Glioblastoma is the most common malignant brain tumor, and it carries an extremely poor prognosis. Attempts to develop targeted therapies have been hindered because the blood-brain barrier prevents many drugs from reaching tumors cells. Furthermore, systemic toxicity of drugs often limits their therapeutic potential. A number of alternative methods of delivery have been developed, one of which is convection-enhanced delivery (CED), the focus of this review. The authors describe CED as a therapeutic measure and review preclinical studies and the most prominent clinical trials of CED in the treatment of glioblastoma. The utilization of this technique for the delivery of a variety of agents is covered, and its shortcomings and challenges are discussed in detail.

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BACKGROUND: Clival chordomas frequently recur because of their location and invasiveness. OBJECTIVE: To investigate clinical, operative, and anatomic factors associated with clival chordoma recurrence. METHODS: Retrospective review of clival chordomas treated at our center from 1993 to 2013. RESULTS: Fifty patients (56% male) with median age of 59 years (range, 8–76) were newly diagnosed with clival chordoma of mean diameter 3.3 cm (range, 1.5-6.7). Symptoms included headaches (38%), diplopia (36%), and dysphagia (14%). Procedures included transsphenoidal (n = 34), transoral (n = 4), craniotomy (n = 5), and staged approaches (n = 7). Gross total resection (GTR) rate was 52%, with 83% mean volumetric reduction, values that improved over time. While the lower third of the clivus was the least likely superoinferior zone to contain tumor (upper third = 72%/middle third = 82%/lower third = 42%), it most frequently contained residual tumor (upper third = 33%/middle third = 38%/lower third = 63%; P < .05). Symptom improvement rates were 61% (diplopia) and 53% (headache). Postoperative radiation included proton beam (n = 19), cyberknife (n = 7), intensity-modulated radiation therapy (n = 6), external beam (n = 10), and none (n = 4). At last follow-up of 47 patients, 23 (49%) remain disease-free or have stable residual tumor. Lower third of clivus progressed most after GTR (upper/mid/lower third = 32%/41%/75%). In a multivariate Cox proportional hazards model, male gender (hazard ratio [HR] = 1.2/P = .03), subtotal resection (HR = 5.0/P = .02), and the preoperative presence of tumor in the middle third (HR = 1.2/P = .02) and lower third (HR = 1.8/P = .02) of the clivus increased further growth or regrowth, while radiation modality did not. CONCLUSION: Our findings underscore long-standing support for GTR as reducing chordoma recurrence. The lower third of the clivus frequently harbored residual or recurrent tumor, despite staged approaches providing mediolateral (transcranial + endonasal) or superoinferior (endonasal + transoral) breadth. There was no benefit of proton-based over photon-based radiation, contradicting conventional presumptions.

Negative outcomes of mild traumatic brain injury (mTBI) can be exacerbated by repeated insult. Animal models of repeated closed-head mTBI provide the opportunity to define acute pathological mechanisms as the number of mTBI increases. Furthermore, little is known about the effects of mTBI impact site, and how this may affect brain function. We use a closed head, weight drop model of mTBI that allows head movement following impact, in adult female rats to determine the role of the number and location of mTBI on brain pathology and behaviour. Biomechanical assessment of two anatomically well-defined mTBI impact sites were used, anterior (bregma) and posterior (lambda). Location of the impact had no significant effect on impact forces (450 N), and the weight impact locations were on average 5.4 mm from the desired impact site. No between location vertical linear head kinematic differences were observed immediately following impact, however, in the 300 ms post-impact, significantly higher mean vertical head displacement and velocity were observed in the mTBI lambda trials. Breaches of the blood brain barrier were observed with three mTBI over bregma, associated with immunohistochemical indicators of damage. However, an increased incidence of hairline fractures of the skull and macroscopic haemorrhaging made bregma an unsuitable impact location to model repeated mTBI. Repeated mTBI over lambda did not cause skull fractures and were examined more comprehensively, with outcomes following one, two or three mTBI or sham, delivered at 1 day intervals, assessed on days 1-4. We observe a mild behavioural phenotype, with subtle deficits in cognitive function, associated with no identifiable neuroanatomical or inflammatory changes. However, an increase in lipid peroxidation in a subset of cortical neurons following two mTBI indicates increasing oxidative damage with repeated injury in female rats, supported by increased amyloid precursor protein immunoreactivity with three mTBI. This study of acute events following closed head mTBI identifies lipid peroxidation in neurons at the same time as cognitive deficits. Our study adds to existing literature, providing biomechanics data and demonstrating mild cognitive disturbances associated with diffuse injury, predominantly to grey matter, acutely following repeated mTBI.

SUMMARY OBJECTIVE: To examine the prevalence and magnitude of chronic lung disease (CLD) and its association with empiric anti-tuberculosis treatment (due to lack of bacteriologic confirmation) among recurrent tuberculosis (TB) survivors in a human immunodeficiency virus (HIV) prevalent setting. METHODS: Prospective cohort study of retreatment TB survivors in Harare, Zimbabwe. At median follow-up of 2 years post-treatment initiation, we characterized mortality, respiratory impairment, and mental health. RESULTS: Among 175 retreatment TB survivors, 65% of whom were HIV-positive and 21% had been empirically treated, multiparameter CLD was noted at follow-up among 14% of patients (95%CI 9.0–19.7), with a six-fold increase in age-adjusted death in the first year following treatment completion. Empirically treated TB (relative risk [RR] 3.4, 95%CI 1.4–8.3) was associated with CLD, as was the number of previous anti-tuberculosis treatment courses in dose-dependent fashion (three vs. one, RR 6.2, 95%CI 1.7–22.1). Among retreatment TB survivors, 33% (95%CI 26.0–40.1) had persistent respiratory symptoms (Chronic Obstructive Pulmonary Disease Assessment Test score ⩾ 10); 26% (95%CI 19.8–33.0) significant deficits in exercise capacity (median incremental shuttle walk test distance, 550 m; Q1–Q3 440–730 m); 83% (95%CI 75.7–89.7) residual radiographic abnormalities on chest X-ray; 12% (95%CI 6.6–16.1%) moderate-to-severe obstruction on spirometry; and 13% (95%CI 7.6–17.5%) major depression. CONCLUSIONS: Despite successful treatment, retreatment TB survivors retain a substantial risk of morbidity and mortality.