Publications by authors named "Julian S Rechberger"

6 Publications

  • Page 1 of 1

Antibody-drug conjugates for H3K27M-mutant diffuse midline gliomas: prospects and challenges.

Ther Deliv 2021 Aug 21;12(8):553-557. Epub 2021 Jul 21.

Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA.

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http://dx.doi.org/10.4155/tde-2021-0045DOI Listing
August 2021

The emerging role of nanotechnology in pursuit of successful drug delivery to H3K27M diffuse midline gliomas.

Nanomedicine (Lond) 2021 07 17;16(16):1343-1346. Epub 2021 May 17.

Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA.

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http://dx.doi.org/10.2217/nnm-2021-0067DOI Listing
July 2021

Convection-enhanced delivery for H3K27M diffuse midline glioma: how can we efficaciously modulate the blood-brain barrier?

Ther Deliv 2021 06 5;12(6):419-422. Epub 2021 May 5.

Department of Neurologic Surgery, Mayo Clinic, Rochester, MN 55905, USA.

Graphical abstract [Formula: see text].
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http://dx.doi.org/10.4155/tde-2021-0026DOI Listing
June 2021

Evaluating infusate parameters for direct drug delivery to the brainstem: a comparative study of convection-enhanced delivery versus osmotic pump delivery.

Neurosurg Focus 2020 01;48(1):E2

1Department of Neurologic Surgery, Mayo Clinic.

Objective: Convection-enhanced delivery (CED) and osmotic pump delivery both have been promoted as promising techniques to deliver drugs to pediatric diffuse intrinsic pontine gliomas (DIPGs). Correspondingly, the aim of this study was to understand how infusate molecular weight (MW), duration of delivery, and mechanism of delivery (CED or osmotic pump) affect volume of distribution (Vd) in the brainstem, to better inform drug selection and delivery in future DIPG investigations.

Methods: A series of in vivo experiments were conducted using rat models. CED and osmotic pump delivery systems were surgically implanted in the brainstem, and different MW fluorescent dextran beads were infused either once (acute) or daily for 5 days (chronic) in a volume infused (Vi). Brainstems were harvested after the last infusion, and Vd was quantified using serial sectioning and fluorescence imaging.

Results: Fluorescence imaging showed infusate uptake within the brainstem for both systems without complication. A significant inverse relationship was observed between infusate MW and Vd in all settings, which was distinctly exponential in nature in the setting of acute delivery across the 570-Da to 150-kDa range. Chronic duration and CED technique resulted in significantly greater Vd compared to acute duration or osmotic pump delivery, respectively. When accounting for Vi, acute infusion yielded significantly greater Vd/Vi than chronic infusion. The distribution in CED versus osmotic pump delivery was significantly affected by infusate MW at higher weights.

Conclusions: Here the authors demonstrate that infusate MW, duration of infusion, and infusion mechanism all impact the Vd of an infused agent and should be considered when selecting drugs and infusion parameters for novel investigations to treat DIPGs.
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http://dx.doi.org/10.3171/2019.10.FOCUS19703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371267PMC
January 2020

Clinical trials for diffuse intrinsic pontine glioma: the current state of affairs.

Childs Nerv Syst 2020 01 6;36(1):39-46. Epub 2019 Sep 6.

Department of Neurologic Surgery, Mayo Clinic, 200 First St. SW, Rochester, MN, 55905, USA.

Purpose: Diffuse intrinsic pontine glioma (DIPG) is a lethal high-grade pediatric brainstem tumor without a cure. Despite numerous clinical trials over the last decades, the prognosis has remained poor. The aim of this update was to report on the status and outcomes of all clinical trials for DIPG performed to better understand the landscape of research efforts for this diagnosis to date.

Methods: The ClinicalTrials.gov database was reviewed in May 2019 for all possible interventional clinical trials that included DIPG as a diagnosis of primary investigation. These were then screened against selection criteria to identify pertinent clinical trials.

Results: Ninety-five clinical trials satisfied all inclusion criteria, with 55 (58%) trials specific to the DIPG diagnosis only. In terms of the most prevalent design features, 42 (44%) were phase I trials, with median expected start and completion years in 2011 (range, 1994-2020) and 2018 (range, 2005-2047), respectively. Median target number of patients to enroll was 38 (range, 1-1500), and the most common primary outcome was safety and toxicity (56%). There were 69 (73%) trials originating from the USA, with 49 (52%) of them being single institutional. Only 10 (11%) trials have reported results to date.

Conclusions: To date, 95 clinical trials investigating DIPG with specific emphasis have been registered on ClinicalTrials.gov. There were only a small number of trials that had study results available, and they uniformly reported non-significant improvement to prognosis. Given the rarity and lethality of DIPG, which limits the accumulation of large cohorts, our results mandate the need for more robust, systematic clinical trial design to minimize redundancies and maximize yield in the future.
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http://dx.doi.org/10.1007/s00381-019-04363-1DOI Listing
January 2020

The 100 Most-Cited Articles About Convection-Enhanced Delivery to the Brain: A Bibliometric Analysis.

World Neurosurg 2019 Sep 29;129:497-502.e6. Epub 2019 May 29.

Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota, USA. Electronic address:

Background: Convection-enhanced delivery (CED) overcomes the blood-brain barrier to deliver therapy within the central nervous system. Our aim was to evaluate citation and other bibliometric characteristics of the 100 most-cited articles about CED to the brain to better understand the state of research efforts in the field.

Methods: Elsevier's Scopus database was searched for the 100 most-cited articles that focused on CED to the brain. Articles were dichotomized as either primarily basic science (BSc) or clinical (CL) articles. Various bibliometric parameters were summarized, and BSc and CL articles were compared.

Results: Of the 100 most-cited articles, 64 (64%) were BSc and 36 (36%) were CL. The most common indications reported were brain tumors (59%) and Parkinson disease (5%). Overall median values were as follows: citation count, 102 (range, 70-933); citation rate per year, 9.0 (range, 3.7-49.4); number of authors, 5 (range, 1-25); and publication year, 2006 (range, 1994-2015). Articles were published in a total of 48 different journals, and predominately originated in the United States (n = 78, 78%). BSc and CL articles were statistically comparable in terms of bibliometric parameters.

Conclusions: In the 100 most-cited articles about CED to the brain, there were more BSc articles compared with CL articles; however, they were comparable with respect to the reported bibliometric parameters. Given that the peak year of publication of these articles was more than a decade ago, we anticipate that the field will shift toward more CL articles once effective therapies to be delivered via CED are discovered.
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http://dx.doi.org/10.1016/j.wneu.2019.05.179DOI Listing
September 2019
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