Tumor metastasis to bone

Establishment of skeletal metastasis involves bidirectional interactions between the tumor cell and the cellular elements in the bone microenvironment. A better understanding of the pathophysiology of bone metastasis will be critical in developing the means to prevent bone metastasis or inhibit its progression. The receptor activator of nuclear factor-κB (RANK)/RANK ligand pathway has emerged as the key pathway regulating osteolysis in skeletal metastasis. A number of candidate factors, including the Wnt (wingless int) proteins, endothelin-1, and bone morphogenetic proteins, have been implicated in the establishment of osteoblastic metastasis. The complex nature of tumor-bone microenvironment interactions and the presence of multiple pathways that lead to bone metastasis suggests that simultaneous targeting of these pathways in the metastatic cascade are required for effective treatment. This review discusses current understanding of the pathophysiologic mechanisms that underlie the establishment of bone metastasis and potential molecular therapeutic strategies for prevention and treatment of bone metastasis

In vitro evaluation of a double-stranded self-complementary adeno-associated virus type2 vector in bone marrow stromal cells for bone healing

Background: Both adenoviral and lentiviral vectors have been successfully used to induce bone repair by over-expression of human bone morphogenetic protein 2 (BMP-2) in primary rat bone marrow stromal cells in pre-clinical models of ex vivo regional gene therapy. Despite being a very efficient means of gene delivery, there are potential safety concerns that may limit the adaptation of these viral vectors for clinical use in humans. Recombinant adeno-associated viral (rAAV) vector is a promising viral vector without known pathogenicity in humans and has the potential to be an effective gene delivery vehicle to enhance bone repair. In this study, we investigated gene transfer in rat and human bone marrow stromal cells in order to evaluate the effectiveness of the self-complementary AAV vector (scAAV) system, which has higher efficiency than the single-stranded AAV vector (ssAAV) due to its unique viral genome that bypasses the rate-limiting conversion step necessary in ssAAV.Methods: Self-complementaryAAV2 encoding GFP and BMP-2 (scAAV2-GFP and scAAV2-BMP-2) were used to transduce human and rat bone marrow stromal cells in vitro, and subsequently the levels of GFP and BMP-2 expression were assessed 48 hours after treatment. In parallel experiments, adenoviral and lentiviral vector mediated over-expression of GFP and BMP-2 were used for comparison.Results: Our results demonstrate that the scAAV2 is not capable of inducing significant transgene expression in human and rat bone marrow stromal cells, which may be associated with its unique tropism.Conclusions: In developing ex vivo gene therapy regimens, the ability of a vector to induce the appropriate level of transgene expression needs to be evaluated for each cell type and vector used. © 2011 Alaee et al; licensee BioMed Central Ltd

Two-year minimum survivorship and radiographic analysis of a pressfit short humeral stem for total shoulder arthroplasty

Newer generation humeral stem designs in total shoulder arthroplasty (TSA) are trending towards shorter lengths and uncemented fixation. The goal of this study is to report a 2-yr minimum clinical and radiographic outcomes of an uncemented short-stem press-fit humeral stem in anatomic total shoulder arthroplasty (ATSA) and reverse total shoulder arthroplasty (RTSA). A retrospective multicenter database review was performed of all patients who received an uncemented short-length press-fit humeral stem (Equinoxe Preserve humeral stem, Exactech, Inc., Gainesville, FL, USA) in ATSA and RTSA with a minimum two-year follow-up. The primary outcome was the prevalence of humeral stems at risk of radiographic loosening. Secondary outcomes included evaluation of functional outcome scores and prevalence of revision TSA for humeral stem loosening. Two blinded observers performed radiographic analyses, which included humeral stem alignment, canal filling ratio, radiolucent lines, stress shielding (calcar and greater tuberosity), and changes in component position (subsidence and stem shift). At risk stems were defined by the presence of one or more of the following: humeral stem with shifting or subsidence, scalloping of the humeral cortex, or radiolucent lines measuring 2 mm or greater in 3 or more zones. 287 patients (97 ATSA and 190 RTSA) were included in this study. The mean follow-up was 35.9 (±6.1) months. There were significant improvements for all functional outcome scores (P < .05), range of motion (P < .05), and visual analogue pain scale pain (P < .05). The prevalence of humeral stem at risk of radiographic loosening was 1% in the ATSA group (1/97) and 18.4% in the RTSA group (35/190). Calcar resorption was seen in 34% of ATSA and 19% of RTSA, with severe resorption in 12.4% of ATSA and only 3.2% of RTSA. Greater tuberosity resorption was present in 3.1% of ATSA and 7.9% of RTSA. The mean canal filling ratio was 50.2% (standard deviation 11.2%). Using logistic regression, a significant positive correlation between canal filling ratio and stress shielding (P < .01) was seen for both calcar and tuberosity stress shielding. The revision surgery rate was 0% in ATSA compared to 1.6% in RTSA. This retrospective study demonstrates a low revision rate and low prevalence of humeral stems at risk of radiographic loosening at two years with a press-fit short-stem humeral design in ATSA. Physiologic subsidence of humeral stems can account for higher prevalence of humeral stems at radiographic risk of loosening in RTSA compared to ATS

The Evolution of Reverse Total Shoulder Arthroplasty and Its Current Use in the Treatment of Proximal Humerus Fractures in the Older Population

Proximal humerus fracture (PHF) is a common injury in the older population. While the majority of these fractures are treated non-operatively, a small subset of patients may benefit from surgical treatment. However, there continues to be an ongoing debate regarding the indications and ideal surgical treatment strategy. The use of reverse total shoulder arthroplasty (RTSA) has resulted in a paradigm shift in the treatment of PHFs in the older population. Unique biomechanical principles and design features of RTSA make it a suitable treatment option for PHFs in the older population. RTSA has distinct advantages over hemiarthroplasty and internal fixation and provides good pain relief and a reliable and reproducible improvement in functional outcomes. As a result, there has been an exponential increase in the volume of RTSA in the older population in last decade. The aim of this paper is to review the current concepts, outcomes and controversies regarding the use of RTSA for the treatment of PHFs in the older population

Multicentric giant cell tumor involving the same foot: A case report and review of literature

Multicentric giant cell tumour (GCT) is extremely rare; no case has been previously reported where two lesions occurred in the same foot at different sites. We report a case involving the calcaneus and subsequently the 3rd toe of the same foot and review the reported literature. In established cases of multicentricity, the histopathology has to be properly reviewed and the patient has to be followed up for a longer time with serial whole body assessment to pick up any subsquent lesions. The treatment of the local disease does not differ from a standard GCT

Mask-Related Glasses Fogging: A Predisposing Mechanism of Falls during the COVID-19 Pandemic

Fogging is a relatively infrequent, yet annoying, issue encountered by individuals who wear glasses. With the arrival of COVID-19, glasses fogging is more common due to the ubiquitous use of face masks. Individuals are stuck wrestling between leaving their mask off or trying to navigate their day-to-day lives with fogged glasses and risk falling. We report a case of an olecranon fracture sustained due to reduced visibility secondary to mask-related fogging during the COVID-19 pandemic. The recommendations included here will provide health care providers with the necessary information to educate patients regarding prevention of mask-related glass fogging

Clinical outcomes of open Latarjet-Patte procedures performed for recurrent anterior shoulder instability with primary bone loss versus failed arthroscopic Bankart repair

Background This study compares the outcomes of Latarjet-Patte procedures (LPs) performed for primary glenohumeral instability in the setting of critical bone loss (LP-BL) versus salvage surgery performed after a failed arthroscopic Bankart repair (LP-FB). Methods LP's performed by senior author from 2017 to 2021 were separated into cohorts by LP indication. Data abstracted from electronic medical records included demographic information, preoperative clinical scores, radiological imaging, and complications. Postoperative clinical outcome scores collected after a 2-year minimum follow-up included: patient-reported outcomes measurement information system (PROMIS) upper extremity (UE), PROMIS pain interference, PROMIS pain intensity, American Shoulder and Elbow Surgeons (ASES), and visual analog scale pain scores. Results A total of 47 patients (LP-BL: n=29, LP-FB: n=18) with a mean age of 29 years (range, 15–58 years) were included in this study. Both cohorts achieved good upper extremity functionality without significant differences as indicated by mean PROMIS UE (LP-BL: 52.6±10.0 vs. LP-FB: 54.6±7.6, P=0.442) and ASES score (LP-BL: 89.9±15.7 vs. LP-FB: 91.5±14.4, P=0.712). However, the LP-FB cohort reported lower levels of pain (LP-FB: 0.5±1.1 vs. LP-BL: 1.9±2.7, P=0.020) at their latest follow-up. There were no significant differences in complication rates including re-dislocation between cohorts (LP-BL: 2/29 [6.9%] vs. LP-FB: 2/18 [11.1%], P=0.629). Conclusions When performed after failed Bankart repair, the LP results in similar postoperative functional outcomes and similar rates of complications and re-dislocations when compared to the primary indication of recurrent glenohumeral instability in the setting of critical bone loss. Level of evidence III