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Alzheimer’s disease is the most common form of dementia. Notwithstanding the huge investments in drug development, only one disease-modifying treatment has been recently approved. Here we present a single-cell-led systems biology pipeline for the identification of drug repurposing candidates. Using single-cell RNA sequencing data of brain tissues from patients with Alzheimer’s disease, genome-wide association study results, and multiple gene annotation resources, we built a multi-cellular Alzheimer’s disease molecular network that we leveraged for gaining cell-specific insights into Alzheimer’s disease pathophysiology and for the identification of drug repurposing candidates. Our computational approach pointed out 54 candidate drugs, mainly targeting MAPK and IGF1R signaling pathways, which could be further evaluated for their potential as Alzheimer’s disease therapy.

Introduction: Articular surface replacement (ASR) XL implants exhibit higher-than-expected revision rates, blood ion concentrations and soft tissue lesions, making revisions troublesome and potentially unsatisfying. Appropriate techniques and outcomes in ASR XL revisions are rarely documented. The aims of this study were the assessments of pre-revision data, post-revision clinical and radiographic outcomes and ion levels in isolated acetabular ASR XL revisions performed using highly porous titanium cups and Delta ceramic articulations. Methods: 18 isolated acetabular ASR XL revisions in 16 patients were performed using Ti-Por cups (Adler Ortho, Milan, Italy) and Delta bearings (CeramTec, Plochingen, Germany). Pre-revision demographic, clinical, radiological and implant-related features were assessed. Clinical and radiographic parameters (cup positioning, osseointegration) after revisions were evaluated at a minimum follow-up of 5 years. Ion concentrations in blood and urine were collected in pre-revision setting and 1 year after revision. Results: 4 complications occurred in 3 different revisions (16.7%), 1 dislocation, 2 infections, 1 psoas impingement. No re-revision was performed at 5 years (1 scheduled arthroscopy). Good clinical outcomes were achieved (HHS score: 88.3 ± 9.2). All the cups showed reassuring signs of osseointegration (>3 parameters). Blood ion concentrations significantly decreased: patients with Co blood ion concentration over the threshold (7 μg/l) decreased from 76.5% to 0%. No pre-revision or intraoperative data influenced the revision outcomes. Conclusions: Highly porous titanium cups and Delta ceramic articulations provided reliable mid-term clinical and radiographic outcomes in isolated acetabular ASR XL revisions. Ion concentrations significantly decreased. Multicentre prospective controlled studies are required to confirm these preliminary outcomes.

Introduction: Aim of this study was to describe the clinical outcomes of 16 patients with iliopsoas (IP) impingement after primary total hip arthroplasty (THA), treated with an arthroscopic tendon release. Methods: 16 patients (11 females/5 males), with a mean age of 57.8 ± 11.1 years (age at THA: 54.4 ± 11 years) and a diagnosis of IP impingement after primary THA, were treated with the Wettstein tenotomy. Preoperatively, every patient underwent a diagnostic ultrasonography guided peritendinous injection and a computed tomography (CT) scan. Every patient was clinically evaluated using WOMAC score. Subjective pain relief and active hip flexion strength were measured. Results: No complications related to arthroscopy were detected. Every cup was prominent with a mean axial overhang of 13 ± 4.8 mm (range 5–20 mm). At a mean follow-up of 27 ± 20.1 months (range 6–48 months), the WOMAC score was 83.7 ± 10.1 points. 13 patients out of 16 (81.3%) had a complete pain relief. 14 patients out of 16 (88%) regained full active hip flexion strength at the final follow-up. 1 patient was scheduled for cup revision after 6 months, due to persistent symptomatology. No demographic data or CT measurements about cup position statistically influenced the outcome. Conclusions: When preceded by an appropriate diagnosis, arthroscopic tenotomy proved safe and effective for IP impingement, regardless the magnitude of cup protrusion.

Objectives: The aim of this study was to evaluate the middle term cup survival, assess the functional implementation and the radiographic evolution of tantalum acetabular cups implanted on patients with a history of pelvic radiotherapy. Methods: From 2005 to 2013, we performed 12 THA replacements (4 males 8 females; mean age: 46.6 years (range 25–75)) on irradiated bone with Trabecular metal acetabular cups, 8 primary implants and 4 revision implants. The mean radiation dose delivered was 5500 cGy (range 3000 cGy–13,600 cGy). The mean follow-up was 68 months, ranging from 38 to 136. Postoperative follow-up time was assessed at 1, 3, 6 and 12 months, then annually. Double projection radiographs were requested at each control. Radiographic signs of loosening were investigated by X-rays looking for radiolucent lines. We used the Harris hip score for the clinical and functional evaluation. Results: To now none of the 12 patients in the series needed any revision surgery for aseptic loosening. In the revision group one patient have been revised for septic loosening, two patients have been treated by conservative procedure for hip dislocation. Post-operative Harris hip score improved from an average of 46 points to 85.3 points. At last follow-up we found only in one case radiographic signs of progressive lucent line, without clinical sign of failure. Conclusion: In a clinical setting, tantalum cup seems to provide a good stability due to the integration of the trabecular metal to the underline cancellous bone. The reported results, in agreement with literature data, propose the use of tantalum cups in irradiated bone. Level of evidence: Level IV, therapeutic study. Keywords: Hip, Arthroplasty, Uncemented cup, Tantalum, Radiotherapy, Tumor

The accuracy of scintigraphic evidence of perfusion defects, even when classified as 'high probability' by matching with ventilation techniques or thoracic roentenograms is unsatisfactory when used without a pre-test clinical evaluation of probability. Although unusual, a complete or near-complete unilateral absence of perfusion in a lung with normal perfusion controlaterally must alert clinicians to the possibility of a false-positive result. In such instances, the administration of therapeutic dosages of fibrinolitic and antithrombotic agents (or even surgery) may lead to deleterious consequences. We report a patient with malignancy causing extrinsic narrowing of the pulmonary artery leading to a drastic impairment in the perfusion of an entire lung, compatible with, but not diagnostic of massive pulmonary embolism.