2-Substituted 1,5-benzothiazepine-based HDAC inhibitors exert anticancer activities on human solid and acute myeloid leukemia cell lines.

Herein, we report the development of a new series of histone deacetylase inhibitors (HDACi) containing a 2-substituted 1,5-benzothiazepine scaffold. First, a virtual combinatorial library (∼1.6 × 103 items) was built according to a convenient synthetic route, and then it was submitted to molecular docking experiments on seven HDACs isoforms belonging to classes I and II. Integrated computational filters were used to select the most promising ones that were synthesized through an optimized approach, also amenable to generating both racemic and enantioenriched benzothiazepine-based derivatives. The obtained compounds showed potent HDAC inhibitory activity, especially those containing the sulphone moiety, endowed with IC50 in the nanomolar range. In addition, in vitro outcomes of our synthesized compounds demonstrated a cytotoxic effect on U937 and HCT116 cell lines and an arrest in the G2/M phase (13 ≤ IC50 ≤ 18 µM). Finally, Western blot analyses outlined the modulation of the histone acetyl markers such as H3K9/14, acetyl-tubulin, and the apoptotic indicator p21 in both cancer cell lines, disclosing a good HDAC inhibitor activity exerted by the designed items. Given the key role of HDACs in many cellular pathways, which makes these enzymes appealing and "hot" drug targets, our findings highlighted the importance of these 2-substituted 1,5-benzothiazepine-based compounds (both in the reduced and oxidized version) for the development of novel epidrugs.

Unicompartimental knee arthroplasty metallosis treated with uni-on-uni revision: A case report.

BACKGROUND: Metallosis is the result of metallic wear debris in the soft tissues and is associated to both local and systemic inflammatory response. Metallosis has been reported after total hip and total knee arthroplasty (TKA), but rarely after a unicompartimental knee arthroplasty (UKA). In the context of UKA metallosis, surgeons often opt for revision using a TKA. However, in this paper, the authors successfully treated UKA revising the metal back only. CASE SUMMARY: Prior to treat our patient we conducted a literature research through which we identified eleven cases of metallosis after UKA, ten (90.9%) were treated revising using though a TKA. Only one case was managed through a uni-on-uni revision, reporting high knee function. Our patient complained worsening pain and function after a snap occurred at 16 mo after UKA implantation. At 18 mo following surgical debridment and uni-on-uni revision surgery, our patient exhibited a relevant improvement in Oxford Knee Score and a reduction of metal ion levels in the blood. CONCLUSION: Our study highlights that in case of metallosis after UKA, the treatment may be based on surgical debridement and just revising the mobilized components.

SuperPath approach is a recommendable option in frail patients with femoral neck fractures: a case-control study.

INTRODUCTION: The treatment of intracapsular femoral neck fractures (FNFs) in the elderly is usually based on hip replacement, both total hip arthroplasty (THA) and hemiarthroplasty (HA). Recently, several tissue-sparing approaches for hip arthroplasty had been described with promising results in terms of hospitalization length, blood loss and dislocation rate. The aim of the present study was to compare the blood loss and the transfusion rate in a cohort of patients with FNF treated using an HA through both the SuperPath (SP) and the traditional posterolateral (PL) approaches. MATERIALS AND METHODS: We retrospectively collected data from patients affected by FNFs between January 2018 and February 2020. All patients with intracapsular FNF treated with a single HA implant (Profemur L, MicroPort Orthopedics Inc., USA) via PL or SP approaches were included. Exclusion criteria were pathological fractures, polytrauma and preoperatively transfused patients. RESULTS: Thirty-five patients were included and analysed in the present study. 17 patients were classified in the SP group, and 18 in the PL one. The rate of antithrombotic therapy was higher in the SP group compared with the PL group [10 (58, 82%) vs 4 (22, 2%)]. While the two groups did not differ in terms of preoperative haemoglobin (Hb), 48 h postoperative Hb and Hb reduction, a significative difference was observed in terms of blood transfusion rate (1 SP vs 9 PL, p = 0.0072). CONCLUSIONS: The SuperPath approach in patients with FNF under antithrombotic therapy assures lower transfusion rate, potentially reducing complication rates and improving patients' outcomes.

Atypical periprosthetic femoral fractures of the hip: A PRISMA compliant systematic review.

INTRODUCTION: Long-term use of bisphosphonates (BPs) is associated with Atypical Femoral Fracture (AFF). Theoretically, periprosthetic femoral fractures (PFF) should be excluded from the diagnosis of AFF. However, recently several studies reported the occurrence of PPFs around a hip arthroplasty presenting features of an AFF. The present study describes the characteristics of Atypical Periprosthetic Femoral Fracture (APFF) and evaluates the effectiveness of their management through a PRISMA compliant systematic review of the published case reports and series. MATERIALS AND METHODS: A literature search was performed using "periprosthetic fracture" and "atypical femoral fracture" as keywords. Patients demographics, drug use, clinical and imaging characteristics, stem fixation and classification, management strategies for APFF and patients' outcomes, were also collected. RESULTS: The present review included and analysed 17 patients from 12 studies. All APFFs occurred in females with a mean age of 75.9 years of age (range 43-87). In 11 patients, APFFs occurred around an uncemented stem, and in 6 around a cemented stem. Ten fractures were incomplete, and 7 complete. Conservative management was effective in 4 of 10 patients with incomplete fracture, while all patients with complete fractures underwent open reduction and internal fixation. A fracture non-union was observed in 5 patients and further surgery was required. DISCUSSIONS: APFFs share several clinical and imaging characteristics with AFF. An appropriate and early diagnosis may allow to improve the outcome of these fractures, the management of which should be based on the same principles of that of AFFs. CONCLUSIONS: Considering the low quality of published articles and the heterogeneity of the treatment used, a clear recommendation of the most appropriate treatment cannot be formulated.

Preliminary results of autologous adipose-derived stem cells in early knee osteoarthritis: identification of a subpopulation with greater response.

PURPOSE: The purpose of this study was to report the clinical and functional results of a series of patients with early knee osteoarthritis (KOA) treated with the intra-articular injection of autologous adipose-derived stem cells (aASCs) plus arthroscopic debridement. The hypothesis was that protocol would significantly improve the clinical and functional outcomes in patients with early KOA. METHODS: Fifty-two patients with early KOA, who received arthroscopic debridement followed by percutaneous injection of aASCs, were enrolled into the study and retrospectively analyzed with an average follow-up of 15.3 (range, 6 to 24) months. Patients were assessed through the IKS knee and function scores and VAS pain scale. RESULTS: The mean IKS knee score improved from 37.4 (range, 14 to 79) points pre-operatively to 62.6 (range, 27 to 95) points at the latest follow-up (p < < 0.01). The mean IKS function score improved from 57.2 (range, 25 to 100) points pre-operatively to 83.0 (range, 35 to 100) points at the latest follow-up (p < < 0.01). The mean VAS score decreased from 8.5 (range, 3 to 10) pre-operatively to 5.1 (range, 0 to 8) at the latest follow-up (p < < 0.01). Additionally, patients with a pre-operative VAS score greater than 8 were found to show greater clinical and functional benefits compared with patients with VAS score lower than 8. CONCLUSIONS: The knee injection of aASCs associated to arthroscopic debridement increased significantly the clinical and functional scores in patients with early KOA at a mid-term follow-up, especially those with higher pre-operative VAS scores.