Search

Abstract Case We present the case of a 73-year-old female with an acromioclavicular joint cyst associated with atypical, exquisite, progressive pain, and imaging findings concerning for neoplastic etiology. She underwent en bloc resection of the trapezium containing this cystic mass and distal clavicle. Surgical pathology demonstrated findings consistent with a large ganglion cyst without evidence of malignancy. Conclusion Our case serves to emphasize the importance of stepwise evaluation and appropriate treatment of such cysts while utilizing appropriate principles of oncologic resection in cases where a neoplastic etiology is considered.

Introduction: The landscape of drug-drug interactions (DDIs) has evolved significantly over the past 60 years, necessitating a retrospective analysis to identify research trends and under-explored areas. While methodologies like bibliometric analysis provide valuable quantitative perspectives on DDI research, they have not successfully delineated the complex interrelations between drugs. Understanding these intricate relationships is essential for deciphering the evolving architecture and progressive transformation of DDI research structures over time. We utilize network analysis to unearth the multifaceted relationships between drugs, offering a richer, more nuanced comprehension of shifts in research focus within the DDI landscape.Methods: This groundbreaking investigation employs natural language processing, techniques, specifically Named Entity Recognition (NER) via ScispaCy, and the information extraction model, SciFive, to extract pharmacokinetic (PK) and pharmacodynamic (PD) DDI evidence from PubMed articles spanning January 1962 to July 2023. It reveals key trends and patterns through an innovative network analysis approach. Static network analysis is deployed to discern structural patterns in DDI research, while evolving network analysis is employed to monitor changes in the DDI research trend structures over time.Results: Our compelling results shed light on the scale-free characteristics of pharmacokinetic, pharmacodynamic, and their combined networks, exhibiting power law exponent values of 2.5, 2.82, and 2.46, respectively. In these networks, a select few drugs serve as central hubs, engaging in extensive interactions with a multitude of other drugs. Interestingly, the networks conform to a densification power law, illustrating that the number of DDIs grows exponentially as new drugs are added to the DDI network. Notably, we discovered that drugs connected in PK and PD networks predominantly belong to the same categories defined by the Anatomical Therapeutic Chemical (ATC) classification system, with fewer interactions observed between drugs from different categories.Discussion: The finding suggests that PK and PD DDIs between drugs from different ATC categories have not been studied as extensively as those between drugs within the same categories. By unearthing these hidden patterns, our study paves the way for a deeper understanding of the DDI landscape, providing valuable information for future DDI research, clinical practice, and drug development focus areas.

Background:. Although guidelines recommend primary care–driven management of NAFLD, workflow constraints hinder feasibility. Leveraging electronic health records to risk stratify patients proposes a scalable, workflow-integrated strategy. Materials and Methods:. We prospectively evaluated an electronic health record-embedded clinical decision support system’s ability to risk stratify patients with NAFLD and detect gaps in care. Patients missing annual laboratory testing to calculate Fibrosis-4 Score (FIB-4) or those missing necessary linkage to further care were considered to have a gap in care. Linkage to care was defined as either referral for elastography-based testing or for consultation in hepatology clinic depending on clinical and biochemical characteristics. Results:. Patients with NAFLD often lacked annual screening labs within primary care settings (1129/2154; 52%). Linkage to care was low in all categories, with

Prioritizing drug repurposing candidates for downstream studies remains challenging. Here, the authors present a high-throughput approach to identify and validate drug repurposing candidates, integrating human gene expression, drug perturbation, and clinical data from publicly available resources.

T‐lymphokine‐activated killer (T‐LAK) cell‐originated protein kinase (TOPK) is an emerging target with critical roles in various cancers; however, its expression and function in osteosarcoma remain unexplored. We evaluated TOPK expression using RNA sequencing and gene expression data from public databases (TARGET‐OS, CCLE, GTEx, and GENT2) and immunohistochemistry in an osteosarcoma tissue microarray (TMA). TOPK gene expression was significantly higher in osteosarcoma than normal tissues and directly correlated with shorter overall survival. TOPK was overexpressed in 83.3% of the osteosarcoma specimens within our TMA and all osteosarcoma cell lines, whereas normal osteoblast cells had no aberrant expression. High expression of TOPK associated with metastasis, disease status, and shorter overall survival. Silencing of TOPK with small interfering RNA (siRNA) decreased cell viability, and inhibition with the selective inhibitor OTS514 suppressed osteosarcoma cell proliferation, migration, colony‐forming ability, and spheroid growth. Enhanced chemotherapeutic sensitivity and a synergistic effect were also observed with the combination of OTS514 and either doxorubicin or cisplatin in osteosarcoma cell lines. Taken together, our study demonstrated that TOPK is a potential prognostic biomarker and therapeutic target for osteosarcoma treatment.

Background: COVID-19 patients with underlying medical conditions are vulnerable to drug-drug interactions (DDI) due to the use of multiple medications. We conducted a discovery-driven data analysis to identify potential DDIs and associated adverse events (AEs) in COVID-19 patients from the FDA Adverse Event Reporting System (FAERS), a source of post-market drug safety.Materials and Methods: We investigated 18,589 COVID-19 AEs reported in the FAERS database between 2020 and 2021. We applied multivariate logistic regression to account for potential confounding factors, including age, gender, and the number of unique drug exposures. The significance of the DDIs was determined using both additive and multiplicative measures of interaction. We compared our findings with the Liverpool database and conducted a Monte Carlo simulation to validate the identified DDIs.Results: Out of 11,337 COVID-19 drug-Co-medication-AE combinations investigated, our methods identified 424 signals statistically significant, covering 176 drug-drug pairs, composed of 13 COVID-19 drugs and 60 co-medications. Out of the 176 drug-drug pairs, 20 were found to exist in the Liverpool database. The empirical p-value obtained based on 1,000 Monte Carlo simulations was less than 0.001. Remdesivir was discovered to interact with the largest number of concomitant drugs (41). Hydroxychloroquine was detected to be associated with most AEs (39). Furthermore, we identified 323 gender- and 254 age-specific DDI signals.Conclusion: The results, particularly those not found in the Liverpool database, suggest a subsequent need for further pharmacoepidemiology and/or pharmacology studies.

Abstract Extremity reconstruction surgery is increasingly performed rather than amputation for patients with large-segment pathologic bone loss. Debate persists as to the optimal void filler for this “limb salvage” surgery, whether metal or allograft bone. Clinicians focus on optimizing important functional gains for patients, and the risk of devastating implant infection has been thought to be similar regardless of implant material. Recent insights into infection pathophysiology are challenging this equipoise, however, with both basic science data suggesting a novel mechanism of infection of Staphylococcus aureus (the most common infecting agent) into the host lacunar–canaliculi network, and also clinical data revealing a higher rate of infection of allograft over metal. The current translational study was therefore developed to bridge the gap between these insights in a longitudinal murine model of infection of allograft bone and metal. Real-time Staphylococci infection characteristics were quantified in cortical bone vs metal, and both microarchitecture of host implant and presence of host immune response were assessed. An orders-of-magnitude higher bacterial burden was established in cortical allograft bone over both metal and cancellous bone. The establishment of immune-evading microabscesses was confirmed in both cortical allograft haversian canal and the submicron canaliculi network in an additional model of mouse femur bone infection. These study results reveal a mechanism by which Staphylococci evasion of host immunity is possible, contributing to elevated risks of infection in cortical bone. The presence of this local infection reservoir imparts massive clinical implications that may alter the current paradigm of osteomyelitis and bulk allograft infection treatment.

Background The dedifferentiated variant of chondrosarcoma is highly aggressive and carries an especially grim prognosis. While chemotherapeutics has failed to benefit patients with dedifferentiated chondrosarcoma significantly, preclinical chemosensitivity studies have been limited by a scarcity of available cell lines. There is, therefore, an urgent need to expand the pool of available cell lines. Methods We report the establishment of a novel dedifferentiated chondrosarcoma cell line DDCS2, which we isolated from the primary tumor specimen of a 60-year-old male patient. We characterized its short tandem repeat (STR) DNA profile, growth potential, antigenic markers, chemosensitivity, and oncogenic spheroid and colony-forming capacity. Results DDCS2 showed a spindle to polygonal shape and an approximate 60-hour doubling time. STR DNA profiling revealed a unique genomic identity not matching any existing cancer cell lines within the ATCC, JCRB, or DSMZ databases. There was no detectable contamination with another cell type. Western blot and immunofluorescence assays were consistent with a mesenchymal origin, and our MTT assay revealed relative resistance to conventional chemotherapeutics, which is typical of a dedifferentiated chondrosarcoma. Under ex vivo three-dimensional (3D) culture conditions, the DDCS2 cells produced spheroid patterns similar to the well-established CS-1 and SW1353 chondrosarcoma cell lines. Conclusion Our findings confirm DDCS2 is a novel model for dedifferentiated chondrosarcoma and therefore adds to the limited pool of current cell lines urgently needed to investigate the chemoresistance within this deadly cancer.

Adult pleomorphic rhabdomyosarcoma (RMS) is a rare and malignant mesenchymal tumor. Recently, we developed a patient-derived orthotopic xenograft (PDOX) model of adult pleomorphic RMS. In the present study, we evaluated the efficacy of tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R combined with caffeine (CAF) and valproic acid (VPA) on the adult RMS PDOX. An adult pleomorphic RMS cell line was established from the PDOX model. Cell survival after exposure to CAF and VPA was assessed, and the IC50 value was calculated for each drug. The RMS PDOX models were randomized into five groups: untreated control; tumor treated with cyclophosphamide (CPA); tumor treated with CAF + VPA; tumor treated with S. typhimurium A1-R; and tumor treated with S. typhimurium A1-R + CAF + VPA. Tumor size and body weight was measured twice a week. VPA caused a concentration-dependent cytocidal effect. A synergistic effect of combination treatment with CAF was observed against the RMS cell line. For the in vivo study, all treatments significantly inhibited tumor growth compared with the untreated control. S. typhimurium A1-R combined with VPA and CAF was significantly more effective than CPA, VPA combined with CAF, or S. typhimurium A1-R alone and significantly regressed the tumor volume compared with day 0. These results suggest that S. typhimurium A1-R together with VPA and CAF could regresses an adult pleomorphic RMS in a PDOX model and therefore has important future clinical potential.

Abstract Background Pleomorphic liposarcoma (PLPS) is a rare, heterogeneous and an aggressive variant of liposarcoma. Therefore, individualized therapy is urgently needed. Our recent reports suggest that trabectedin (TRAB) is effective against several patient-derived orthotopic xenograft (PDOX) mouse models. Here, we compared the efficacy of first-line therapy, doxorubicin (DOX), and TRAB in a platelet-derived growth factor receptor-α (PDGFRA)-amplified PLPS. Methods We used a fresh sample of PLPS tumor derived from a 68-year-old male patient diagnosed with a recurrent PLPS. Subcutaneous implantation of tumor tissue was performed in a nude mouse. After three weeks of implantation, tumor tissues were isolated and cut into small pieces. To match the patient a PDGFRA-amplified PLPS PDOX was created in the biceps femoris of nude mice. Mice were randomized into three groups: Group 1 (G1), control (untreated); Group 2 (G2), DOX-treated; Group 3 (G3), TRAB-treated. Measurement was done twice a week for tumor width, length, and mouse body weight. Results The PLPS PDOX showed resistance towards DOX. However, TRAB could arrest the PLPS (p

Bone sarcomas are a collection of sporadic malignancies of mesenchymal origin. The most common subtypes include osteosarcoma, Ewing sarcoma, chondrosarcoma, and chordoma. Despite the use of aggressive treatment protocols consisting of extensive surgical resection, chemotherapy, and radiotherapy, outcomes have not significantly improved over the past few decades for osteosarcoma or Ewing sarcoma patients. In addition, chondrosarcoma and chordoma are resistant to both chemotherapy and radiation therapy. There is, therefore, an urgent need to elucidate which novel new therapies may affect bone sarcomas. Emerging checkpoint inhibitors have generated considerable attention for their clinical success in a variety of human cancers, which has led to works assessing their potential in bone sarcoma management. Here, we review the recent advances of anti-PD-1/PD-L1 and anti-CTLA-4 blockade as well as other promising new immune checkpoint targets for their use in bone sarcoma therapy. Keywords: Immune checkpoint, Immunotherapy, Bone sarcoma, Anti-PD-1/PD-L1, Anti-CTLA-4

Background: Access to accurate and complete medication histories across healthcare institutions enables effective patient care. Histories across healthcare institutions currently rely on centralized systems for sharing medication data. However, there is a lack of efficient mechanisms to ensure that medication histories transferred from one institution to another are accurate, secure, and trustworthy. Methods: In this article, we introduce a decentralized medication management system (DMMS) that leverages the advantages of blockchain to manage medication histories. DMMS is realized as a decentralized network under the hyperledger fabric framework. Based on the network, we designed an architecture, within which each prescriber can create prescriptions for each patient and perform queries about historical prescriptions accordingly. Finally, we analyzed the advantages of DMMS over centralized systems in terms of accuracy, security, trustworthiness, and privacy. Results: We developed a proof of concept to showcase DMMS. In this system, a prescriber prescribes medications for a patient and then encrypts the prescriptions via the patient’s public keys. Patients can query their own prescriptions from different histories across healthcare institutions and then decrypt the prescriptions via their private keys. At the same time, a prescriber can query a patient’s prescription records across healthcare institutions after approval from the patient. Analytic results show that DMMS can improve security, trustworthiness, and privacy in medication history sharing and exchanging across healthcare institutions. In addition, we discuss the potential for DMMS in e-prescribing markets. Conclusions: This study shows that a distributed secure ledger can enable reliable, interoperable, and accurate medication history sharing. Keywords: Blockchain Ledger, Decentralized, Hyperledger Fabric Framework, Medication Histories Please see a related Letter to the Editor (https://doi.org/10.30953/bhty.v2.98), and its response (https://doi.org/10.30953/bhty.v2.108)

Gastrointestinal stromal tumor (GIST) is a refractory disease in need of novel efficacious therapy. The aim of our study was to evaluate the effectiveness of tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R) using on a patient derived orthotopic xenograft (PDOX) model of imatinib-resistant GIST. The GIST was obtained from a patient with regional recurrence, and implanted in the anterior gastric wall of nude mice. The GIST PDOX mice were randomized into 3 groups of 6 mice each when the tumor volume reached 60 mm3: G1, control group; G2, imatinib group (oral administration [p.o.], daily, for 3 weeks); G3, S. typhimurium A1-R group (intravenous [i.v.] injection, weekly, for 3 weeks). All mice from each group were sacrificed on day 22. Relative tumor volume was estimated by laparotomy on day 0 and day 22. Body weight of the mouse was evaluated 2 times per week. We found that S. typhimurium A1-R significantly reduced tumor growth in contrast to the untreated group (P = 0.001). In addition, we found that S. typhimurium A1-R was more effective compared to imatinib (P = 0.013). Furthermore, Imatinib was not significantly effective compared to the control group (P = 0.462). These results indicate that S. typhimurium A1-R may be new effective therapy for imatinib-resistant GIST and therefore a good candidate for clinical development of this disease.

The lubrication of the cartilaginous structures in human joints is provided by a fluid from a specialized layer of cells at the surface of a delicate tissue called the synovial lining. Little is known about the characteristics of the fluids produced after a joint arthroplasty procedure. A literature review was carried out to identify papers that characterized the synovial lining and the synovial fluids formed after total hip or knee arthroplasty. Five papers about synovial lining histology and six papers about the lubricating properties of the fluids were identified. The cells making up the re-formed synovial lining, as well as the lining of interface membranes, were similar to the typical Type A and B synoviocytes of normal joints. The synovial fluids around joint replacement devices were typically lower in viscosity than pre-arthroplasty fluids but the protein concentration and phospholipid concentrations tended to be comparable, suggesting that the lining tissue function was preserved after arthroplasty. The widespread, long-term success of joint arthroplasty suggests that the lubricant formed from implanted joint synovium is adequate for good clinical performance in the majority of joints. The role the fluid plays in component wear or failure is a topic for future study.