to benefits in the early postoperative time, as it allows for an improvement in functional outcomes, a reduction of postoperative pain, a reduction of hospitalization time and consequent reduction of postoperative complications; therefore, this surgical approach may consent an early return to work and daily activities.

Evaluation of the use of autologous micro-fragmented adipose tissue in the treatment of knee osteoarthritis: preliminary results of a randomized controlled trial.

Articular cartilage injuries are still unsolved due to the limited intrinsic healing potential of this tissue. Unlike other tissues, inflammation in the synovial joint causes perpetual damage and progressively leads to the development of osteoarthritis. Previous in vitro and in vivo studies have demonstrated the efficacy of mesenchymal stem cells isolated from adipose tissue in modulating inflammation. In this study, we analyzed the role of these cells in modifying the pathological microenvironment present in knee osteoarthritis. This is an interventional, prospective, randomized, controlled study. Starting from June 2017, 39 patients with grade III and IV knee osteoarthritis of Kellgren-Lawrence were enrolled, aged between 45 and 75 years, with pain greater than or equal to 6 according to the VAS scale, without ligament instability, with an axial deviation not greater than 10° and with a BMI between 18 and 30. The control group underwent an arthroscopic debridement, while the experimental group underwent an arthroscopic debridement and a subsequent intra-articular injection of autologous micro-fragmented adipose tissue. Patients were evaluated before surgery and at 6 months after the procedure, by radiological analysis (MRI) and functional outcome measures. The main purpose of the study is to evaluate the symptomatic improvement by comparing the functional outcome scores between the two groups. At 6 months after treatment, preliminary results on 39 patients showed pain reduction and functional improvements in the experimental group without a significant difference due to the low number of patients. The radiological and biochemical analyses are still ongoing. To date, the study has not revealed any side effects. These preliminary results demonstrate an encouraging positive trend in the experimental group. Patient recruitment is still ongoing to finalize the statistical analyses and to confirm our hypothesis.

Quality indicators in headache care: an implementation study in six Italian specialist-care centres.

BACKGROUND: Headache disorders are highly prevalent, and have a substantial and negative impact on health worldwide. They are largely treatable, but differences in structure, objectives, organization and delivery affect the quality of headache care. In order to recognize and remedy deficiencies in care, the Global Campaign against Headache, in collaboration with the European Headache Federation, recently developed a set of quality indicators for headache services. These require further assessment to demonstrate fitness for purpose. This is their first implementation to evaluate quality in headache care as a multicentre national study. METHODS: Between September and December 2016, we applied the quality indicators in six Italian specialist headache centres (Bologna, Firenze, Modena, Padova, Roma Campus Bio-Medico and Roma Sapienza). We used five previously developed assessment instruments, translated into Italian according to Lifting The Burden's translation protocol for hybrid documents. We took data from 360 consecutive patients (60 per centre) by questionnaire and from their medical records, and by different questionnaires from their health-care providers (HCPs), including physicians, nurses, psychologists and nursing assistants. RESULTS: The findings, comparable between centres, confirmed the feasibility and practicability of using the quality indicators in Italian specialist headache centres. The questionnaires were easily understood by HCPs and patients, and were not unduly time-consuming. Diagnoses were almost all (> 97%) according to ICHD criteria, and routinely (100%) reviewed during follow-up. Diagnostic diaries were regularly used by 96% of physicians. Referral pathways from primary to specialist care existed in five of the six clinics, as did urgent referral pathways. Instruments to assess disability and quality of life were not used regularly, a deficiency that needs to be addressed. CONCLUSION: This Italy-wide survey confirmed in six specialist centres that the headache service quality indicators are fit for purpose. By establishing majority practice, identifying commonalities and detecting deficits as a guide to quality improvement, the quality indicators may be used to set benchmarks for quality assessment. The next step is extend use and evaluation of the indicators into non-specialist care.

Apoptotic cells overexpress vinculin and induce vinculin-specific cytotoxic T-cell cross-priming.

Here we show that apoptotic cells overexpress vinculin and are ingested by dendritic cells, which subsequently cross-prime vinculin-specific cytotoxic T lymphocytes (CTLs). Successful cross-priming requires that the apoptotic cells provide maturation signals to dendritic cells through CD40-CD40 ligand (CD40L) interactions. If apoptotic cells are CD40L-, the help of a third T cell is needed for priming, indicating a regulatory role for apoptotic cells in determining priming or tolerance. Vinculin-specific CTL priming is also related to apoptosis in vivo, given that in HIV-seropositive individuals, the frequency of specific CTLs depends on the proportion of peripheral CD40L+ apoptotic cells.

Transfection of the c-myc oncogene into normal Epstein-Barr virus-harboring B cells results in new phenotypic and functional features resembling those of Burkitt lymphoma cells and normal centroblasts.

Activated c-myc gene was introduced into the cells of three normal Epstein-Barr virus (EBV)-positive lymphoblastoid B cell lines (LCL). The cells were monitored for the appearance of new phenotypic and functional features compared with the control LCL cells transfected with plasmid that did not contain the c-myc gene. The LCL-expressing c-myc constitutively did not arrest growth in low serum concentration. However, the cell number in the cultures failed to increase because of substantial cell death. Death was due to apoptosis as demonstrated by flow cytometric analysis of propidium iodide-stained cells, by typical DNA laddering in gel electrophoresis, and by the inspection of Giemsa-stained cell smears. Apoptosis was also induced by exposing the transfected cells to antibodies directed to the immunoglobulin mu chain (a-mu-ab) irrespective of the serum concentration in the culture. Exposure of the cells to CD40 ligand (CD40L) or CD40 monoclonal antibody prevented cell apoptosis. Upon transfection with c-myc, the LCL cells acquired a vacuolated morphology that was never observed in control cells. Moreover, the expression of CD10 and CD38 was upregulated, while that of CD39 and especially CD23 was downregulated. Unlike that observed in certain Burkitt lymphoma (BL) cell lines that share the same surface phenotype (CD10+CD38+CD23-CD39-), the c-myc-transfected cells expressed lymphocyte function-associated (LFA) 1, LFA-3, and intercellular adhesion molecule 1 and grew in large clumps rather than single-cell layers. Expression of CD10 and CD38 was particularly evident on the cells undergoing apoptosis, thus suggesting a correlation between the presence of these markers and the apoptotic process. Cells placed in conditions favoring in vitro apoptosis displayed downregulation of Bcl-2 protein. Bcl-2 expression was, however, upregulated when the cells were exposed to CD40L. These data indicate that the B cells expressing c-myc constitutively acquire some of the features of normal centroblasts and of BL cells, including the expression of CD10 and CD38, and the propensity to undergo apoptosis, which can be prevented by exposure to CD40L. Therefore, these cells can serve as a model system to study both BL lymphomagenesis as well as the process of B cell selection occurring in the germinal centers.

Effects in live cells of a c-myc anti-gene PNA linked to a nuclear localization signal.

Peptide nucleic acids (PNA) are synthetic homologs of nucleic acids in which the phosphate-sugar polynucleotide backbone is replaced by a flexible polyamide. In this study, a PNA construct was employed as an anti-gene agent in intact cells in culture. The cell lines studied were derived from Burkitt's lymphomas (BL) that presented a translocated and hyperexpressed c-myc oncogene. A 17-mer anti-myc PNA, complementary to a unique sequence located at the beginning of the second exon of the oncogene, and was covalently linked at its N terminus to a nuclear localization signal (NLS) (PNA-myc(wt)-NLS). When BL cells were exposed to PNA-myc(wt)-NLS, the anti-gene construct was localized predominantly in the cell nuclei and a rapid consequent downregulation of c-myc expression occurred. Under these conditions, both completion of a productive cell cycle and apoptosis were inhibited.

(-)-Propranolol and (+/-)-cyanopindolol are mixed agonists-antagonists at serotonin autoreceptors in the hippocampus of the rat brain.

The effects of (-)-propranolol, (+)-propranolol and (+/-)-cyanopindolol on the release of [3H]5-hydroxytryptamine [( 3H]5-HT) were investigated in synaptosomes from the hippocampus of the rat, depolarized in superfusion with 15 mM KCl. (-)-Propranolol, but not (+)-propranolol, inhibited in a concentration-dependent way the K+-evoked release of [3H]5-HT. (+/-)-Cyanopindolol behaved similarly but was about 10 times more potent than (-)-propranolol. The inhibitory effects of (-)-propranolol and (+/-)-cyanopindolol were prevented by the autoreceptor antagonist methiothepin. Both beta-adrenoceptor antagonists antagonized the inhibition by exogenous 5-HT of the K+-evoked release of [3H]5-HT. The data suggest that some beta-adrenoceptor antagonists may behave as mixed agonists-antagonists at the 5-HT autoreceptor. Synaptosomes in superfusion appear to be particularly suitable to study separately agonistic compared to antagonistic activity of compounds having a mixed agonist-antagonist profile.

Constitutive expression of C-myc in nih 3t3 cells which coexpress the colony stimulating factor-I receptor and the catalytic domain of the gtpase-activating protein restores colony stimulating factor-I dependent mitogenic growth.

To begin to understand how ras p21 might be coupled to the human colony stimulating factor-1 receptor (CSF-IR), we compared the signaling properties of a CSF-IR containing a point mutation that converts the tyrosine at position 809 to a phenylalanine residue to signal transduction in cells that co-express the wild-type receptor and the catalytic domain of the GTPase activating protein (GAP(C)). We find that modulation of the immediate early gene c-myc and a delayed early response represented by the retrotransposon NVL3 were selectively impaired in both situations. Further, constitutive expression of c-myc in cells that contain GAP(C) restored CSF-1-dependent signal transduction. The data suggest a model in which information important for mitogenic cell.growth flows from the region of the receptor containing tyrosine 809, through ras p21, to c-myc in the nucleus.

Serotonin-glutamate interaction in rat cerebellum: involvement of 5-HT1 and 5-HT2 receptors.

The effects of serotonin (5-HT) on the release of endogenous glutamate (GLU) in rat cerebellum were investigated in slices depolarized with 35 mM K+. The Ca2+-dependent release of GLU was potently inhibited by 5-HT in a concentration-dependent way. Release was also inhibited by the 5-HT1 receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and by the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI). The inhibition by 10 nM 5-HT was partly (35-40%) counteracted by the 5-HT2 receptor antagonist ketanserin but was fully blocked by the mixed 5-HT1/5-HT2 receptor antagonist methiothepin. The effect of 8-OH-DPAT was not affected by ketanserin but was totally antagonized by methiothepin, while the effect of DOI was entirely suppressed by ketanserin. Ketanserin or methiothepin themselves increased (by 23 and 55%, respectively, at 10 nM) the K+-evoked release of GLU. In conclusion the release of endogenous GLU in rat cerebellum can be inhibited by 5-HT through receptors of the 5-HT1 and 5-HT2 type. The enhancement of GLU release by ketanserin or methiothepin could suggest a tonic inhibition. The possible localization of the 5-HT receptors involved in the interaction with the GLU systems is discussed.

Enhancement of endogenous GABA release from rat synaptosomal preparations is mediated by alpha 2-adrenoceptors pharmacologically different from alpha 2-autoreceptors.

The effects of various adrenergic agents on the release of endogenous gamma-aminobutyric acid (GABA) and of [3H]GABA were studied in superfused synaptosomal preparations from rat hippocampus. Noradrenaline (NA) enhanced in a concentration-dependent way the release of endogenous GABA but did not affect the release of the radioactive amino acid. The effect of NA was mimicked by the alpha 2-adrenoceptor agonist, clonidine, but not by the alpha 1-agonist, phenylephrine. Accordingly, NA was antagonized by the alpha 2-adrenoceptor antagonist, yohimbine, but not by the alpha 1-antagonist, prazosin. Both (+)-mianserin and (-)-mianserin, used as alpha 2-adrenoceptor blockers, counteracted the NA-evoked release of endogenous GABA. The results suggest that GABA released from hippocampus crude synaptosomes is modulated by alpha 2-adrenoceptors pharmacologically different from the alpha 2-autoreceptors that modulate NA release and previously found to be blocked by (+)-mianserin but not by the (-) enantiomer (Raiteri et al., 1983).

Dynamic ultrasonography of capsulo-ligamentous knee joint traumas.

Ultrasonography was performed on 10 patients with acute posttraumatic conditions of the knee in which X-ray films could exclude the presence of fractures. In 2 of 10 cases, the sonographic picture was normal; in the remaining 8 patients, ultrasonography disclosed capsulo-ligamentous lesions of different degrees of severity that were confirmed by surgery in 5 of 8 cases. The main sonographic signs of articular traumas were abnormal widening of the joint space (7 cases), intra-articular hemorrhage (8 cases), rupture of the medial collateral ligament (4 cases), or irregularity of its structure (3 cases). Ultrasonography is proposed as an effective and simple first-line method for the study of knee joint traumas. It can be performed in all cases presenting with painful joint swelling without radiographical evidence of fractures.

Ultrasonography in the diagnosis of soft tissue tumours.

The diagnosis of soft tissue tumours by the traditional instrumental methods often creates problems. Indeed, it is fairly difficult to make an accurate pre-operative diagnosis of a neoplasm of the soft tissues. The authors therefore employed ultrasonography to investigate 29 soft tissue tumours. They consider that ultrasonic assessment can make a valuable contribution to diagnosis in this type of pathology and provide information about the benign or malignant character of the neoplasm.