Using procalcitonin to guide antimicrobial duration in sepsis: asking the same questions will not bring different answers

In the previous issue of Critical Care, Dr Bellomo and colleagues reported an observational study of the relationship between nutritional intake and survival in the RENAL randomized controlled trial. In summary, the total energy intake in a very large and severely ill patient population was low. Higher average daily caloric energy intake was not associated with improved survival. The study illustrates the complexity of the interaction between disease and nutrition.     

Percutaneous transhepatic choledochoenterostomy in a patient with a biliary obstruction

A needle guide was used to create a fistula from an obstructed common bile duct to the duodenum in a patient with a large tumor of the head of the pancreas. The tortuosity and severity of the stricture prevented the use of routine guide wire passage. A 5-F hyperalimentation catheter was also placed, in addition to the biliary drainage stent.     

Neuroradiographic changes following convection-enhanced delivery of the recombinant cytotoxin interleukin 13-PE38QQR for recurrent malignant glioma

OBJECT: Convection-enhanced delivery (CED) is a novel method for delivering therapeutic agents to infiltrative brain tumor cells. For agents administered by CED, changes on magnetic resonance (MR) imaging directly resulting from catheter placement, infusion, and the therapeutic compound may confound any interpretation of tumor progression. As part of an ongoing multiinstitutional Phase I study, 14 patients with recurrent malignant glioma underwent CED of interleukin (IL) 13-PE38QQR, a recombinant cytotoxin consisting of human IL-13 conjugated with a truncated Pseudomonas exotoxin. Serial neuroradiographic changes were assessed in this cohort of patients. METHODS: Patients were treated in two groups: Group 1 patients received IL13-PE38QQR before and after tumor resection; Group 2 patients received infusion only after tumor resection. Preoperative and postinfusion MR images were obtained prospectively at specified regular intervals. Changes were noted along catheter tracks on postresection MR images obtained in all patients. A simple grading system was developed to describe these changes. When MR imaging changes appeared to be related to IL1 3-PE38QQR, patients were followed up without instituting new antitumor therapy. CONCLUSIONS: As CED of therapeutic agents becomes more common, clinicians and investigators must become aware of associated neuroimaging changes that should be incorporated into toxicity assessment. We have developed a simple grading system to facilitate communication about these changes among investigators. Biological imaging modalities that could possibly distinguish these changes from recurrent tumor should be evaluated. In this study the authors demonstrate the challenges in determining efficacy when surrogate end points such as time to tumor progression as defined by new or progressive contrast enhancement on MR imaging are used with this treatment modality.     

Patterns of care for adults with newly diagnosed malignant glioma

Context  Patients with malignant glioma (grade III or IV) face a poor prognosis, and few evidence-based treatment guidelines are available. There is a dearth of prospective data on patterns of care for these patients. Objective  To provide benchmark data to enable comparison of individual practice patterns and outcomes. Design, Setting, and Patients  The Glioma Outcomes (GO) Project enrolled 788 patients at 52 clinical sites, both academic and community practices, between December 1997 and July 2000. The enrollment criteria included adult patients with primary grade III or IV glioma undergoing a first or second operation for diagnosis or treatment. The data collection instruments included questionnaire forms given at enrollment, during the perioperative period, and at follow-up intervals of 3 months until death or a maximum of 24 months. Of the patients recorded in the GO database, 565 patients with newly diagnosed tumors were used for this analysis. Main Outcome Measures  Patterns of care (surgical management, perioperative care, postoperative management). Results  Most patients underwent magnetic resonance imaging (n = 518; 92%) and an attempt at tumor resection (n = 425; 75%). Cortical mapping (n = 107; 19%) and intraoperative image guidance (n = 161; 29%) were uncommon. Most received perioperative corticosteroids (n = 535; 99%) and antiepileptic medications (n = 497; 88%), but few received antidepressants (n = 38; 8%) or prophylactic heparin (n = 42; 7%). Most received adjuvant radiation therapy (n = 479; 87%), but fewer received chemotherapy (n = 300; 54%). Practice patterns varied significantly between academic and community settings. Conclusions  Reliance on magnetic resonance imaging, surgery, and radiation is generally accepted; however, relatively infrequent chemotherapy use may conflict with published literature, and frequent use of prophylactic antiepileptic medications contradicts established practice guidelines. Other practice patterns involving surgical adjuncts, prophylactic heparin, and antidepressants require further investigation to clarify appropriateness. Establishing further clinical guidelines may help reduce variability in practice patterns.      

Patterns of care and treatment outcomes in older adults with low grade glioma: a 50-year experience

The purpose of this study was to identify changes in presentation, treatment and outcomes of older patients with low-grade glioma (LGG) over the past 50 years. 94 adults aged 55 or older upon diagnosis of a WHO grade II LGG at Mayo Clinic between 1960 and 2011 were included and grouped by those diagnosed before (group I: 1960–1989) and after (group II: 1990–2011) the routine use of post-operative MRI. Median follow-up was 11.4 years. Pathologic diagnoses included astrocytoma in 55%, mixed oligoastrocytoma in 18% and oligodendroglioma in 27%. Gross total resection (GTR) was achieved in 10%, radical subtotal resection (rSTR) in 6%, subtotal resection (STR) in 20% and biopsy only in 64%. Post-operative radiotherapy (PORT) was given in 77%. More patients in the modern era received GTR/rSTR (20 vs. 7%), though the difference was not statistically significant. Median progression-free survival (PFS) was 3.0 years, with 5- and 10-year PFS rates of 31 and 10%, respectively. Median, 5- and 10-year overall survival (OS) was 4.1 years, 43 and 17%, respectively. PFS and OS did not improve in the modern era. Factors negatively associated with PFS on multivariate analysis included astrocytoma histology, contrast enhancement and STR/biopsy. Factors associated with poor OS on multivariate analysis included astrocytoma histology, deep location, contrast enhancement and STR/biopsy. Despite reports of improving outcomes for younger patients treated in the modern era, outcomes have not significantly improved for older patients. Further efforts to improve outcomes based on molecular genotyping are needed to determine a rational strategy for treatment intensification.     

Oligodendroglioma cell lines containing t(1;19)(q10;p10)

Investigating the biology of oligodendroglioma and its characteristic combined deletion of chromosomal arms 1p and 19q, mediated by an unbalanced translocation, t(1;19)(q10;p10), has been hampered by the lack of cell lines that harbor these traits. We grew cells from 2 anaplastic oligodendrogliomas in serum-free conditions. Serial propagation and expansion led to the establishment of permanent cell lines that maintained the genetic signature of the parent oligodendrogliomas and displayed features of brain tumor stem cells in vitro. One line was established from a treatment-naïve tumor and the other from a temozolomide resistant recurrent tumor. These lines may be important tools for understanding the biology of oligodendrogliomas and the function of their defining genetic traits.     

C-reactive protein in community-acquired sepsis: you can teach new tricks to an old dog

Severe sepsis is a major challenge for clinicians caring for acutely ill patients. For many years, several biomarkers have been tested and proposed to improve the ability not only to diagnose but also to anticipate clinical response to antibiotics. Despite the availability of many sophisticated and novel biomarkers, current evidence demonstrates that C-reactive protein (CRP), a well-known and relatively inexpensive biomarker, is useful in the clinical setting. The sequential evaluation of plasma CRP concentrations in patients with severe sepsis and the interpretation of its patterns may allow assessments of individual prognosis and response to treatment.     

A deep learning model for discriminating true progression from pseudoprogression in glioblastoma patients

Journal of Neuro-Oncology - Glioblastomas (GBMs) are highly aggressive tumors. A common clinical challenge after standard of care treatment is differentiating tumor progression from...