IMPORTANCE Despite improvements in survival with aggressive chemoradiation, outcomes for patients diagnosed as having glioblastoma multiforme (GBM) remain poor. Survival is further limited in elderly patients, who are often unable to tolerate multimodality therapy. The appropriate treatment approach for elderly patients (aged >65 years) with GBM remains unclear. While the literature supports the use of standard radiotherapy (60 Gy), several recent studies have suggested that treatment with temozolomide monotherapy or short-course radiotherapy may be a reasonable alternative. OBJECTIVE To review literature reporting survival data related to treatment of elderly patients with GBM using either temozolomide alone or radiotherapy alone. EVIDENCE REVIEW We performed a systematic review to identify articles from the temozolomide era (2005-present) that reported survival data related to treatment of elderly patients with GBM using either temozolomide alone or radiotherapy alone, with consideration of O 6-methylguanine-DNA-methyltransferase gene (MGMT) promoter methylation status. PubMed was searched for articles between January 1, 2005, and August 31, 2013, using the search terms glioblastoma, elderly, temozolomide, radiation, hypofractionated, and survival, and references from relevant articles were searched. Selected articles reported overall survival data associated with either temozolomide alone or radiotherapy alone in elderly patients (aged Ն60 years) with GBM; articles were excluded if they did not report survival data from radiotherapy alone or temozolomide alone, were not restricted to an elderly population, did not report original data, were not restricted to patients with primary GBM, were a subgroup analysis of a prior article, were a case report, or could not be located in entirety. Articles were interrogated as per the criteria designated by the Oxford Centre for Evidence-Based Medicine to determine the level of evidence presented, and data from level 1 and 2 studies were used for analysis. From a review of 185 articles, 23 were selected for inclusion and final analysis. From these, we identified 2 level 1 studies and 1 level 2 study that reported overall survival in elderly patients treated with temozolomide alone, and 4 level 1 studies and 2 level 2 studies that reported overall survival in elderly patients treated with radiotherapy alone. FINDINGS This review of the literature revealed several limitations. First, there is a paucity of randomized clinical studies comparing temozolomide alone with radiotherapy alone in elderly patients with GBM. Second, there is a lack of coherence in the literature for the definition of elderly. Third, the treatment paradigms used are not consistent from study to study. Regardless, the available data did allow the formulation of a recommendation based on level 1 and 2 data. CONCLUSIONS AND RELEVANCE The literature supports the use of hypofractionated radiotherapy or temozolomide monotherapy in the treatment of elderly patients with GBM. In patients with MGMT promoter meth...

B cell acute lymphoblastic leukemia (B-ALL) is frequently associated with mutations or chromosomal translocations of genes encoding transcription factors. Conditional deletion of genes encoding the E26-transformation–specific transcription factors, PU.1 and Spi-B, in B cells (ΔPB mice) leads to B-ALL in mice at 100% incidence rate and with a median survival of 21 wk. We hypothesized that PU.1 and Spi-B may redundantly activate transcription of genes encoding tumor suppressors in the B cell lineage. Characterization of aging ΔPB mice showed that leukemia cells expressing IL-7R were found in enlarged thymuses. IL-7R–expressing B-ALL cells grew in culture in response to IL-7 and could be maintained as cell lines. Cultured ΔPB cells expressed reduced levels of B cell linker protein (BLNK), a known tumor suppressor gene, compared with controls. The Blnk promoter contained a predicted PU.1 and/or Spi-B binding site that was required for promoter activity and occupied by PU.1 and/or Spi-B as determined by chromatin immunoprecipitation. Restoration of BLNK expression in cultured ΔPB cells opposed IL-7–dependent proliferation and induced early apoptosis. We conclude that the tumor suppressor BLNK is a target of transcriptional activation by PU.1 and Spi-B in the B cell lineage.

Aims Iliac wing (Type I) and iliosacral (Type I/IV) pelvic resections for a primary bone tumour create a large segmental defect in the pelvic ring. The management of this defect is controversial as the surgeon may choose to reconstruct it or not. When no reconstruction is undertaken, the residual ilium collapses back onto the remaining sacrum forming an iliosacral pseudarthrosis. The aim of this study was to evaluate the long-term oncological outcome, complications, and functional outcome after pelvic resection without reconstruction. Methods Between 1989 and 2015, 32 patients underwent a Type I or Type I/IV pelvic resection without reconstruction for a primary bone tumour. There were 21 men and 11 women with a mean age of 35 years (15 to 85). The most common diagnosis was chondrosarcoma (50%, n = 16). Local recurrence-free, metastasis-free, and overall survival were assessed using the Kaplan-Meier method. Patient function was evaluated using the Musculoskeletal Tumour Society (MSTS) and Toronto Extremity Salvage Score (TESS). Results At a mean follow-up of 159 months (1 to 207), 23 patients were alive without disease, one was alive with lung metastases, one was alive following local recurrence, four were dead of disease, and three had died from other causes. The overall ten-year survival was 77%. There was only one (3%) local recurrence, which occurred at 26 months. There were 18 complications in 17 patients; 13 wound healing complications/infections, three fractures, one pulmonary embolism, and one dislocation of the hip. Most complications occurred early. The mean functional scores were 21.1 (SD 8.1) for MSTS-87, 67.3 (SD 23.9) for MSTS-93 and 76.2 (SD 20.6) for TESS. Conclusion Patients requiring Type I or Type I/IV pelvic resections can expect a good oncological outcome and a high rate of local control. Complications are generally acute in nature and are easily manageable. These patients achieved a good functional outcome without the need for bony reconstruction. Cite this article: Bone Joint J 2020;102-B(6):779–787.

Background:Heterotopic ossification (HO) following acetabular fractures is a common complication that may affect clinical outcomes. However, the effects of prophylactic treatment with nonsteroidal anti-inflammatory drugs or radiation therapy remain controversial. While several factors have been related to the development of HO, there is considerable uncertainty regarding their importance or effect size in the setting of acetabular surgery. Therefore, this systematic review aims to summarize the risk factors for HO following the operative fixation of acetabular fractures and clarify their interrelationships.Methods:In accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, PubMed, MEDLINE, Embase, and CINAHL databases were searched from inception to February 2021. Studies that assessed factors related to HO development among patients with operatively repaired acetabular fractures were included. Outcomes were risk factors and their effect size (p values, odds ratios, and 95% confidence intervals).Results:Twenty-five studies and 1 conference abstract with a total of 3,940 patients were included. The following risk factors for HO were identified. Patient factors were increased body mass index, male sex, and increased age. Injury factors were intensive care unit (ICU) admission and length of stay, non-ICU hospitalization for >10 days, the need for mechanical ventilation for ≥2 days, abdominal and/or chest injuries, the number and type of associated fractures, traumatic brain injuries, T-type acetabular fractures, pelvic ring injuries, and hip dislocation. Care factors were a delay to surgery, extensile and posterior surgical approaches to the hip, trochanteric osteotomy, postoperative step-off of >3 mm, and a delay to prophylaxis following injury or surgery. Ethnicity, Injury Severity Score, cause of the fracture, femoral head injuries, degloving injuries, comminution, intra-articular debris, the type of bone void filler, gluteus minimus muscle preservation, prolonged operative time, and intraoperative patient position were not risk factors for developing HO.Conclusions:HO following operative fixation of acetabular fractures is not uncommon, with severe-grade HO associated with substantial disability. Careful consideration of the risk factor effect sizes and interdependencies could aid physicians in identifying patients at risk for developing HO and guide their prophylactic management. The results of this study could establish a framework for future studies.Level of Evidence:Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.