Dair approach in 7 infected total hip arthroplasties: our experience and current concepts of the literature

INTRODUCTION: Periprosthetic joint infection (PJI) is one of the most challenging complications following total hip arthroplasty. In early infection, within four to twelve weeks from surgery, debridement, antibiotics and implant retention (DAIR) can be the initial treatment. The aim of this study is to report our case series and review current concepts reported in the literature about this topic. MATERIALS AND METHODS: This was an observational cohort study that included 7 patients managed with DAIR for PJI following primary total hip replacement (THR) between 2014 and 2020. Inclusion criteria were a primary THR, direct anterior or lateral approach, DAIR procedure, and PJI. Exclusion criteria were a PJI following a revision total hip replacement or hemiarthroplasty, posterolateral approach, 1-stage revision, 2-stage revision, and Girdlestone procedure without prior DAIR. For each patient demographic characteristics, laboratory values, microorganisms involved, antibiotic therapy and outcome at one-year follow-up were registered. RESULTS: The mean duration between THR and DAIR was 19 days. In all cases only one DAIR procedure was performed. Most infections were caused by Staphylococcus aureus (4 cases) [one methicillin resistant (MRSA)]. The other infections were caused by Streptococcus agalactiae, Staphylococcus coagulase negative and Escherichia coli. At the final follow-up, the procedure was considered as successful in 6 out of 7 patients (85%). The one with unsuccessful outcome underwent to a two-stage revision. DISCUSSION: Our results were comparable with those of a recent systematic review of the literature. Factors that have been postulated to influence the outcome of DAIR in the management of PJIs include the timing and numbers of debridement, the exchange of components, the responsible microorganism and the duration of antibiotic treatment. In conclusion, the outcomes following DAIR are better as the indications are refined and risk factors identified. PJI prevention remains the key but the current literature still lacks well documented and effective PJI prevention protocols. (www.actabiomedica.it)

Antiplatelet drug ticagrelor enhances chemotherapeutic efficacy by targeting the novel P2Y12-AKT Pathway in pancreatic cancer cells

Background: Extensive research has reported that extracellular ADP in the tumour microenvironment can stimulate platelets through interaction with the platelet receptor P2Y12. In turn, activated platelets release biological factors supporting cancer progression. Experimental data suggest that the tumour microenvironment components, of which platelets are integral, can promote chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Thus, overcoming chemoresistance requires combining multiple inhibitors that simultaneously target intrinsic pathways in cancer cells and extrinsic factors related to the tumour microenvironment. We aimed to determine whether ticagrelor, an inhibitor of the ADP–P2Y12 axis and a well-known antiplatelet drug, could be a therapeutic option for PDAC. Methods: We investigated a functional P2Y12 receptor and its downstream signalling in a panel of PDAC cell lines and non-cancer pancreatic cells termed hTERT-HPNE. We tested the synergistic effect of ticagrelor, a P2Y12 inhibitor, in combination with chemotherapeutic drugs (gemcitabine, paclitaxel and cisplatin), in vitro and in vivo. Results: Knockdown studies revealed that P2Y12 contributed to epidermal growth factor receptor (EGFR) activation and the expression of SLUG and ZEB1, which are transcriptional factors implicated in metastasis and chemoresistance. Studies using genetic and pharmacological inhibitors showed that the P2Y12–EGFR crosstalk enhanced cancer cell proliferation. Inhibition of P2Y12 signalling significantly reduced EGF-dependent AKT activation and promoted the anticancer activity of anti-EGFR treatment. Importantly, ticagrelor significantly decreased the proliferative capacity of cancer but not normal pancreatic cells. In vitro, synergism was observed when ticagrelor was combined with several chemodrugs. In vivo, a combination of ticagrelor with gemcitabine significantly reduced tumour growth, whereas gemcitabine or ticagrelor alone had a minimal effect. Conclusions: These findings uncover a novel effect and mechanism of action of the antiplatelet drug ticagrelor in PDAC cells and suggest a multi-functional role for ADP-P2Y12 signalling in the tumour microenvironment

Is there a relation between clinical scores and serum ion levels after MoM-THA? One year results in 383 implants

Background and aim of the work: Adverse reaction to metal debris is the major cause of the high revision rates of metal on metal hip implants with femoral head size ≥ 36mm. Health authorities recommend regular surveillance even for asymptomatic individuals. The main investigations used are Co+ and Cr+ serum levels, x-rays and, eventually, ultrasound and MARS-MRI. Clinic is also assessed. The aim of this study is to identify if there is a relation between ion levels and the clinical scores in order to evaluate the outcome and plan the correct management after this type of implant. Methods: 383 subjects were included and divided in 3 groups (serum ion levels >, < and >60 µg/L). Co+, Cr+, HHS and OHS results of 1 year (2017) were analysed in order to show a correlation between ion levels and clinical scores. Results: Clinical scores were similar in group 1 and 2. Differences were observed comparing the group 1 and 2 with group 3 for both variables. Discussion and Conclusions: Surveillance algorithms have been introduced by health authorities. Nevertheless, the indication to revision surgery is not simple especially in those cases in which a discrepancy between clinic and investigations is present. In this study clinical scores seem to be less important than ion levels in the evaluation of outcomes and in order to plan the correct management in the majority of cases. Larger studies are needed to highlight the real importance of clinical scores in the decision making after these type of implants

Transient magnetic domain wall ac dynamics by means of magneto-optical Kerr effect microscopy

The domain wall response under constant external magnetic fields reveals a complex behavior where sample disorder plays a key role. Furthermore, the response to alternating magnetic fields has only been explored in limited cases and analyzed in terms of the constant field solution. Here we unveil phenomena in the evolution of magnetic domain walls under the application of alternating magnetic fields within the creep regime, well beyond a small fuctuation limit of the domain wall position. Magnetic field pulses were applied in ultra-thin ferromagnetic films with perpendicular anisotropy, and the resulting domain wall evolution was characterized by polar magneto-optical Kerr effect microscopy. Whereas the DC characterization is well predicted by the elastic interface model, striking unexpected features are observed under the application of alternating square pulses: magneto-optical images show that after a transient number of cycles, domain walls evolve toward strongly distorted shapes concomitantly with a modification of domain area. The morphology of domain walls is characterized with a roughness exponent when possible and contrasted with alternative observables which result to be more suitable for the characterization of this transient evolution. The final stationary convergence as well as the underlying physics is discussed.Comment: 9 pages, 8 figure

Results of the Patient-Related Outcomes of Mechanical lead Extraction Techniques (PROMET) study: a multicentre retrospective study on advanced mechanical lead extraction techniques.

AIMS: Several large studies have documented the outcome of transvenous lead extraction (TLE), focusing on laser and mechanical methods. To date there has been no large series addressing the results obtained with rotational lead extraction tools. This retrospective multicentre study was designed to investigate the outcomes of mechanical and rotational techniques. METHODS AND RESULTS: Data were collected on a total of 2205 patients (age 66.0 ± 15.7 years) with 3849 leads targeted for extraction in six European lead extraction centres. The commonest indication was infection (46%). The targeted leads included 2879 pacemaker leads (74.8%), 949 implantable cardioverter-defibrillator leads (24.6%), and 21 leads for which details were unknown; 46.6% of leads were passive fixation leads. The median lead dwell time was 74 months [interquartile range (IQR) 41-112]. Clinical success was obtained in 97.0% of procedures, and complete extraction was achieved for 96.5% of leads. Major complications occurred in 22/2205 procedures (1%), with a peri-operative or procedure-related mortality rate of 4/2205 (0.18%). Minor complications occurred in 3.1% of procedures. A total of 1552 leads (in 992 patients) with a median dwell time of 106 months (IQR 66-145) were extracted using the Evolution rotational TLE tool. In this subgroup, complete success was obtained for 95.2% of leads with a procedural mortality rate of 0.4%. CONCLUSION: Patient outcomes in the PROMET study compare favourably with other large TLE trials, underlining the capability of rotational TLE tools and techniques to match laser methods in efficacy and surpass them in safety

Cation distribution in manganese cobaltite spinels Co3−xMnxO4 (0 ≤ x ≤ 1) determined by thermal analysis

Thermogravimetric analysis was used in order to study the reduction in air of submicronic powders of Co3−x Mn x O4 spinels, with 0 ≤ x ≤ 1. For x = 0 (i.e. Co3O4), cation reduction occurred in a single step. It involved the CoIII ions at the octahedral sites, which were reduced to Co2+ on producing CoO. For 0 < x ≤ 1, the reduction occurred in two stages at increasing temperature with increasing amounts of manganese. The first step corresponded to the reduction of octahedral CoIII ions and the second was attributed to the reduction of octahedral Mn4+ ions to Mn3+. From the individual weight losses and the electrical neutrality of the lattice, the CoIII and Mn4+ ion concentrations were calculated. The distribution of cobalt and manganese ions present on each crystallographic site of the spinel was determined. In contrast to most previous studies that took into account either CoIII and Mn3+ or Co2+, CoIII and Mn4+ only, our thermal analysis study showed that Co2+/CoIII and Mn3+/Mn4+ pairs occupy the octahedral sites. These results were used to explain the resistivity measurements carried out on dense ceramics prepared from our powders sintered at low temperature (700–750 °C) in a Spark Plasma Sintering apparatus

Fluid Structure Interaction of Multiple Flapping Filaments Using Lattice Boltzmann and Immersed Boundary Methods

The problem of flapping filaments in an uniform incoming flow is tackled using a Lattice Boltzmann—Immersed Boundary method. The fluid momentum equations are solved on a Cartesian uniform lattice while the beating filaments are tracked through a series of markers, whose dynamics are functions of the forces exerted by the fluid, the filament flexural rigidity and the tension. The instantaneous wall conditions on the filament are imposed via a system of singular body forces, consistently discretised on the lattice of the Boltzmann equation. We first consider the case of a single beating filament, and then the case of multiple beating filaments in a side-by-side configuration, focussing on the modal behaviour of the whole dynamical systems

Digital droplet PCR is a specific and sensitive tool for detecting IDH2 mutations in acute myeloid leukemia patients

Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) interfere with cellular metabolism contributing to oncogenesis. Mutations of IDH2 at R140 and R172 residues are observed in 20% of acute myeloid leukemias (AML), and the availability of the IDH2 inhibitor Enasidenib made IDH2 mutational screening a clinical need. The aim of this study was to set a new quantitative polymerase chain reaction (PCR) technique, the drop-off digital droplet PCR (drop-off ddPCR), as a sensitive and accurate tool for detecting IDH2 mutations. With this technique we tested 60 AML patients. Sanger sequencing identified 8/60 (13.5%) mutated cases, while ddPCR and the amplification refractory mutation system (ARMS) PCR, used as a reference technique, identified mutations in 13/60 (21.6%) cases. When the outcome of IDH2-mutated was compared to that of wild-type patients, no significant difference in terms of quality of response, overall survival, or progression-free survival was observed. Finally, we monitored IDH2 mutations during follow-up in nine cases, finding that IDH2 can be considered a valid marker of minimal residual disease (MRD) in 2/3 of our patients. In conclusion, a rapid screening of IDH2 mutations is now a clinical need well satisfied by ddPCR, but the role of IDH2 as a marker for MRD still remains a matter of debate

Recurrences of ventricular tachycardia after stereotactic arrhythmia radioablation arise outside the treated volume: analysis of the swiss cohort

BACKGROUND AND AIMS Stereotactic arrhythmia radioablation (STAR) has been recently introduced for the management of therapy-refractory ventricular tachycardia (VT). VT recurrences have been reported after STAR but the mechanisms remain largely unknown. We analyzed recurrences in our patients after STAR. METHODS From 09.2017 to 01.2020, 20 patients (68±8y, LVEF 37±15%) suffering from refractory VT were enrolled, 16/20 with a history of at least 1 electrical storm. Before STAR, an invasive electro-anatomical mapping (Carto3) of the VT substrate was performed. A mean dose of 23±2Gy was delivered to the planning target volume (PTV). RESULTS The median ablation volume was 26 ml (range 14-115) and involved the interventricular septum in 75% of patients. During the first 6 months after STAR, VT burden decreased by 92% (median value, from 108 to 10 VT/semester). After a median follow-up of 25 months, 12/20 (60%) developed a recurrence and underwent a redo ablation. VT recurrence was located in proximity of the treated substrate in 9 cases, remote from the PTV in 3 cases and involved a larger substrate over ≥3 LV segments in 2 cases. No recurrences occurred inside the PTV. Voltage measurements showed a significant decrease in both bipolar and unipolar signal amplitude after STAR. CONCLUSION STAR is a new tool available for the treatment of VT, allowing for a significant reduction of VT burden. VT recurrences are common during follow-up, but no recurrences were observed inside the PTV. Local efficacy was supported by a significant decrease in both bipolar and unipolar signal amplitude