The evolving characterization of the biological basis of adamantinomatous craniopharyngioma (ACP) has provided insights critical for novel systemically delivered therapies. While current treatment strategies for ACP are associated with low mortality rates, patients experience severely lowered quality of life due to high recurrence rates and chronic sequelae, presenting a need for novel effective treatment regimens. The identification of various dysregulated pathways that play roles in the pathogenesis of ACP has prompted the investigation of novel treatment options. Aberrations in the CTNNB1 gene lead to the dysregulation of the Wnt pathway and the accumulation of nuclear β-catenin, which may play a role in tumor invasiveness. While Wnt pathway/β-catenin inhibition may be a promising treatment for ACP, potential off-target effects have limited its use in current intervention strategies. Promising evidence of the therapeutic potential of cystic proinflammatory mediators and immunosuppressants has been translated into clinical therapies, including interleukin 6 and IDO-1 inhibition. The dysregulation of the pathways of mitogen-activated protein kinase/extracellular signal–regulated kinase (MAPK/ERK), epidermal growth factor receptor (EGFR), and programmed cell death protein 1 and its ligand (PD-1/PD-L1) has led to identification of various therapeutic targets that have shown promise as clinical strategies. The Sonic Hedgehog (SHH) pathway is upregulated in ACP and has been implicated in tumorigenesis and tumor growth; however, inhibition of SHH in murine models decreased survival, limiting its therapeutic application. While further preclinical and clinical data are needed, systemically delivered therapies could delay or replace the need for more aggressive definitive treatments. Ongoing preclinical investigations and clinical trials of these prospective pathways promise to advance treatment approaches aimed to increase patients’ quality of life.

Bacteremia is a leading cause of death in sub-Saharan Africa where childhood mortality rates are the highest in the world. The early diagnosis of bacteremia and initiation of treatment saves lives, especially in high-disease burden areas. However, diagnosing bacteremia is challenging for clinicians, especially in children presenting with co-infections such as malaria and HIV. There is an urgent need for a rapid method for detecting bacteremia in pediatric patients with co-morbidities to inform treatment. In this manuscript, we have developed and clinically validated a novel method for the direct detection of amphiphilic pathogen biomarkers indicative of bacteremia, directly in aqueous blood, by mimicking innate immune recognition. Specifically, we have exploited the interaction of amphiphilic pathogen biomarkers such as lipopolysaccharides (LPS) from Gram-negative bacteria and lipoteichoic acids (LTA) from Gram-positive bacteria with host lipoprotein carriers in blood, in order to develop two tailored assays – lipoprotein capture and membrane insertion – for their direct detection. Our assays demonstrate a sensitivity of detection of 4 ng/mL for LPS and 2 ng/mL for LTA using a waveguide-based optical biosensor platform that was developed at LANL. In this manuscript, we also demonstrate the application of these methods for the detection of LPS in serum from pediatric patients with invasive Salmonella Typhimurium bacteremia (n = 7) and those with Staphylococcal bacteremia (n = 7) with 100% correlation with confirmatory culture. Taken together, these results demonstrate the significance of biochemistry in both our understanding of host-pathogen biology, and development of assay methodology, as well as demonstrate a potential new approach for the rapid, sensitive and accurate diagnosis of bacteremia at the point of need.

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OBJECTIVEHealth policy changes have led to increased emphasis on value-based care to improve resource utilization and reduce inpatient hospital length of stay (LOS). Recently, LOS has become a major determinant of quality of care and resource utilization. For adolescent idiopathic scoliosis (AIS), the determinants of extended LOS after elective posterior spinal fusion (PSF) remain relatively unknown. In the present study, the authors investigated the impact of patient and hospital-level risk factors on extended LOS following elective PSF surgery (≥ 4 levels) for AIS.METHODSThe Kids’ Inpatient Database (KID) was queried for the year 2012. Adolescent patients (age range 10–17 years) with AIS undergoing elective PSF (≥ 4 levels) were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification coding system. Extended hospital LOS was defined as greater than the 75th percentile for the entire cohort (> 6 days), and patients were dichotomized as having normal LOS or extended LOS. Patient demographics, comorbidities, complications, LOS, discharge disposition, and total cost were recorded. A multivariate logistic regression model was used to determine the odds ratio for risk-adjusted LOS. The primary outcome was the degree to which patient comorbidities or postoperative complications correlated with extended LOS.RESULTSComorbidities were overall significantly higher in the extended-LOS cohort than the normal-LOS cohort. Patients with extended LOS had a significantly greater proportion of blood transfusion (p < 0.001) and ≥ 9 vertebral levels fused (p < 0.001). The overall complication rates were greater in the extended-LOS cohort (20.3% [normal-LOS group] vs 43.5% [extended-LOS group]; p < 0.001). On average, the extended-LOS cohort incurred $18,916 more in total cost than the normal-LOS group ($54,697 ± $24,217 vs $73,613 ± $38,689, respectively; p < 0.001) and had more patients discharged to locations other than home (p < 0.001) than did patients in the normal-LOS cohort. On multivariate logistic regression, several risk factors were associated with extended LOS, including female sex, obesity, hypertension, fluid electrolyte disorder, paralysis, blood transfusion, ≥ 9 vertebrae fused, dural injury, and nerve cord injury. The odds ratio for extended LOS was 1.95 (95% CI 1.50–2.52) for patients with 1 complication and 5.43 (95% CI 3.35–8.71) for patients with > 1 complication.CONCLUSIONSThe authors’ study using the KID demonstrates that patient comorbidities and intra- and postoperative complications all contribute to extended LOS after spinal fusion for AIS. Identifying multimodality interventions focused on reducing LOS, bettering patient outcomes, and lowering healthcare costs are necessary to improve the overall value of care for patients undergoing spinal fusion for AIS.

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