Breaking through Multiple Myeloma: A Paradigm for a Comprehensive Tumor Ecosystem Targeting.

Multiple myeloma (MM) is a cancerous condition characterized by the proliferation of plasma cells within the hematopoietic marrow, resulting in multiple osteolytic lesions. MM patients typically experience bone pain, kidney damage, fatigue due to anemia, and infections. Historically, MM was an incurable disease with a life expectancy of around three years after diagnosis. However, over the past two decades, the development of novel therapeutics has significantly improved patient outcomes, including response to treatment, remission duration, quality of life, and overall survival. These advancements include thalidomide and its derivatives, lenalidomide and pomalidomide, which exhibit diverse mechanisms of action against the plasma cell clone. Additionally, proteasome inhibitors such as bortezomib, ixazomib, and carfilzomib disrupt protein degradation, proving specifically toxic to cancerous plasma cells. Recent advancements also involve monoclonal antibodies targeting surface antigens, such as elotuzumab (anti-CS1) and daratumumab (anti-CD38), bispecific t-cell engagers such as teclistamab (anti-BCMA/CD3) and Chimeric antigen receptor T (CAR-T)-based strategies, with a growing focus on drugs that exhibit increasingly targeted action against neoplastic plasma cells and relevant effects on the tumor microenvironment.

High-Risk Multiple Myeloma: Integrated Clinical and Omics Approach Dissects the Neoplastic Clone and the Tumor Microenvironment.

Multiple myeloma (MM) is a genetically heterogeneous disease that includes a subgroup of 10-15% of patients facing dismal survival despite the most intensive treatment. Despite improvements in biological knowledge, MM is still an incurable neoplasia, and therapeutic options able to overcome the relapsing/refractory behavior represent an unmet clinical need. The aim of this review is to provide an integrated clinical and biological overview of high-risk MM, discussing novel therapeutic perspectives, targeting the neoplastic clone and its microenvironment. The dissection of the molecular determinants of the aggressive phenotypes and drug-resistance can foster a better tailored clinical management of the high-risk profile and therapy-refractoriness. Among the current clinical difficulties in MM, patients' management by manipulating the tumor niche represents a major challenge. The angiogenesis and the stromal infiltrate constitute pivotal mechanisms of a mutual collaboration between MM and the non-tumoral counterpart. Immuno-modulatory and anti-angiogenic therapy hold great efficacy, but variable and unpredictable responses in high-risk MM. The comprehensive understanding of the genetic heterogeneity and MM high-risk ecosystem enforce a systematic bench-to-bedside approach. Here, we provide a broad outlook of novel druggable targets. We also summarize the existing multi-omics-based risk profiling tools, in order to better select candidates for dual immune/vasculogenesis targeting.

Results of 200 Consecutive Ceramic-on-Ceramic Cementless Hip Arthroplasties in Patients Up To 50 Years of Age: A 5-24 Years of Follow-Up Study.

BACKGROUND: Ceramic-on-ceramic (CoC) bearings due to their mechanical properties can be used in primary total hip arthroplasty (THA) especially in young patients requiring a long-lasting implant. The goal of this study is to analyze the results of a series of 200 consecutive CoC THAs in patients aged 50 years or less at the time of surgery. METHODS: A retrospective study was conducted on the first 200 consecutive CoC arthroplasties performed using the direct lateral approach on 105 females and 81 males (14 bilateral cases) with an average age of 44.2 (16-50) years. The diagnosis was primary or post-traumatic osteoarthritis in 94 cases, avascular necrosis of the femoral head in 47, displaced intracapsular femoral neck fracture in 29, osteoarthritis secondary to developmental dysplasia of the hip/Legg-Calvè-Perthes disease/slipped capital femoral epiphysis in 20, and rheumatic diseases in 10 cases. The preoperative Harris Hip Score was 32.5 on average (range 15-55). All the implants were cementless. In 177 THAs the coupling was alumina-on-alumina, and in 23 cases the coupling was AMC-on-AMC (alumina matrix composite). RESULTS: Twenty-five patients with 28 THAs were lost at the final follow-up, 2 stems were revised due to subsidence, 1 cup was revised due to malposition, 1 femoral head was changed because of impingement, and 1 THA was revised for periprosthetic infection. Three patients sustained a Vancouver B1 periprosthetic femoral fracture. At the final follow-up (mean 14.9 years; minimum 5 years to maximum 24 years), 172 THAs were eligible for clinical and radiographic evaluation: none was revised for wear and/or breakage of the ceramic components. Harris Hip Score rose up to a mean value of 90.1 (52-100). CONCLUSION: The present report demonstrates that CoC coupling offers excellent long-term results in THA performed in young patients with very low wear and no adverse effects caused by the material.

The fake unlocked femoral nail: A configuration to avoid in stable pertrochanteric femur fractures.

BACKGROUND: Intramedullary unlocked nailing is a safe and used treatment for stable pertrocantheric fractures. Due to the femoral anterior bow of the shaft or a wrong entry point, the distal tip of the nail can be impinging the anterior cortex. This type of situation can compromise the function of the nail, leading to nonunion of the fracture, and cut-out. The aim of this study was to assess the relationship between nail impingement of the anterior cortex of the femur and cut-out and nonunion incidence in patients with pertrochanteric stable fracture treated with an IM nail in an unlocked configuration. MATERIAL AND METHODS: A retrospective study based on medical records and imaging from the archives of our Level I academic medical center was conducted. The study included patients with proximal femoral fractures treated with short cephalomedullary nails between January 2012 and May 2015. The data collected were analyzed to a possible correlation with the healing time and occurrence of nonunion and cut-out. RESULTS: The study population counted 429 cases. Applying the inclusion criteria the final series was composed of 169 patients: 112 females (66.73%) and 57 males (33.27%), with a mean age of 81.23 years (range: 67-93 years). Distal tip impingement was observed in 22 cases (13.02%). In total 16 (9.47%) postoperative complications were recorded: 8 non-union and 7 cut-outs. Consolidation was registered in 153 cases and the fracture healing time averaged 14.4 ± 3.8 weeks (range, 11-24 weeks). The cortical impingement was correlated with nonunion and cut-out (p < 0.001) Logistic regression analysis revealed jamming sign significantly affected the fracture healing time (p < 0.001). CONCLUSION: The occurrence of cut-out and nonunion after cephalomedullary nailing of stable pertrochanteric fractures appear to be correlated to the presence of the cortical impingement. For this reason, the fake unlocked femoral nail with the cortical impingement is a configuration to avoid in stable pertrochanteric femur fractures.