Medical Specialties Commons^™

Developing Novel Therapies For Degenerative Cervical Myelopathy [Ao Spine Recode-Dcm Research Priority Number 7]: Opportunities From Restorative Neurobiology., Aref-Ali Gharooni, Brian K Kwon, Michael G Fehlings, Timothy F Boerger, Ricardo Rodrigues-Pinto, Paul Aarne Koljonen, Shekar N Kurpad, James Harrop, Bizhan Aarabi, Vafa Rahimi-Movaghar, Jefferson R Wilson, Benjamin M Davies, Mark R N Kotter, James D Guest

Department of Neurosurgery Faculty Papers

Study design: Narrative review.

Objectives: To provide an overview of contemporary therapies for the James Lind Alliance priority setting partnership for degenerative cervical myelopathy (DCM) question: 'Can novel therapies, including stem-cell, gene, pharmacological and neuroprotective therapies, be identified to improve the health and wellbeing of people living with DCM and slow down disease progression?'

Methods: A review of the literature was conducted to outline the pathophysiology of DCM and present contemporary therapies that may hold therapeutic value in 3 broad categories of neuroprotection, neuroregeneration, and neuromodulation.

Results: Chronic spinal cord compression leads to ischaemia, neuroinflammation, demyelination, and neuronal loss. Surgical …

James Lind Alliance Priority Setting Partnership For Degenerative Cervical Myelopathy [Ao Spine Recode-Dcm]: An Overview Of The Methodology Used To Process And Short-List Research Uncertainties, Lindsay Tetreault, Oliver Mowforth, Danyal Z Khan, Toto Gronlund, Philip Garwood, Olesja Hazenbiller, James S Harrop, Bizhan Aarabi, Vafa Rahimi-Movaghar, Shekar N Kurpad, James D Guest, Jefferson R Wilson, Brian K Kwon, Michael G Fehlings, Benjamin M Davies, Mark R N Kotter

Department of Neurosurgery Faculty Papers

Study design: Overview of the methods used for a James Lind Alliance (JLA) Priority Setting Partnership (PSP).

Objectives: The objectives of this article are to (i) provide a brief overview of the JLA-facilitated PSP process; (ii) outline how research uncertainties were initially processed in the AO Spine RECODE-DCM PSP; and (iii) delineate the methods for interim prioritization and the priority setting workshop.

Methods: A steering group was created to define the scope for the PSP, organize its activities, and establish protocols for decision-making. A survey was created asking what questions on the diagnosis, treatment, and long-term management of DCM should …

Secondary Syphilis Mimicking Marginal Zone B-Cell Lymphoma, E. Correia, Laura Gleason, Shalini Krishnasamy, Alexa Cohen, Safiyyah Bhatti, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Diagnosing Vitreoretinal Lymphomas—An Analysis Of The Sensitivity Of Existing Tools, Anahita Sehgal, Jose S. Pulido, Arman Mashayekhi, Tatyana Milman, Gabor Gy Deák

Wills Eye Hospital Papers

Vitreoretinal Lymphoma (VRL) is a rare ocular pathology that is notorious for mimicking chronic uveitis, which is a seemingly benign condition in comparison. The most common form of VRL is the diffuse large B-cell type, and there has been a high mortality rate. This dismal prognosis can be improved significantly if the disease is diagnosed early, but until now there is no consensus on an appropriate diagnostic algorithm. We conducted a retrospective search of PubMed Central® and analyzed results from thirty-three studies that were published between 2011–2021. The chosen studies incorporated some popular testing tools for VRL, and our analyses …

Hyperreflective Band On Anterior Segment Optical Coherence Tomography, Zaynab Sajjadi, Zeynep Bas, Carol L Shields

Wills Eye Hospital Papers

No abstract provided.

Establishing Diagnostic Criteria For Degenerative Cervical Myelopathy [Ao Spine Recode-Dcm Research Priority Number 3], Bryn Hilton, Emma L Gardner, Zhilin Jiang, Lindsay Tetreault, Jamie R F Wilson, Carl Moritz Zipser, K Daniel Riew, James D Guest, James Harrop, Michael G Fehlings, Ricardo Rodrigues-Pinto, Vafa Rahimi-Movaghar, Bizhan Aarabi, Paul A Koljonen, Mark R N Kotter, Benjamin M Davies, Brian K Kwon

Department of Neurosurgery Faculty Papers

Study design: Narrative review.

Objectives: To discuss the importance of establishing diagnostic criteria in Degenerative Cervical Myelopathy (DCM), including factors that must be taken into account and challenges that must be overcome in this process.

Methods: Literature review summarising current evidence of establishing diagnostic criteria for DCM.

Results: Degenerative Cervical Myelopathy (DCM) is characterised by a degenerative process of the cervical spine resulting in chronic spinal cord dysfunction and subsequent neurological disability. Diagnostic delays lead to progressive neurological decline with associated reduction in quality of life for patients. Surgical decompression may halt neurologic worsening and, in many cases, improves function. …

Avoidable And Unavoidable Repeat Breast Core Needle Biopsies, Xiaoqin Wang, Fara Shikoh, Mauro Hanaoka, Aurela Clark

Radiology Faculty Publications

Background: Breast core needle biopsies are not perfect and could miss cancer. The need for a repeat breast core biopsy is not uncommon and can occur for a multitude of reasons. Radiologists should carefully correlate the pathology results with imaging features after each breast biopsy and must recognize why certain core biopsies must be repeated to avoid missed or delayed cancer diagnosis. In this review, we discuss the main reasons for repeat core biopsies via case presentation with radiological images and pathological correlation. This review will help multidisciplinary breast care team recognize when to repeat a biopsy to reduce false …

Style Of Meal Service And Feeding Practices Among Mexican American Fathers And Mothers: An Analysis Of Video-Recorded Children’S Evening Mealtime At Home, Carlos Penilla, Jeanne M Tschann, Lauri A Pasch, Elena Flores, Julianna Deardorff, Suzanna M Martinez, Nancy F Butte, Louise C Greenspan

Children’s Nutrition Research Center Staff Publications

The aim of this study was to examine video-recorded observations of evening family mealtime at home among Mexican American children to help elucidate style of meal service, fathers' and mothers' feeding practices and child's eating behavior. Consistent with guidelines for coding behaviors, we analyzed observational data of evening mealtimes of 71 Mexican American children aged eight to 10 years. Regarding style of meal service, in almost all cases (96%), parents plated the child's food, with more available on the table or counter in 40% of the observations. Mothers almost always served the child (94%). Regarding parental feeding practices, parents used …

Longitudinal Changes In Vascular Stiffness And Heart Rate Variability Among Young Adults With Youth-Onset Type 2 Diabetes: Results From The Follow-Up Observational Treatment Options For Type 2 Diabetes In Adolescents And Youth (Today) Study, Amy S Shah, Laure El Ghormli, Samuel S Gidding, Kara S Hughan, Lorraine E Levitt Katz, Dorit Koren, Jeanie B Tryggestad, Fida Bacha, Barbara H Braffett, Silva Arslanian, Elaine M Urbina

Children’s Nutrition Research Center Staff Publications

Aims: (1) To describe changes in arterial stiffness and heart rate variability (HRV) over a 5-year interval, (2) examine changes by sex and race-ethnicity, and (3) evaluate the risk factors associated with the longitudinal changes in arterial stiffness and HRV.

Methods: Participants with youth-onset type 2 diabetes enrolled in the observational follow-up phase of the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial had arterial stiffness [(pulse wave velocity, augmentation index, brachial distensibility] and six indices of HRV measured 5 years apart. Multivariable linear regression models assessed risk factors associated with changes in the outcomes …

Literature Review Of Omicron: A Grim Reality Amidst Covid-19, Suraj Arora, Vishakha Grover, Priyanka Saluja, Youssef Abdullah Algarni, Shahabe Abullais Saquib, Shaik Mohammed Asif, Kavita Batra, Mohammed Y. Alshahrani, Gotam Das, Rajni Jain, Anchal Ohri

School of Medicine Faculty Research

Coronavirus disease 2019 (COVID-19) first emerged in Wuhan city in December 2019, and became a grave global concern due to its highly infectious nature. The Severe Acute Respiratory Coronavirus-2, with its predecessors (i.e., MERS-CoV and SARS-CoV) belong to the family of Coronaviridae. Reportedly, COVID-19 has infected 344,710,576 people around the globe and killed nearly 5,598,511 persons in the short span of two years. On November 24, 2021, B.1.1.529 strain, later named Omicron, was classified as a Variant of Concern (VOC). SARS-CoV-2 has continuously undergone a series of unprecedented mutations and evolved to exhibit varying characteristics. These mutations have largely occurred …

Clinical Characteristics Of Peripheral Neuropathy In Kenyan Patients With Hiv Infection Compared With Patients With Concurrent Hiv Infection And Diabetes Mellitus, Pascal Kuka, Jasmit Shah, Uazman Alam, Reena Shah, Dilraj Sokhi

Internal Medicine, East Africa

Introduction: Persons living with human immunodeficiency virus (HIV) are living longer and at risk of non-communicable diseases, including diabetes mellitus (DM). Both HIV and DM place patients at risk of peripheral neuropathy (PN). Our aim was to demonstrate the prevalence and characteristics of PN in our population of patients with HIV infection compared with concomitant HIV and DM.

Methods: A prospective cross-sectional study was performed at the Aga Khan Hospital in Nairobi, Kenya. Data were collected on demographics and characteristics of DM and HIV. Symptoms and signs of PN were evaluated by Neuropathy Symptom Score, Neuropathy Disability Score, …

Breast Radiation Therapy-Related Treatment Outcomes In Patients With Or Without Germline Mutations On Multigene Panel Testing, Bhavana V Chapman, Diane Liu, Yu Shen, Oluwafikayo O Olamigoke, David S Lakomy, Angelica M Gutierrez Barrera, Shane R Stecklein, Gabriel O Sawakuchi, Scott J Bright, Isabelle Bedrosian, Jennifer K Litton, Benjamin D Smith, Wendy A Woodward, George H Perkins, Karen E Hoffman, Michael C Stauder, Eric A Strom, Banu K Arun, Simona F Shaitelman

Faculty, Staff and Student Publications

PURPOSE: Multigene panel testing has increased the detection of germline mutations in patients with breast cancer. The implications of using radiation therapy (RT) to treat patients with pathogenic variant (PV) mutations are not well understood and have been studied mostly in women with only BRCA1 or BRCA2 PVs. We analyzed oncologic outcomes and toxicity after adjuvant RT in a contemporary, diverse cohort of patients with breast cancer who underwent genetic panel testing.

METHODS AND MATERIALS: We retrospectively reviewed the records of 286 women with clinical stage I-III breast cancer diagnosed from 1995 to 2017 who underwent surgery, breast or chest …

Improving Awareness Could Transform Outcomes In Degenerative Cervical Myelopathy [Ao Spine Recode-Dcm Research Priority Number 1], Benjamin M Davies, Oliver Mowforth, Helen Wood, Zahabiya Karimi, Iwan Sadler, Lindsay Tetreault, Jamie Milligan, Jamie R F Wilson, Sukhvinder Kalsi-Ryan, Julio C Furlan, Yoshiharu Kawaguchi, Manabu Ito, Carl Moritz Zipser, Timothy F Boerger, Alex R. Vaccaro, Rory K J Murphy, Mike Hutton, Ricardo Rodrigues-Pinto, Paul A Koljonen, James Harrop, Bizhan Aarabi, Vafa Rahimi-Movaghar, Shekar N Kurpad, James D Guest, Jefferson R Wilson, Brian K Kwon, Mark R N Kotter, Michael G Fehlings

Department of Orthopaedic Surgery Faculty Papers

Study design: Literature Review (Narrative).

Objective: To introduce the number one research priority for Degenerative Cervical Myelopathy (DCM): Raising Awareness.

Methods: Raising awareness has been recognized by AO Spine RECODE-DCM as the number one research priority. This article reviews the evidence that awareness is low, the potential drivers, and why this must be addressed. Case studies of success from other diseases are also reviewed, drawing potential parallels and opportunities for DCM.

Results: DCM may affect as many as 1 in 50 adults, yet few will receive a diagnosis and those that do will wait many years for it. This leads …

Degenerative Cervical Myelopathy: Development And Natural History [Ao Spine Recode-Dcm Research Priority Number 2]., Aria Nouri, Enrico Tessitore, Granit Molliqaj, Torstein Meling, Karl Schaller, Hiroaki Nakashima, Yasutsugu Yukawa, Josef Bednarik, Allan R Martin, Peter Vajkoczy, Joseph S Cheng, Brian K Kwon, Shekar N Kurpad, Michael G Fehlings, James S Harrop, Bizhan Aarabi, Vafa Rahimi-Movaghar, James D Guest, Benjamin M Davies, Mark R N Kotter, Jefferson R Wilson

Department of Neurosurgery Faculty Papers

Study design: Narrative review.

Objectives: To discuss the current understanding of the natural history of degenerative cervical myelopathy (DCM).

Methods: Literature review summarizing current evidence pertaining to the natural history and risk factors of DCM.

Results: DCM is a common condition in which progressive arthritic disease of the cervical spine leads to spinal cord compression resulting in a constellation of neurological symptoms, in particular upper extremity dysfunction and gait impairment. Anatomical factors including cord-canal mismatch, congenitally fused vertebrae and genetic factors may increase individuals' risk for DCM development. Non-myelopathic spinal cord compression (NMSCC) is a common phenomenon with a prevalence …

Developing Peri-Operative Rehabilitation In Degenerative Cervical Myelopathy [Ao Spine Recode-Dcm Research Priority Number 6]: An Unexplored Opportunity?, Timothy F Boerger, Allison S Hyngstrom, Julio C Furlan, Sukhvinder Kalsi-Ryan, Armin Curt, Brian K Kwon, Shekar N Kurpad, Michael G Fehlings, James Harrop, Bizhan Aarabi, Vafa Rahimi-Movaghar, James D Guest, Jefferson R Wilson, Benjamin M Davies, Mark R N Kotter, Paul A Koljonen

Department of Neurosurgery Faculty Papers

Study design: Narrative review.

Objective: Degenerative cervical myelopathy is one of the most frequent impairments of the spinal cord encountered internationally in adults. Currently, surgical decompression is the recommended treatment for people with DCM (PwCM) presenting with moderate to severe symptoms or neurological deficits. However, despite surgical intervention, not all patients make a complete recovery due to the irreversible tissue damage within the spinal cord. The objective of this review is to describe the state and gaps in the current literature on rehabilitation for PwCM and possible innovative rehabilitation strategies.

Methods: Literature search.

Results: In other neurological disorders such as …

A New Framework For Investigating The Biological Basis Of Degenerative Cervical Myelopathy [Ao Spine Recode-Dcm Research Priority Number 5]: Mechanical Stress, Vulnerability And Time, Benjamin M Davies, Oliver Mowforth, Aref-Ali Gharooni, Lindsay Tetreault, Aria Nouri, Rana S Dhillon, Josef Bednarik, Allan R Martin, Adam Young, Hitoshi Takahashi, Timothy F Boerger, Virginia Fj Newcombe, Carl Moritz Zipser, Patrick Freund, Paul Aarne Koljonen, Ricardo Rodrigues-Pinto, Vafa Rahimi-Movaghar, Jefferson R Wilson, Shekar N Kurpad, Michael G Fehlings, Brian K Kwon, James Harrop, James D Guest, Armin Curt, Mark R N Kotter

Department of Neurosurgery Faculty Papers

Study design: Literature Review (Narrative).

Objective: To propose a new framework, to support the investigation and understanding of the pathobiology of DCM, AO Spine RECODE-DCM research priority number 5.

Methods: Degenerative cervical myelopathy is a common and disabling spinal cord disorder. In this perspective, we review key knowledge gaps between the clinical phenotype and our biological models. We then propose a reappraisal of the key driving forces behind DCM and an individual's susceptibility, including the proposal of a new framework.

Results: Present pathobiological and mechanistic knowledge does not adequately explain the disease phenotype; why only a subset of patients with …

Establishing The Socio-Economic Impact Of Degenerative Cervical Myelopathy Is Fundamental To Improving Outcomes [Ao Spine Recode-Dcm Research Priority Number 8], Benjamin M Davies, Richard Phillips, David Clarke, Julio C Furlan, Andreas K Demetriades, Jamie Milligan, Christopher D Witiw, James Harrop, Bizhan Aarabi, Shekar N Kurpad, James D Guest, Jefferson R Wilson, Brian K Kwon, Alex R. Vaccaro, Michael G Fehlings, Vafa Rahimi-Movaghar, Mark R N Kotter

Department of Orthopaedic Surgery Faculty Papers

Study design: Literature Review (Narrative).

Objective: To contextualize AO Spine RECODE-DCM research priority number 5: What is the socio-economic impact of DCM? (The financial impact of living with DCM to the individual, their supporters, and society as a whole).

Methods: In this review, we introduce the methodology of health-economic investigation, including potential techniques and approaches. We summarize the current health-economic evidence within DCM, so far focused on surgical treatment. We also cover the first national estimate, in partnership with Myelopathy.org from the United Kingdom, of the cost of DCM to society. We then demonstrate the significance of this question to …

Missed Opportunities For Family Planning Counselling Among Postpartum Women In Eleven Counties In Kenya, Mary N. Thiongo, Peter B. Gichangi, Michael Waithaka, Amy Tsui, Linnea A. Zimmerman, Scott Radloff, Marleen Temmerman, Saifuddin Ahmed

Obstetrics and Gynaecology, East Africa

Background: Mothers may access medical facilities for their babies and miss opportunities to access family planning (FP) services. This study was undertaken to describe missed opportunities for FP among women within the extended (0–11months) postpartum period from counties participating in Performance Monitoring and Accountability 2020 (PMA2020) surveys.

Design and setting: This study analysed cross-sectional household survey data from 11 counties in Kenya between 2014 and 2018. PMA2020 uses questions extracted from the Demographic and Health survey (DHS) and DHS defnitions were used. Multivariable logistic regression was used for inferential statistics with p-value of <0.05 considered to be signifcant.

Participants: Women aged 15-49 years …

Partial Treatment Response To Capmatinib In Met-Amplified Metastatic Intrahepatic Cholangiocarcinoma: Case Report & Review Of Literature, Daniel S Lefler, Marni Brisson Tierno, Babar Bashir

Department of Medical Oncology Faculty Papers

Cholangiocarcinoma is a highly morbid gastrointestinal malignancy for which available therapies are limited. Standard of care includes cytotoxic chemotherapies such as gemcitabine, platinum agents, nab-paclitaxel, and fluoropyrimidine analogues. However, tolerability of these regimens varies, and patients who do not tolerate chemotherapy have limited targeted therapies and immunotherapy options. In cholangiocarcinoma, mesenchymal-epithelial transition factor (MET) amplification may present an additional opportunity for a targeted therapeutic approach, especially considering emerging data in non-small cell lung cancer. In this case, we present a metastatic cholangiocarcinoma patient with high-level MET gene amplification for whom capmatinib, a tyrosine kinase inhibitor with activity against c-MET, …

Multicenter Retrospective Review Of Ketamine Use In The Icu., Christine M Groth, Christopher A Droege, Kathryn A Connor, Kimberly Kaukeinen, Nicole M Acquisto, Sai Ho J Chui, Michaelia D Cucci, Deepali Dixit, Alexander H Flannery, Kyle A Gustafson, Nina E Glass, Helen Horng, Mojdeh S Heavner, Justin Kinney, Rachel M Kruer, William J Peppard, Preeyaporn Sarangarm, Andrea Sikora, Velliyur Viswesh, Brian L Erstad, Parkview Health

Parkview Pharmacy Department

This publication is included in our collection because several Parkview pharmacists were involved in the data collection part and acknowledged for the assistance they provided to the overall article. See Comment.

The response of ICU patients to continuously infused ketamine when it is used for analgesia and/or sedation remains poorly established.

OBJECTIVES: To describe continuous infusion (CI) ketamine use in critically ill patients, including indications, dose and duration, adverse effects, patient outcomes, time in goal pain/sedation score range, exposure to analgesics/sedatives, and delirium.

DESIGN SETTING AND PARTICIPANTS: Multicenter, retrospective, observational study from twenty-five diverse institutions in the United States. Patients …

Understanding Deep Learning - Challenges And Prospects, Niha Adnan, Fahad Umer

Department of Surgery Docs

The developments in Artificial Intelligence have been on the rise since its advent. The advancements in this field have been the innovative research area across a wide range of industries, making its incorporation in dentistry inevitable. Artificial Intelligence techniques are making serious progress in the diagnostic and treatment planning aspects of dental clinical practice. This will ultimately help in the elimination of subjectivity and human error that are often part of radiographic interpretations, and will improve the overall efficiency of the process. The various types of Artificial Intelligence algorithms that exist today make the understanding of their application quite complex. …

Role Of Simulation In Open Varicose Veins Surgery: A Systematic Review, Muhammad Ammar Pirzada, Fareed Ahmed Shaikh, Shoaib Badini, Nadeem Ahmed Siddiqui

Department of Surgery Docs

Objective: To assess the types and effectiveness of simulators present for open varicose vein surgery.
Methods: The systematic review was conducted at The Aga Khan University Hospital Karachi and comprised studies published from 1st January 2000 to 30th June 2020 related to open varicose vein surgical procedures done on simulators. Databases searched were PubMed, Medline, Google Scholar, Cochrane and Scopus using appropriate key words. The primary outcome of the review was to assess the effectiveness of different types of simulators used for varicose vein surgery.
Results: Of the 286 articles found, 6(2%) were included. A variety of simulators ranging from …

Otorhinolaryngology Consultations In A Multidisciplinary Hospital - Their Effects On Residents Training On Floor, Ambreen Abdullah Unar, Muhammad Hammad Deewani, Mohammad Sohail Awan, Syeda Amrah Hashmi, Abdul Basit Shah Vardag, Ainulakbar Mughal

Section of Otolaryngology, Head & Neck Surgery

Objective: To determine all types and severity of Otolaryngology consultation requests at our tertiary care center and spectral records of problems related to otorhinolaryngology come across initially by residents which will help in re-shaping residency programmes and enhance patient related care.
Methodology: All otorhinolaryngology consultation received over a three-month period were recorded prospectively. Information collected for each encounter included the time, date, reason for consult at primary service and admission with final ENT diagnosis, any surgical or non-surgical intervention, and basic patient demographics.
Results: A total of 127 consults for inpatients were reviewed from April 2020 to June 2020. Out …

Rates Of Publication Of Fcps Dissertations In International And National Peer-Review Journals Among Residents At Akuh; A Cross Sectional Review Of 15 Years, Ainulakbar Mughal, Syed Akbar Abbas, Abdul Basit Shah Vardag, Muhammad Wasif, Soubia Akhtar, Ayesha Abbasi

Section of Otolaryngology, Head & Neck Surgery

Objective: To see the rate of publication of postgraduate residents' dissertation.
Methods: The single-centre retrospective cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, and comprised research publications from the residents of the departments of Surgery and Medicine who graduated between 2005 and 2020. The surgical subspecialties included Otolaryngology, Ophthalmology, Dentistry, General Surgery, Orthopaedics, Paediatric Surgery, Urology, Plastic Surgery and Cardiovascular Surgery. Data comprised demographics, current institution, current designation, information on dissertation/paper publication, topic of study, year of completion of dissertation, input from the research department, delay in exam due to incomplete dissertation and whether the paper got …

Baseline Blood Count Levels Increase Odds Of Cytopenia Among Cml Patients In Kenya: A Case Control Study, Angela Mcligeyo, Jamilla Rajab, Peter Oyiro, Mohammed Ezzi, Yatich Bett, Matilda Ong’Ondi, Andrew Odhiambo, Sitna Mwanzi, Nicholas Othieno-Abinya

Internal Medicine, East Africa

Background: Imatinib is the gold standard for the treatment of all phases of Philadelphia positive Chronic Myeloid Leukemia (CML). During treatment, patients may develop cytopenia. We aimed to study the baseline characteristics and factors associated with cytopenia at a Nairobi Hospital.

Methods: This was a retrospective case-control study of patients aged ≥18 years on follow-up at the Glivec Inter‑ national Patient Access Program (GIPAP) clinic from 2007 to 2015. The cases consisted of CML patients on imatinib who developed cytopenia. The controls were CML patients on imatinib who did not develop cytopenia. Baseline socio – demographic, clinical, hematologic, …

Chronoradiobiology Of Breast Cancer: The Time Is Now To Link Circadian Rhythm And Radiation Biology, Nicolas Nelson, Joseph Lombardo, Lauren Matlack, Alexandria Smith, Kamryn Hines, Wenyin Shi, Nicole L Simone

Department of Radiation Oncology Faculty Papers

Circadian disruption has been linked to cancer development, progression, and radiation response. Clinical evidence to date shows that circadian genetic variation and time of treatment affect radiation response and toxicity for women with breast cancer. At the molecular level, there is interplay between circadian clock regulators such as PER1, which mediates ATM and p53-mediated cell cycle gating and apoptosis. These molecular alterations may govern aggressive cancer phenotypes, outcomes, and radiation response. Exploiting the various circadian clock mechanisms may enhance the therapeutic index of radiation by decreasing toxicity, increasing disease control, and improving outcomes. We will review the body’s natural circadian …

Anesthetics Affect Peripheral Venous Pressure Waveforms And The Cross-Talk With Arterial Pressure, Ali Z. Al-Alawi, Kaylee R. Henry, Lauren D. Crimmins, Patrick C. Bonasso, Md Abul Hayat, Melvin S. Dassinger, Jeffrey M. Burford, Hanna K. Jensen, Joseph Sanford, Jingxian Wu, Kevin W. Sexton, Morten O. Jensen

Biomedical Engineering Faculty Publications and Presentations

Analysis of peripheral venous pressure (PVP) waveforms is a novel method of monitoring intravascular volume. Two pediatric cohorts were studied to test the effect of anesthetic agents on the PVP waveform and cross-talk between peripheral veins and arteries: (1) dehydration setting in a pyloromyotomy using the infused anesthetic propofol and (2) hemorrhage setting during elective surgery for craniosynostosis with the inhaled anesthetic isoflurane. PVP waveforms were collected from 39 patients that received propofol and 9 that received isoflurane. A multiple analysis of variance test determined if anesthetics influence the PVP waveform. A prediction system was built using k-nearest neighbor (k-NN) …

The Impact Of Age And Sex On Aortic Dissection Outcomes: A True Controversy Or Lack Of Standardization?, Erin F Mccaffrey, Michele Donato, Leeat Keren, Zhenghao Chen, Alea Delmastro, Megan B Fitzpatrick, Sanjana Gupta, Noah F Greenwald, Alex Baranski, William Graf, Rashmi Kumar, Marc Bosse, Christine Camacho Fullaway, Pratista K Ramdial, Erna Forgó, Vladimir Jojic, David Van Valen, Smriti Mehra, Shabaana A Khader, Sean C Bendall, Matt Van De Rijn, Daniel Kalman, Deepak Kaushal, Robert L Hunter, Niaz Banaei, Adrie J C Steyn, Purvesh Khatri, Michael Angelo

Faculty, Staff and Student Publications

Tuberculosis (TB) in humans is characterized by formation of immune-rich granulomas in infected tissues, the architecture and composition of which are thought to affect disease outcome. However, our understanding of the spatial relationships that control human granulomas is limited. Here, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) to image 37 proteins in tissues from patients with active TB. We constructed a comprehensive atlas that maps 19 cell subsets across 8 spatial microenvironments. This atlas shows an IFN-γ-depleted microenvironment enriched for TGF-β, regulatory T cells and IDO1

Construction And Validation Of Prognostic Nomogram For Metaplastic Breast Cancer, Yongfeng Li, Daobao Chen, Haojun Xuan, Mihnea P Dragomir, George A Calin, Xuli Meng, Meng Chen, Hongchuan Jin

Faculty, Staff and Student Publications

In this study we aimed to develop nomogram models for predicting the overall survival (OS) and cancer-specific survival (CSS) of patients with metaplastic breast cancer (MBC). Data of patients diagnosed with MBC from 1973 to 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox analyses were performed to identify independent prognostic factors for OS and CSS of MBC patients. The obtained prognostic variables were combined to construct nomogram models for predicting OS and CSS in patients with MBC. Model performance was evaluated using concordance index (C-index) and calibration plots. Data from 1125 patients …

Combined Il-2, Agonistic Cd3 And 4–1bb Stimulation Preserve Clonotype Hierarchy In Propagated Non-Small Cell Lung Cancer Tumor-Infiltrating Lymphocytes, Parin Shah, Marie-Andrée Forget, Meredith L Frank, Peixin Jiang, Donastas Sakellariou-Thompson, Lorenzo Federico, Roohussaba Khairullah, Chantal Alexia Neutzler, Ignacio Wistuba, Chi-Wan B Chow, Yan Long, Junya Fujimoto, Shiaw-Yih Lin, Anirban Maitra, Marcelo V Negrao, Kyle Gregory Mitchell, Annikka Weissferdt, Ara A Vaporciyan, Tina Cascone, Jack A Roth, Jianjun Zhang, Boris Sepesi, Don L Gibbons, John V Heymach, Cara L Haymaker, Daniel J Mcgrail, Alexandre Reuben, Chantale Bernatchez

Faculty, Staff and Student Publications

Background: Adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) yielded clinical benefit in patients with checkpoint blockade immunotherapy-refractory non-small cell lung cancer (NSCLC) prompting a renewed interest in TIL-ACT. This preclinical study explores the feasibility of producing a NSCLC TIL product with sufficient numbers and enhanced attributes using an improved culture method.

Methods: TIL from resected NSCLC tumors were initially cultured using (1) the traditional method using interleukin (IL)-2 alone in 24-well plates (TIL 1.0) or (2) IL-2 in combination with agonistic antibodies against CD3 and 4-1BB (Urelumab) in a G-Rex flask (TIL 3.0). TIL subsequently underwent a rapid expansion …