CXCR4, a cell surface chemokine receptor, mediates cellular dissemination, invasion, and proliferation in a wide range of cancers including gliomas. It is over-expressed in glioma progenitor cells, and its protein ligand, CXCL12, has been shown to mediate a specific proliferative response in these cells thereby implicating a role for CXCR4 in glioma initiation and renewal. Given the failure of currently employed therapies to meaningfully impact prognosis in patients with high-grade gliomas, the CXCR4-CXCL12 axis represents a novel biologically relevant mechanism that could be specifically targeted for therapy. From this perspective, this review summarizes the biological effects of CXCR4 activity and its implications for glioma pathogenesis. Ultimately, the development of effective treatment approaches for malignant glioma must be based on a rational mechanistic understanding of tumor cell biology. As such, this article presents such a framework with regard to the CXCR4 pathway in glioma thereby supporting the further investigation of CXCR4 as a therapeutic target in patients with this disease.

We evaluated the incidence and risk factors for hypogammaglobulinemia after allogeneic hematopoietic SCT (HSCT) in pediatric patients. Ig levels were measured pre-transplant, every 2 weeks until day 100 and then monthly post SCT in 185 patients undergoing myeloablative HSCT. Median age was 9 years; 142 (77%) had malignant disease and 114 (62%) received stem cells from an unrelated source. Hypogammaglobulinemia (IgG o500 mg/dL) developed in 143 (77%) of the patients at a median of 56 days (range 15-339) post SCT. The cumulative incidence of hypogammaglobulinemia at 1 year was higher among patients who developed acute GVHD (97% vs 54%, Po0.001), and for those receiving stem cells from an unrelated source (94% vs 51%, Po0.001). The cumulative incidence of TRM was significantly higher for patients with hypogammaglobulinemia (P ¼ 0.026). In multivariable analysis, lower pre-transplant IgG level (Po0.001), younger age (P ¼ 0.012), diagnosis of malignant disease (Po0.001), receiving unrelated SCT (Po0.001) and development of acute GVHD (Po0.001) were all significantly associated with higher risk of hypogammaglobulinemia post HSCT. We conclude that hypogammaglobulinemia is common, following allogeneic HSCT in pediatric patients, especially in those with malignant diseases, those who receive an unrelated transplant or patients who develop GVHD. Keywords: hypogammaglobulinemia; allo-SCT; children; IVIG; IgG; GVHD INTRODUCTION Hematopoietic SCT (HSCT) is an established therapy for various malignant and non-malignant disorders in children. The recovery of the immune system after allogeneic HSCT depends on multiple variables including preparative regimen, age and the presence of GVHD. 1 In a study of 93 adult patients, the number of B cell precursors in the BM 1-year post transplant was significantly lower in patients with chronic GVHD. Neither the CD34 þ cell dose, stem cell source (BM vs peripheral blood), donor or patient age were associated with B cell recovery. 2 In another study, low immunoglobulin levels have been associated with decreased survival and increased TRM in adult patients post allogeneic HSCT. In this study, factors associated with low IgG level were age o30 years, female donor to male recipient, not receiving antithymocyte globulin in the preparative regimen and the GVHD prophylaxis regimen. 3 The authors reported a decreased survival and increased TRM in these patients. The slow recovery of immune function post SCT has been linked to poor thymic function. 4 Pediatric patients have more intact thymic function compared with adult patients, which may influence the recovery of B cell function following HSCT. Unlike adult patients, one-third of the pediatric patients undergo an allogeneic HSCT for diseases other than malignancy. Except for patients with primary immune deficiency, those patients have generally an intact immune system prior to transplant. There are no published studies examining the incidence and risk factors for hypogammaglobulinemia post myeloablative allogeneic HSCT in pediatric patients.

Background:Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) versus open TLIF, addressing lumbar degenerative disc disease (DDD) or grade I spondylolisthesis (DS), are associated with shorter hospital stays, decreased blood loss, quicker return to work, and equivalent short- and long-term outcomes. However, no prospective study has assessed whether the extent of intraoperative muscle trauma utilizing creatinine phosphokinase levels (CPK) differently impacts long-term outcomes.Methods:Twenty-one patients underwent MIS-TLIF (n = 14) versus open-TLIF (n = 7) for DDD or DS. Serum CPK levels were measured at baseline, and postoperatively (days 1, 7, and 1.5, 3 and 6 months). The correlation between the extent of intraoperative muscle trauma and two-year improvement in functional disability was evaluated (multivariate regression analysis). Additionally, baseline and two-year changes in Visual Analog Scale (VAS)-leg pain (LP), VAS-back pain (BP), Oswestry Disability Index (ODI), Short-Form-36 (SF-36) Physical Component Score (PCS) and SF-36 Mental Component Score (MCS), and postoperative satisfaction with surgical care were assessed.Results:Although the mean change from baseline in the serum creatine phosphokinase level on POD 1 was greater for MIS-TLIF (628.07) versus open-TLF (291.42), this did not correlate with lesser two-year improvement in functional disability. Both cohorts also showed similar two-year improvement in VAS-LP, ODI, and SF-36 PCS/MCS.Conclusion:Increased intraoperative muscle trauma unexpectedly observed in higher postoperative CPK levels for MIS-TLIF versus open-TLIF did not correlate with any differences in two-year improvement in pain and functional disability.

Study Design: Review. Objective: A comparative overview of cost-effectiveness between minimally invasive versus and equivalent open spinal surgeries. Methods: A literature search using PubMed was performed to identify articles of interest. To maximize the capture of studies in our initial search, we combined variants of the terms “cost,” “minimally invasive,” “spine,” “spinal fusion,” “decompression” as either keywords or MeSH terms. PearlDiver database was queried for open and minimally invasive surgery (MIS; endoscopic or percutaneous) reimbursements between Q3 2015 and Q2 2018. Results: In general, MIS techniques appeared to decrease blood loss, shorten hospital lengths of stay, mitigate complications, decrease perioperative pain, and enable quicker return to daily activities when compared to equivalent open surgical techniques. With regard to cost, primarily as a result of these latter benefits, MIS was associated with lower costs of care when compared to equivalent open techniques. However, cost reporting was sparse, and relevant methodology was inconsistent throughout the spine literature. Within the PearlDiver data sets, MIS approaches had lower reimbursements than open approaches for both lumbar posterior fusion and discectomy. Conclusions: Current data suggests that overall cost-savings may be incurred with use of MIS techniques. However, data reporting on costs lacks in uniformity, making it difficult to formulate any firm conclusions regarding any incremental improvements in cost-effectiveness that may be incurred when utilizing MIS techniques when compared to equivalent open techniques.