Bypassing the Blood-Brain Barrier to Treat Brain Cancer: A Systematic Review of the Efficacy of Carmustine Wafer Implant Therapy

Here is the abstract of our newest accepted publication, Please follow the link below!

https://msrj.chm.msu.edu/wp-content/uploads/2022/10/198-ePub.pdf

Authors:

Mark Sharobim BSc, MSc1*, Peter A. Tsivis, MD, MBA1,2

1Saba University School of Medicine, The Bottom, Saba, The Caribbean Netherlands
2Rocky Vista University College of Osteopathic Medicine, Ivins, Utah, USA

Introduction:
Gliomas are neoplasms of the central nervous system (CNS). Despite aggressive treatment, median survival of malignant tumors remains poor at 12 – 18 months. Newer treatments allow delivery of therapeutic substances across the selectively permeable blood-brain barrier (BBB). This allows for chemotherapeutics to more easily reach their target location in the CNS. Drug eluting wafers made up of carmustine can be placed in the surgical resection cavity of a tumor and clinical trials to date have demonstrated their utility.

Hypothesis:
Bypassing the BBB to allow greater accumulation of chemotherapeutics in the CNS will improve clinical outcomes in glioma patients.

Methods:
Studies from medical literature databases describing trials using carmustine wafers implanted after glioma resection were obtained. To test our hypothesis, the available data using this therapy was compared to current first line treatment data for glioma as described by Stupp and colleagues. The inclusion criterion for efficacy analysis was histopathologically confirmed primary glioma. Exclusion criteria included presence of metastasis or pediatric tumors.

Results:
10 studies describing wafer therapy use were initially gathered, encompassing over 500 patients. 6 studies met criteria for treatment efficacy analysis. 4 of 6 (75%) trials exhibited significant survival advantage as compared to control treatment. Furthermore, 3 of the 4 (75%) studies showing significance also demonstrated equal or higher percent increase in overall survival from control as compared to data generated from current first line therapy.

Conclusion:
Treatments bypassing the BBB are not currently standard-of-care for patients with glioma. We uncovered that most trials using carmustine implants post tumor resection describe increased overall survival, however in specific cohorts. Diverting the BBB in general may also have fewer side effects in contrast to classical routes of therapy. Future work is needed to develop similar therapeutics that improve outcomes in all age, gender, and prognostic risk factor populations.

Key words: Glioblastoma, Glioblastoma Multiforme, Blood-Brain Barrier, Drug Delivery Systems, Carmustine, Carmustine Wafers, Blood-Brain Barrier Disruption.

A Narrative Review of the Current Evidence of Fecal Microbiota Transplant as Curative Therapy for Recurrent Clostridioides difficile Infection

Interested in the gut microbiome?  Read the abstract and click the link below for our newest accepted publication!

http://msrj.chm.msu.edu/wp-content/uploads/2022/10/218-ePub.pdf

Authors: Divya Lakshmi Yerramsetty, Dipendra R. Pandeya, Ph.D.
Medical University of the Americas, Devens, MA, USA

Hypothesis: Compared to the flawed antimicrobial interventions, fecal microbiota transplantation (FMT) is more efficacious and safer in offering a significant clinical resolution of recurrent Clostridioides difficile (rCDI) – the world’s leading hospital-acquired infection.

Methods: An electronic search using Medscape, PubMed, and Google Scholar databases, limited only to articles published in academic journals with full-text access within the past ten years (2010-2020). Selection criteria consisted of quality research studies with relevant findings from patient follow-up post-FMT, considering both primary and secondary endpoints of the investigations. An evidence table was created to organize and evaluate the notable features of each source.

Results: Three RCTs, two retrospective cohort studies, and two systematic reviews and meta-analyses have established that FMT is an effective alternative to standard care in treating rCDI. Multiple infusions of FMT as a monotherapy and rescue treatment demonstrated near-complete clinical resolution in patients with rCDI. Further management of rCDI with the recommended first-line agents (e.g., vancomycin and fidaxomicin) proved counterproductive to FMT in comparative studies.

Conclusions: With its unappealing aesthetics and under-researched long-term implications, there is increased reluctance to FMT’s regular use. Before declaring the novel procedure as the best form of medical practice, future studies should have a stronger emphasis on vancomycin and fidaxomicin to allow for the effective comparison of FMT to non-FMT treatments. Despite the existing limitations, including insufficient sample sizes, FMT has still shown overwhelming promise as a curative treatment for rCDI.

Keywords: Dysbiosis, gut microbiome, FMT, human feces, rCDI, treatment

Establishing the Hormonal Relationship between Polycystic Ovary Syndrome and Hypothyroidism: A Literature Review

Here is the abstract of our newest accepted publication, Please follow the link below!

http://msrj.chm.msu.edu/wp-content/uploads/2020/08/MSRJ2019187.pdf

Deborah Anuoluwapo Aina, Saba University School of Medicine, Devens, MA, USA, Dutch Caribbean

Objective: The aim of this literature review is to evaluate the hormonal relationship between polycystic ovary syndrome and hypothyroidism.

Methods: Electronic databases such as Ebscohost and PubMed were searched, using words and phrases specific to the topic. Journal articles were filtered for publications from no earlier than 2008 to ensure accuracy and relevance.

Results: Anti-thyroid peroxidase antibodies and thyroid-stimulating hormone were significantly higher in polycystic ovary syndrome patients compared to controls (P<0.05). Polycystic ovary syndrome patients also had a statistically significant higher prevalence of autoimmune thyroiditis (P=0.035) and subclinical hypothyroidism (P=0.0133) compared to controls. In polycystic ovarian syndrome patients with thyroid-stimulating hormone levels ≥2.5 mIU/L, a significantly increased insulin resistance (P=0.007) and a significantly decreased insulin sensitivity (P=0.003) were observed compared to same patients with thyroid-stimulating hormone levels <2.5 mIU/L. Serum triglycerides were significantly higher in polycystic ovary syndrome patients with subclinical hypothyroidism compared to same patients with normal thyroid function (P=0.013). A significant positive correlation was present between luteinizing hormone and thyroid volume (P=0.007) and between anti-thyroid peroxidase antibodies and thyroid volume (P<0.0001). With thyroid hormone replacement, there was a significant increase in insulin sensitivity and free T3 /T4 levels, with a corresponding decrease in serum thyroid-stimulating hormone, prolactin, estradiol, insulin resistance, and free testosterone in polycystic ovary syndrome patients with untreated hypothyroidism. The polycystic-appearing ovaries and ovarian volumes in these patients also significantly regressed (P<0.05).

Conclusion: Polycystic ovary syndrome is associated with hypothyroidism. Hence, achieving euthyroidism may improve the clinical and morphologic characteristics of polycystic ovary syndrome.

Keywords: PCOS, hypothyroidism, levothyroxine, polycystic ovary, hormone, thyroid, autoimmune, insulin resistance

Ultrasound vs CT for Diagnosing Acute Appendicitis and Appendicitis Treatment Altering Conditions

Interested in imaging modalities and their effectiveness in diagnostics?  Read the abstract and click the link below for our newest accepted publication!

 

Ultrasound vs CT for Diagnosing Acute Appendicitis and Appendicitis Treatment Altering Conditions

Christopher Borowy, MS-IV1*, Luke Rond, D.O2, John Ashurst, D.O2, and Stefan Merrill, M.D2
1Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
2Department of Emergency Medicine, Kingman Regional Medical Center, Kingman, AZ, USA

Introduction: Acute appendicitis is the most common cause of atraumatic abdominal pain in children over 1 year of age. Even though diagnostic imaging modalities have evolved over the past 20 years, accurate diagnosis of acute appendicitis still presents as a challenge. Computed tomography (CT) is currently the most commonly used radiographic test for acute appendicitis. Unlike CT, ultrasound (US) does not require ionizing radiation which is harmful to the patient. Even though the specificity of US has been well studied in acute appendicitis, CT is still commonly requested after a positive US. Till date, there has been no published research evaluating the utility of US in changing management in appendicitis.

Purpose: The purpose of the study is to compare the ability of US and CT to diagnose pathology proven acute appendicitis and to predict Appendicitis Treatment Altering Conditions (ATAC).

Methods: This is a retrospective cohort study that compares the positive predictive value (PPV) and the ATAC rate of US and CT when diagnosing acute appendicitis.

Results: There were 432 appendicitis cases reported between 1 October 2012 and 30 June 2017. Of those cases, 409 were diagnosed by CT and 23 were diagnosed by US. The PPV of both modalities was above 90% (CT = 97%, US = 95%), and the ATAC rates were statistically similar (CT = 14%, US = 22%, P = 0.21).

Conclusion: The study supports that a positive US for appendicitis is as diagnostic as a positive CT. Therefore, adding on a CT scan after a positive US does not help recognize other sources of intra-abdominal pathology that would negate doing a laparoscopy.

Keywords: US, ultrasound, CT, CAT, ATAC, appendicitis, sensitivity, positive predictive value, PPV

 

Transfemoral Aortic Valve-in-Valve Replacement in Patient with Aortic Root Pseudoaneurysm

Another new and interesting article from our Fall 2019 Issue!  Read the abstract below and click on the link for the full article.

Transfemoral Aortic Valve-in-Valve Replacement in Patient with Aortic Root Pseudoaneurysm (Click link for full PDF)

 

Authors: Mark A. Nolan, P.E., M.Eng1, Stephane Leung Wai Sang, M.D., MSc2

Background: Transcatheter aortic valve replacement (TAVR) was successfully performed to treat aortic regurgitation (AR) in a patient with a failed aortic valve replacement complicated by aortic root pseudoaneurysm.

Case Presentation: A 92-year-old male presented with acute decompensated congestive heart failure secondary to AR of a previously implanted stentless aortic bioprosthesis, complicated by a 2.5 x 1.7 cm pseudoaneurysm of the aortic root.

Conclusions: Complex aortic root and valve disease can be safely and effectively addressed through the use of TAVR in high-risk patients. The presence of a pseudoaneurysm should not preclude successful TAVR.

 

Association between Total Knee Arthroplasty and Subtalar Joint Changes: A Cadaver Study

New article from the MSRJ 2019 Fall issue is now up on the site! Read the abstract or click on the link below for the full article.

Association between Total Knee Arthroplasty and Subtalar Joint Changes: A Cadaver Study (Click link for full PDF article)

Authors: Dominick J. Casciato, B.A.1*, Natalie A. Builes, B.A.2, Luis A. Rodriguez Anaya, DPM1, Bibi N. Singh, DPM1

Background: Total knee arthroplasty (TKA) has become the procedure of choice for those suffering from debilitating degenerative joint disease of the knee; however, new research suggests that functional changes in the rearfoot occur following the procedure to compensate for gait changes. This pilot study investigates subtalar joint (STJ) changes in cadavers with TKAs.

Methods: Four embalmed cadavers with a unilateral TKA were disarticulated at the STJ and the calcaneal articular facets were imaged. The length, width, and area of these facets ipsilateral to the joint replacement were measured using image analysis software and compared to the contralateral side.
Results: All cadavers exhibited evidence of anatomical changes at the STJ. Moreover, a transition to an anatomically unstable STJ was observed.

Conclusions: This study suggests that biomechanical compensation at the STJ may result in anatomical changes in the joint in which form of the joint follows function. Though this pathology may have developed prior to such arthroplasty, the unilateral nature of the facet changes emphasizes the need to further investigate and address gait abnormalities before and after joint replacement to optimize biomechanics in the arthritic knee.

 

 

 

Volume 7: Spring 2019 Issue

MSRJ Vol. 7 Spring 2019

The Spring 2019 issue is hot off the press! Click on the cover art to view and share the full issue!

Thank you to our artist, authors, student and faculty reviewers, and our E-Board for all your hard work and dedication to advancing evidence-based medicine!

Interested in a print copy? email us at @: contact@msrj.org

MSRJ 2019 Cover Art Competition

The Medical Student Research Journal is hosting its first cover art competition! This is a competition to have your art featured in the Fall 2019 edition of the Medical Student Research Journal. This is a great opportunity to showcase humanism in medicine and earn a CITATION that you can add to your curriculum vitae!

Details:

• Competition Dates?  June 1 to August 31, 2019
• Theme?  Medicine
• Who is eligible?  All MSU graduate and undergraduate students, KCAD students.
• How to compete? Please submit artwork in PDF or JPEG format by 11:59pm, August 31 2019.

Please send submissions to:
jacob.purcell@msrj.chm.msu.edu

Check out the official flyer and last years cover art below:

Fall 2018 publication cover

Equator Manuscript Reporting Guidelines

Hello authors,

We at MSRJ are working hard to streamline the manuscript review process to reduce the time between submission date and when a decision is made on final publication.   One of the numerous barriers to fast and efficient manuscript review is something that is under author control – the quality of the submitted manuscript.   In this post, I will describe an indispensable tool all authors should use in preparing a manuscript for publication.

The resource I am referring to is the “Reporting Guideline”.  A reporting guideline is a document that outlines the minimum required content for your manuscript.  It is like a checklist of what information should be included in your manuscript. The purpose of a guideline is to ensure authors provide required information such that a reader knows exactly what you did in your study, and if so desired, they could repeat your study using only your manuscript as a guide. The goal is to ensure all published research papers have proper reporting of details to ensure they can be critically appraised, utilized in systematic reviews, or repeated.

Use of a reporting guideline when writing your manuscript will also help shorten the time it takes from manuscript submission to journal decision.  One of the major delays in the review process occurs when submitted manuscripts have missing information.   This requires the journal to request a resubmission of the manuscript with the missing information, often requiring a second review.  To avoid such a needless delay, we strongly recommend using a reporting guideline when submitting a manuscript to MSRJ.

equator_logo

So what should MSRJ authors do?

(1) Go to The Equator Network website (http://www.equator-network.org/). The Equator Network hosts hundreds of reporting guidelines on many different study design types.  There are reporting guidelines for randomized trials, observational studies, systematic reviews, qualitative research, and case reports, among many others.

(2) On the Equator Network website, find the guideline appropriate to your study type.

(3) Once you have found the appropriate guideline, use the associated checklists to ensure you report all required information.

(4) Finally, cite the guideline you used in your manuscript.

By utilizing the appropriate guideline and adhering to its recommendations, you will ensure a smooth initial review and help improve the quality of research reporting in general.

Sincerely,

Mark Trottier, Ph.D.

MSRJ Faculty Advisor