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Full-Text Articles in Medicine and Health Sciences

Small Extracellular Vesicle-Mediated Itgb6 Sirna Delivery Downregulates The Αvβ6 Integrin And Inhibits Adhesion And Migration Of Recipient Prostate Cancer Cells, Shiv Ram Krishn, Vaughn Garcia, Nicole M Naranjo, Fabio Quaglia, Christopher D Shields, Maisha A Harris, Andrew V Kossenkov, Qin Liu, Eva Corey, Dario C Altieri, Lucia R Languino Dec 2022

Small Extracellular Vesicle-Mediated Itgb6 Sirna Delivery Downregulates The Αvβ6 Integrin And Inhibits Adhesion And Migration Of Recipient Prostate Cancer Cells, Shiv Ram Krishn, Vaughn Garcia, Nicole M Naranjo, Fabio Quaglia, Christopher D Shields, Maisha A Harris, Andrew V Kossenkov, Qin Liu, Eva Corey, Dario C Altieri, Lucia R Languino

Department of Cancer Biology Faculty Papers

The αVβ6 integrin, an epithelial-specific cell surface receptor absent in normal prostate and expressed during prostate cancer (PrCa) progression, is a therapeutic target in many cancers. Here, we report that transcript levels of ITGB6 (encoding the β6 integrin subunit) are significantly increased in metastatic castrate-resistant androgen receptor-negative prostate tumors compared to androgen receptor-positive prostate tumors. In addition, the αVβ6 integrin protein levels are significantly elevated in androgen receptor-negative PrCa patient derived xenografts (PDXs) compared to androgen receptor-positive PDXs. In vitro, the androgen receptor-negative PrCa cells express high levels of the αVβ6 integrin compared to androgen receptor-positive PrCa cells. Additionally, expression ...


Gibbon Surgical Review, Volume 5, Issue 1, 2022 Jun 2022

Gibbon Surgical Review, Volume 5, Issue 1, 2022

Gibbon Surgical Review

In this Issue:

A History of ECMO and its Use During the COVID-19 Pandemic, 6

The First Pig-to-Human Heart Xenotransplantation, 8

Residency Interviewing in the Zoom Era, 9

An Interview with Dr. Andrew Newman, 10

Lung Transplantation for Patients with Severe COVID-19 Pulmonary Disease, 12

Risk Factors for Five-year Mortality after Carotid Endarterectomy, 14

An Interview with Dr. Scott Cowan,16

General Surgery 101: The J-Pouch, 18

The Business of Surgery: Recognizing Barriers to Gender Equity, 20


Gibbon Surgical Review, Volume 4, Issue 1, 2021 Jun 2022

Gibbon Surgical Review, Volume 4, Issue 1, 2021

Gibbon Surgical Review

Contents:

The Evolution of Surgical Practice During the Ongoing COVID-19 Pandemic, 4

Socially responsible surgical care: a movement committed to surgical equity, 6

The MS4 Perspective on the Path to Surgery, 8

The Role of Empathy in Surgery: A Commentary and Conversation with Dr. Harish Lavu, 10

Interview with Dr. Olugbenga Okusanya, 12

The Ultimate Test in Medicine: Adapting Patient Care, Procedures, and Training During a Pandemic, 14

Robotic Surgery: Development, Applications, and Future Directions,16

Editorial Board and Reviewers, 19

Gibbon Surgical Society, 20

John H. Gibbon Jr., MD, 21

Also in this Issue:

The Jefferson Legacy: Where are ...


Catchem Before They Fall Through The Cracks: Implementation Of A Comprehensive Atherosclerosis Treatment Collaborative Health System Transition Of Care Multidisciplinary Clinic, Youssef Bessada, Taki Galanis, Brandi Thoma, Luis Eraso, Walter Kraft, Geno Merli, Dina Orapallo, Lynda Thomson, Heather Yenser Jun 2022

Catchem Before They Fall Through The Cracks: Implementation Of A Comprehensive Atherosclerosis Treatment Collaborative Health System Transition Of Care Multidisciplinary Clinic, Youssef Bessada, Taki Galanis, Brandi Thoma, Luis Eraso, Walter Kraft, Geno Merli, Dina Orapallo, Lynda Thomson, Heather Yenser

Pharmacy Presentations, Posters, and Grand Rounds

Introduction: Peripheral Artery Disease (PAD) is a common atherosclerotic cardiovascular (CV) disease that increases the risk for fatal and non-fatal CV events. Guidelines for the treatment of PAD recommend that in addition to necessary revascularization, general CV prevention with optimal medical therapy is of utmost importance and management is recommended to be multidisciplinary. While the prevalence of PAD in various practices is high, physician awareness of the PAD diagnosis is relatively low and the pharmacological component of preventative CV care is often underutilized resulting in patients receiving less intensive treatment. With new pharmacological agents, including advances in antithrombotic therapy, contributing ...


Coil Embolization Of Ruptured Distal Renal Artery Pseudoaneurysm With Gross Hematuria And Hemorrhagic Shock, Andrea Mcsweeney, Anand Tarpara, Dawn Salvatore, Paul J Dimuzio, Michael Nooromid, Babak Abai Jun 2022

Coil Embolization Of Ruptured Distal Renal Artery Pseudoaneurysm With Gross Hematuria And Hemorrhagic Shock, Andrea Mcsweeney, Anand Tarpara, Dawn Salvatore, Paul J Dimuzio, Michael Nooromid, Babak Abai

Department of Surgery Faculty Papers

Renal artery pseudoaneurysms have been infrequently reported in the literature. In the present report, we have described a case of a ruptured renal artery pseudoaneurysm requiring coil embolization. A 49-year-old man had presented to our institution with a hypertensive emergency. Computed tomography revealed a 3.4-cm right renal artery pseudoaneurysm. Nonemergent coil embolization was planned for the following day. However, he became hypotensive, exsanguinating frank blood from the urethra. An arteriogram showed extravasation of contrast into the pseudoaneurysm sac, renal pelvis, and ureter, consistent with intrarenal pseudoaneurysm rupture. We have demonstrated coil embolization as a method of repairing a ruptured ...


Retained Lens Fragment Presenting 32 Years After Cataract Extraction, Thomas Tien, Marcos A Crespo, Tatyana Milman, Zeba Syed Jun 2022

Retained Lens Fragment Presenting 32 Years After Cataract Extraction, Thomas Tien, Marcos A Crespo, Tatyana Milman, Zeba Syed

Wills Eye Hospital Papers

Purpose: To report a patient with retained lens material presenting over three decades after initial cataract extraction with fluctuating corneal edema and intraocular inflammation.

Observations: A 66-year-old man presented with a first episode of decreased vision and photophobia 32 years after cataract extraction without intraocular lens implantation in the right eye. Slit lamp examination revealed a tan-colored oblong mass in the inferior angle, in addition to corneal edema and an anterior chamber reaction. The patient was aphakic with traumatic mydriasis, and accordingly it was noted that the mass shifted location between anterior and posterior chambers over subsequent evaluations. The anterior ...


Variation In Molecularly Defined Prostate Tumor Subtypes By Self-Identified Race, Kevin H. Kensler, H. Lee Moffitt Cancer Center And Research Institute, Mohamed Alshalalfa, Bruce J. Trock, Stephen J. Freedland, Michael R. Freeman, Sungyong You, Brandon A. Mahal, Robert Den, Adam Dicker, R. Jeffrey Karnes, Eric A. Klein, Priti Lal, Yang Liu, Elai Davicioni, Walter Rayford, Kosj Yamoah, Timothy R. Rebbeck Jun 2022

Variation In Molecularly Defined Prostate Tumor Subtypes By Self-Identified Race, Kevin H. Kensler, H. Lee Moffitt Cancer Center And Research Institute, Mohamed Alshalalfa, Bruce J. Trock, Stephen J. Freedland, Michael R. Freeman, Sungyong You, Brandon A. Mahal, Robert Den, Adam Dicker, R. Jeffrey Karnes, Eric A. Klein, Priti Lal, Yang Liu, Elai Davicioni, Walter Rayford, Kosj Yamoah, Timothy R. Rebbeck

Department of Radiation Oncology Faculty Papers

Background: Socioeconomic and health care utilization factors are major drivers of prostate cancer (PC) mortality disparities in the USA; however, tumor molecular heterogeneity may also contribute to the higher mortality among Black men. Objective: To compare differences in PC subtype frequency and genomic aggressiveness by self-identified race. Design, setting, and participants: Five molecular subtype classifiers were applied for 426 Black and 762 White PC patients in the Decipher Genomics Resource Information Database (GRID). Outcome measurements and statistical analysis: Differences in subtype frequency and tumor genomic risk (Decipher score >0.6) by race were evaluated using χ2 tests and multivariable-adjusted logistic ...


Efficacy Of Cenobamate For Uncontrolled Focal Seizures In Patients With Previous Epilepsy-Related Surgery: Post Hoc Analysis Of A Phase 3, Multicenter, Open-Label Study, Bassel Abou-Khalil, Sami Aboumatar, Pavel Klein, Gregory L Krauss, Michael R Sperling, William E Rosenfeld May 2022

Efficacy Of Cenobamate For Uncontrolled Focal Seizures In Patients With Previous Epilepsy-Related Surgery: Post Hoc Analysis Of A Phase 3, Multicenter, Open-Label Study, Bassel Abou-Khalil, Sami Aboumatar, Pavel Klein, Gregory L Krauss, Michael R Sperling, William E Rosenfeld

Department of Neurology Faculty Papers

Objective: This post hoc analysis of 10 US study sites from a long-term open-label phase 3 study of adjunctive cenobamate evaluated the efficacy of cenobamate in patients with prior epilepsy-related surgery.

Methods: Patients with uncontrolled focal seizures despite taking stable doses of 1-3 concomitant antiseizure medications (ASMs) received increasing doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) at 2-week intervals over 12 weeks (target dose, 200 mg/day). Further increases up to 400 mg/day using biweekly 50-mg/day increments were allowed during the maintenance phase. Dose adjustments of cenobamate and concomitant ASMs were allowed. Data ...


Insight, Volume 2, Issue 1, 2022 May 2022

Insight, Volume 2, Issue 1, 2022

inSIGHT

10- A New Dimension to Offer (Ari August)

14- Neuro-Ophthalmology Subspecialty Highlight: with Dr. Sarah Thornton, Wills Eye Hospital (Joseph D. DeSimone)

19- A Day in the Life in the Wills Eye ER (Samara Hamou)

22- Origins of the Wills Eye Manual: Surviving the Test of Time (Jordan Safran)

26- GATT: A Micro-invasive Glaucoma Surgeryand a Big Step for Glaucoma Treatment (Moses Im)

31- Manual Small-Incision Cataract Surgery (Ankur Nahar)

34- A Look into Oculoplastics: RepairingLower Eyelids Defects From Carcinomas (Cameron Haghshenas)

38- Seeing Eye to Eye: An Overview of Strabismus and Approach to Treatment (Shreya Swaminathan)


Patient-Reported Outcome Measures-Challenges And Opportunities For China., Donald E Casey May 2022

Patient-Reported Outcome Measures-Challenges And Opportunities For China., Donald E Casey

College of Population Health Faculty Papers

No abstract provided.


The Use Of Computerized Tomography Scans In Elective Knee And Hip Arthroplasty-What Do They Tell Us And At What Risk?, Taylor D'Amore, Gregg R Klein, Jess H. Lonner May 2022

The Use Of Computerized Tomography Scans In Elective Knee And Hip Arthroplasty-What Do They Tell Us And At What Risk?, Taylor D'Amore, Gregg R Klein, Jess H. Lonner

Rothman Institute Faculty Papers

The average background radiation exposure in the United States has nearly doubled over the previous quarter century, with almost all the increase derived from medical imaging. Nearly 2% of all cancers in the United States may be attributable to radiation from computerized tomography (CT) scans. Given the nondiagnostic nature of CT scans that are used in elective knee and hip arthroplasty today, special consideration should be given to the inherent risk of radiation exposure with routine use of this technology. Methods to decrease radiation exposure including modulating the settings of the CT machine and using alternative non-CT-based systems can decrease ...


A State-Wide Education Program On Opioid Use Disorder: Influential Community Members' Knowledge, Beliefs, And Opportunities For Coalition Development, Lindsey Hohmann, Haley Phillippe, Karen Marlowe, Ruth Jeminiwa, Natalie Hohmann, Salisa Westrick, Amanda Fowler, Brent Fox May 2022

A State-Wide Education Program On Opioid Use Disorder: Influential Community Members' Knowledge, Beliefs, And Opportunities For Coalition Development, Lindsey Hohmann, Haley Phillippe, Karen Marlowe, Ruth Jeminiwa, Natalie Hohmann, Salisa Westrick, Amanda Fowler, Brent Fox

College of Pharmacy Faculty Papers

Background: Deep South states, particularly Alabama, experience disproportionately higher opioid prescribing rates versus national rates. Considering limited opioid use disorder (OUD) providers in this region, collaborative efforts between non-healthcare professionals is critical in mitigating overdose mortality. The Alabama Opioid Training Institute (OTI) was created in 2019 to empower community members to take action in combatting OUD in local regions. The OTI included: 1) eight full-day in-person conferences; and 2) an interactive mobile-enabled website ( https://alabamaoti.org ). This study assessed the impact of the OTI on influential community members' knowledge, abilities, concerns, readiness, and intended actions regarding OUD and opioid overdose ...


Comparison Of Clinical Outcomes Following Osteochondral Allograft Transplantation For Osteochondral Versus Chondral Defects In The Knee, John Reza Matthews, Joseph Brutico, Jeremy Heard, Kashyap Chauhan, Bradford Tucker, Kevin Freedman May 2022

Comparison Of Clinical Outcomes Following Osteochondral Allograft Transplantation For Osteochondral Versus Chondral Defects In The Knee, John Reza Matthews, Joseph Brutico, Jeremy Heard, Kashyap Chauhan, Bradford Tucker, Kevin Freedman

Rothman Institute Faculty Papers

Purpose: Osteochondral allograft (OCA) transplantation is a restorative technique for addressing articular cartilage defects by transferring mature viable chondrocytes with subchondral bone into size-matched lesions. The purpose of this study was to compare differences in clinical and functional outcomes in patients treated with OCA for osteochondral defects compared with isolated chondral pathology.

Methods: A retrospective review identified patients who underwent OCA transplantation and grouped them into osteochondral or isolated chondral pathology. Demographic data, surgical history, lesion characteristics, complications, and rate of subsequent surgery were reviewed. The review included 86 patients (24 osteochondral, 62 chondral) with a mean follow-up of 5 ...


Assessing The Coverage Of Us Cancer Center Primary Catchment Areas., Amy E Leader, Christopher Mcnair, Christina Yurick, Matthew Huesser, Elizabeth Schade, Emily E Stimmel, Caryn Lerman, Karen E Knudsen May 2022

Assessing The Coverage Of Us Cancer Center Primary Catchment Areas., Amy E Leader, Christopher Mcnair, Christina Yurick, Matthew Huesser, Elizabeth Schade, Emily E Stimmel, Caryn Lerman, Karen E Knudsen

Kimmel Cancer Center Faculty Papers

Background: Cancer centers are expected to engage communities and reduce the burden of cancer in their catchment areas. However, the extent to which cancer centers adequately reach the entire US population is unknown. Methods: We surveyed all members of the Association of American Cancer Institutes (N ¼ 102 cancer centers) to document and map each cancer center’s primary catchment area. Catchment area descriptions were aggregated to the county level. Catchment area coverage scores were calculated for each county and choropleths generated representing coverage across the US. Similar analyses were used to overlay US population density, cancer incidence, and cancer-related ...


Bacille Calmette-Guérin Vaccine Reprograms Human Neonatal Lipid Metabolism In Vivo And In Vitro, Joann Diray-Arce, Asimenia Angelidou, Kristoffer Jarlov Jensen, Maria Giulia Conti, Rachel S Kelly, Matthew Pettengill, Mark Liu, Simon D Van Haren, Scott D Mcculloch, Greg Michelloti, Olubukola Idoko, Tobias R Kollmann, Beate Kampmann, Hanno Steen, Al Ozonoff, Jessica Lasky-Su, Christine S Benn, Ofer Levy May 2022

Bacille Calmette-Guérin Vaccine Reprograms Human Neonatal Lipid Metabolism In Vivo And In Vitro, Joann Diray-Arce, Asimenia Angelidou, Kristoffer Jarlov Jensen, Maria Giulia Conti, Rachel S Kelly, Matthew Pettengill, Mark Liu, Simon D Van Haren, Scott D Mcculloch, Greg Michelloti, Olubukola Idoko, Tobias R Kollmann, Beate Kampmann, Hanno Steen, Al Ozonoff, Jessica Lasky-Su, Christine S Benn, Ofer Levy

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Vaccines have generally been developed with limited insight into their molecular impact. While systems vaccinology enables characterization of mechanisms of action, these tools have yet to be applied to infants, who are at high risk of infection and receive the most vaccines. Bacille Calmette-Guérin (BCG) protects infants against disseminated tuberculosis (TB) and TB-unrelated infections via incompletely understood mechanisms. We employ mass-spectrometry-based metabolomics of blood plasma to profile BCG-induced infant responses in Guinea-Bissau in vivo and the US in vitro. BCG-induced lysophosphatidylcholines (LPCs) correlate with both TLR-agonist- and purified protein derivative (PPD, mycobacterial antigen)-induced blood cytokine production in vitro, raising ...


The Future Of Targeted Kinase Inhibitors In Melanoma, Signe Caksa, Usman Baqai, A E Aplin May 2022

The Future Of Targeted Kinase Inhibitors In Melanoma, Signe Caksa, Usman Baqai, A E Aplin

Department of Cancer Biology Faculty Papers

Melanoma is a cancer of the pigment-producing cells of the body and its incidence is rising. Targeted inhibitors that act against kinases in the MAPK pathway are approved for BRAF-mutant metastatic cutaneous melanoma and increase patients' survival. Response to these therapies is limited by drug resistance and is less durable than with immune checkpoint inhibition. Conversely, rare melanoma subtypes have few therapeutic options for advanced disease and MAPK pathway targeting agents show minimal anti-tumor effects. Nevertheless, there is a future for targeted kinase inhibitors in melanoma: in new applications such as adjuvant or neoadjuvant therapy and in novel combinations with ...


A Rapid Systematic Review Of Health Literacy In The African American Population Related To Hypertension And Efforts To Address This Public Health Issue, Jimar Hill May 2022

A Rapid Systematic Review Of Health Literacy In The African American Population Related To Hypertension And Efforts To Address This Public Health Issue, Jimar Hill

Master of Public Health Capstone Presentations

Cardiovascular disease is the leading cause of death in the United States. Approximately 660,000 people in the United States die from cardiovascular disease each year. High blood pressure or hypertension can increase the risk of cardiovascular related mortality. High blood pressure may not have any symptoms noticed by an individual, so it is not always clear that someone has this condition. So, it is a public health issue to pursue public health interventions to raise awareness and understanding. In doing so, it is important to understand that the prevalence of hypertension varies among racial and ethnic populations. For example ...


Recommendations For Effective Documentation In Regional Anesthesia: An Expert Panel Delphi Consensus Project, Hassan M Ahmed, Benjamin P Atterton, Gillian G Crowe, Jaime L Barratta, Mark Johnson, Eugene R. Viscusi, Sanjib Adhikary, Eric Albrecht, Karen Boretsky, Jan Boublik, Dara S Breslin, Kelly Byrne, Alan Ch'ng, Alwin Chuan, Patrick Conroy, Craig Daniel, Andrzej Daszkiewicz, Alain Delbos, Dan Sebastian Dirzu, Dmytro Dmytriiev, Paul Fennessy, H Barrie J Fischer, Henry Frizelle, Jeff Gadsden, Philippe Gautier, Rajnish K Gupta, Yavuz Gürkan, Harold David Hardman, William Harrop-Griffiths, Peter Hebbard, Nadia Hernandez, Jakub Hlasny, Gabriella Iohom, Vivian H Y Ip, Christina L Jeng, Rebecca L Johnson, Hari Kalagara, Brian Kinirons, Andrew Kenneth Lansdown, Jody C Leng, Yean Chin Lim, Clara Lobo, Danielle B Ludwin, Alan James Robert Macfarlane, Anthony T Machi, Padraig Mahon, Stephen Mannion, David H Mcleod, Peter Merjavy, Aleksejs Miscuks, Christopher H Mitchell, Eleni Moka, Peter Moran, Ann Ngui, Olga C Nin, Brian D O'Donnell, Amit Pawa, Anahi Perlas, Steven Porter, John-Paul Pozek, Humberto C Rebelo, Vicente Roqués, Kristopher M Schroeder, Gary Schwartz, Eric S. Schwenk, Luc Sermeus, George Shorten, Karthikeyan Srinivasan, Markus F Stevens, Kassiani Theodoraki, Lloyd R Turbitt, Luis Fernando Valdés-Vilches, Thomas Volk, Katrina Webster, T Wiesmann, Sylvia H Wilson, Morné Wolmarans, Glenn Woodworth, Andrew K Worek, E M Louise Moran May 2022

Recommendations For Effective Documentation In Regional Anesthesia: An Expert Panel Delphi Consensus Project, Hassan M Ahmed, Benjamin P Atterton, Gillian G Crowe, Jaime L Barratta, Mark Johnson, Eugene R. Viscusi, Sanjib Adhikary, Eric Albrecht, Karen Boretsky, Jan Boublik, Dara S Breslin, Kelly Byrne, Alan Ch'ng, Alwin Chuan, Patrick Conroy, Craig Daniel, Andrzej Daszkiewicz, Alain Delbos, Dan Sebastian Dirzu, Dmytro Dmytriiev, Paul Fennessy, H Barrie J Fischer, Henry Frizelle, Jeff Gadsden, Philippe Gautier, Rajnish K Gupta, Yavuz Gürkan, Harold David Hardman, William Harrop-Griffiths, Peter Hebbard, Nadia Hernandez, Jakub Hlasny, Gabriella Iohom, Vivian H Y Ip, Christina L Jeng, Rebecca L Johnson, Hari Kalagara, Brian Kinirons, Andrew Kenneth Lansdown, Jody C Leng, Yean Chin Lim, Clara Lobo, Danielle B Ludwin, Alan James Robert Macfarlane, Anthony T Machi, Padraig Mahon, Stephen Mannion, David H Mcleod, Peter Merjavy, Aleksejs Miscuks, Christopher H Mitchell, Eleni Moka, Peter Moran, Ann Ngui, Olga C Nin, Brian D O'Donnell, Amit Pawa, Anahi Perlas, Steven Porter, John-Paul Pozek, Humberto C Rebelo, Vicente Roqués, Kristopher M Schroeder, Gary Schwartz, Eric S. Schwenk, Luc Sermeus, George Shorten, Karthikeyan Srinivasan, Markus F Stevens, Kassiani Theodoraki, Lloyd R Turbitt, Luis Fernando Valdés-Vilches, Thomas Volk, Katrina Webster, T Wiesmann, Sylvia H Wilson, Morné Wolmarans, Glenn Woodworth, Andrew K Worek, E M Louise Moran

Department of Anesthesiology Faculty Papers

Background and objectives: Documentation is important for quality improvement, education, and research. There is currently a lack of recommendations regarding key aspects of documentation in regional anesthesia. The aim of this study was to establish recommendations for documentation in regional anesthesia.

Methods: Following the formation of the executive committee and a directed literature review, a long list of potential documentation components was created. A modified Delphi process was then employed to achieve consensus amongst a group of international experts in regional anesthesia. This consisted of 2 rounds of anonymous electronic voting and a final virtual round table discussion with live ...


Arthroscopically Assisted Acromioclavicular And Coracoclavicular Reconstruction With A Looped Braided Polyester Suture Band And Buckle Device., Kurt E Stoll, Benjamin Hendy, Treg Brown, Nathaniel Cohen, Thay Q Lee, Surena Namdari, Phil Davidson May 2022

Arthroscopically Assisted Acromioclavicular And Coracoclavicular Reconstruction With A Looped Braided Polyester Suture Band And Buckle Device., Kurt E Stoll, Benjamin Hendy, Treg Brown, Nathaniel Cohen, Thay Q Lee, Surena Namdari, Phil Davidson

Rothman Institute Faculty Papers

Acromioclavicular (AC) joint injuries occur with a traumatic load to the lateral aspect of the shoulder and account for 9% of all shoulder girdle injuries. Rockwood classified AC joint injuries as type I though type VI, based on severity of injury, radiographic findings, and reducibility of the AC joint. Type I and II injuries are typically managed nonoperatively, whereas type IV, V, and VI are managed operatively to address the significant soft tissue disruption, persistent AC joint instability, and apical shoulder deformation. Treatment of type III injuries remain controversial. Several techniques have been described to treat AC joint injuries with ...


Impact Of Homologous Recombination Status And Responses With Veliparib Combined With First-Line Chemotherapy In Ovarian Cancer In The Phase 3 Velia/Gog-3005 Study, Elizabeth M Swisher, Carol Aghajanian, David M O'Malley, Gini F Fleming, Scott H Kaufmann, Douglas A Levine, Michael J Birrer, Kathleen N Moore, Nick M Spirtos, Mark S Shahin, Thomas J Reid, Michael Friedlander, Karina Dahl Steffensen, Aikou Okamoto, Vasudha Sehgal, Peter J Ansell, Minh H Dinh, Michael A Bookman, Robert L Coleman May 2022

Impact Of Homologous Recombination Status And Responses With Veliparib Combined With First-Line Chemotherapy In Ovarian Cancer In The Phase 3 Velia/Gog-3005 Study, Elizabeth M Swisher, Carol Aghajanian, David M O'Malley, Gini F Fleming, Scott H Kaufmann, Douglas A Levine, Michael J Birrer, Kathleen N Moore, Nick M Spirtos, Mark S Shahin, Thomas J Reid, Michael Friedlander, Karina Dahl Steffensen, Aikou Okamoto, Vasudha Sehgal, Peter J Ansell, Minh H Dinh, Michael A Bookman, Robert L Coleman

Kimmel Cancer Center Faculty Papers

Objective: In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status. Here, we report exploratory analyses of the impact of homologous recombination deficient (HRD) or proficient (HRP) status on progression-free survival (PFS) and objective response rates during chemotherapy.

Methods: Women with Stage III-IV ovarian carcinoma were randomized to veliparib-throughout, veliparib-combination-only, or placebo. Stratification factors included timing of surgery and germline BRCA mutation status. HRD status was dichotomized at genomic instability score 33. During combination therapy, CA-125 levels ...


Peripheral Neuropathy Evaluations Of Patients With Prolonged Long Covid., Anne Louise Oaklander, Alexander J Mills, Mary Kelley, Lisa S Toran, Bryan Smith, Marinos Dalakas, Avindra Nath May 2022

Peripheral Neuropathy Evaluations Of Patients With Prolonged Long Covid., Anne Louise Oaklander, Alexander J Mills, Mary Kelley, Lisa S Toran, Bryan Smith, Marinos Dalakas, Avindra Nath

Department of Neurology Faculty Papers

Background and objectives: Recovery from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears exponential, leaving a tail of patients reporting various long COVID symptoms including unexplained fatigue/exertional intolerance and dysautonomic and sensory concerns. Indirect evidence links long COVID to incident polyneuropathy affecting the small-fiber (sensory/autonomic) axons.

Methods: We analyzed cross-sectional and longitudinal data from patients with World Health Organization (WHO)-defined long COVID without prior neuropathy history or risks who were referred for peripheral neuropathy evaluations. We captured standardized symptoms, examinations, objective neurodiagnostic test results, and outcomes, tracking participants for 1.4 years on average.

Results: Among ...


Age Moderates The Effect Of Injury Severity On Functional Trajectories In Traumatic Brain Injury: A Study Using The Nidilrr Traumatic Brain Injury Model Systems National Dataset., Laraine Winter, Janell L Mensinger, Helene J Moriarty, Keith M Robinson, Michelle Mckay, Benjamin E Leiby Apr 2022

Age Moderates The Effect Of Injury Severity On Functional Trajectories In Traumatic Brain Injury: A Study Using The Nidilrr Traumatic Brain Injury Model Systems National Dataset., Laraine Winter, Janell L Mensinger, Helene J Moriarty, Keith M Robinson, Michelle Mckay, Benjamin E Leiby

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Age is a risk factor for a host of poor outcomes following traumatic brain injury (TBI), with some evidence suggesting that age is also a source of excess disability. We tested the extent to which age moderates the effect of injury severity on functional trajectories over 15 years post injury. Data from 11,442 participants from the 2020 National Institute of Disability and Independent Living Rehabiitation Research (NIDILRR) Traumatic Brain Injury Model Systems (TBIMS) National Dataset were analyzed using linear mixed effects models. Injury severity was operationally defined using a composite of Glasgow Coma Scale scores, structural imaging findings, and ...


Heterozygous Frameshift Variants In Hnrnpa2b1 Cause Early-Onset Oculopharyngeal Muscular Dystrophy, Hong Joo Kim, Payam Mohassel, Sandra Donkervoort, Lin Guo, Kevin O'Donovan, Maura Coughlin, Xaviere Lornage, Nicola Foulds, Simon R Hammans, A Reghan Foley, Charlotte M Fare, Alice F Ford, Masashi Ogasawara, Aki Sato, Aritoshi Iida, Pinki Munot, Gautam Ambegaonkar, Rahul Phadke, Dominic G O'Donovan, Rebecca Buchert, Mona Grimmel, Ana Töpf, Irina T Zaharieva, Lauren Brady, Ying Hu, Thomas E Lloyd, Andrea Klein, Maja Steinlin, Alice Kuster, Sandra Mercier, Pascale Marcorelles, Yann Péréon, Emmanuelle Fleurence, Adnan Manzur, Sarah Ennis, Rosanna Upstill-Goddard, Luca Bello, Cinzia Bertolin, Elena Pegoraro, Leonardo Salviati, Courtney E French, Andriy Shatillo, F Lucy Raymond, Tobias B Haack, Susana Quijano-Roy, Johann Böhm, Isabelle Nelson, Tanya Stojkovic, Teresinha Evangelista, Volker Straub, Norma B Romero, Jocelyn Laporte, Francesco Muntoni, Ichizo Nishino, Mark A Tarnopolsky, James Shorter, Carsten G Bönnemann, J Paul Taylor Apr 2022

Heterozygous Frameshift Variants In Hnrnpa2b1 Cause Early-Onset Oculopharyngeal Muscular Dystrophy, Hong Joo Kim, Payam Mohassel, Sandra Donkervoort, Lin Guo, Kevin O'Donovan, Maura Coughlin, Xaviere Lornage, Nicola Foulds, Simon R Hammans, A Reghan Foley, Charlotte M Fare, Alice F Ford, Masashi Ogasawara, Aki Sato, Aritoshi Iida, Pinki Munot, Gautam Ambegaonkar, Rahul Phadke, Dominic G O'Donovan, Rebecca Buchert, Mona Grimmel, Ana Töpf, Irina T Zaharieva, Lauren Brady, Ying Hu, Thomas E Lloyd, Andrea Klein, Maja Steinlin, Alice Kuster, Sandra Mercier, Pascale Marcorelles, Yann Péréon, Emmanuelle Fleurence, Adnan Manzur, Sarah Ennis, Rosanna Upstill-Goddard, Luca Bello, Cinzia Bertolin, Elena Pegoraro, Leonardo Salviati, Courtney E French, Andriy Shatillo, F Lucy Raymond, Tobias B Haack, Susana Quijano-Roy, Johann Böhm, Isabelle Nelson, Tanya Stojkovic, Teresinha Evangelista, Volker Straub, Norma B Romero, Jocelyn Laporte, Francesco Muntoni, Ichizo Nishino, Mark A Tarnopolsky, James Shorter, Carsten G Bönnemann, J Paul Taylor

Department of Biochemistry and Molecular Biology Faculty Papers

Missense variants in RNA-binding proteins (RBPs) underlie a spectrum of disease phenotypes, including amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy. Here, we present ten independent families with a severe, progressive muscular dystrophy, reminiscent of oculopharyngeal muscular dystrophy (OPMD) but of much earlier onset, caused by heterozygous frameshift variants in the RBP hnRNPA2/B1. All disease-causing frameshift mutations abolish the native stop codon and extend the reading frame, creating novel transcripts that escape nonsense-mediated decay and are translated to produce hnRNPA2/B1 protein with the same neomorphic C-terminal sequence. In contrast to previously reported disease-causing missense variants in HNRNPA2B1 ...


Enpp1 Variants In Patients With Gaci And Pxe Expand The Clinical And Genetic Heterogeneity Of Heritable Disorders Of Ectopic Calcification., Douglas Ralph, Yvonne Nitschke, Michael A Levine, Matthew Caffet, Tamara Wurst, Amir Hossein Saeidian, Leila Youssefian, Hassan Vahidnezhad, Sharon F Terry, Frank Rutsch, Jouni Uitto, Qiaoli Li Apr 2022

Enpp1 Variants In Patients With Gaci And Pxe Expand The Clinical And Genetic Heterogeneity Of Heritable Disorders Of Ectopic Calcification., Douglas Ralph, Yvonne Nitschke, Michael A Levine, Matthew Caffet, Tamara Wurst, Amir Hossein Saeidian, Leila Youssefian, Hassan Vahidnezhad, Sharon F Terry, Frank Rutsch, Jouni Uitto, Qiaoli Li

Department of Medicine Faculty Papers

Pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy (GACI) are clinically distinct genetic entities of ectopic calcification associated with differentially reduced circulating levels of inorganic pyrophosphate (PPi), a potent endogenous inhibitor of calcification. Variants in ENPP1, the gene mutated in GACI, have not been associated with classic PXE. Here we report the clinical, laboratory, and molecular evaluations of ten GACI and two PXE patients from five and two unrelated families registered in GACI Global and PXE International databases, respectively. All patients were found to carry biallelic variants in ENPP1. Among ten ENPP1 variants, one homozygous variant demonstrated uniparental disomy ...


Selective Axonal Transport Through Branch Junctions Is Directed By Growth Cone Signaling And Mediated By Kif1/Kinesin-3 Motors., Stephen R. Tymanskyj, Bridget M. Curran, Le Ma Apr 2022

Selective Axonal Transport Through Branch Junctions Is Directed By Growth Cone Signaling And Mediated By Kif1/Kinesin-3 Motors., Stephen R. Tymanskyj, Bridget M. Curran, Le Ma

Department of Neuroscience Faculty Papers

Development and function of nerve cells rely on the orchestration of microtubule-based transport from the cell body into distal axonal terminals. Neurons often have highly elaborate branches innervating multiple targets, but how protein or membrane cargos navigate through branch junctions to specific branch targets is unknown. Here, we demonstrate that anterograde transport of membrane vesicles through axonal branch junctions is highly selective, which is influenced by branch length and more strongly by growth cone motility. Using an optogenetic tool, we demonstrate that signaling from the growth cone can rapidly direct transport through branch junctions. We further demonstrate that such transport ...


A Periplasmic Cinched Protein Is Required For Siderophore Secretion And Virulence Of Mycobacterium Tuberculosis., Lei Zhang, James E Kent, Meredith Whitaker, David C Young, Dominik Herrmann, Alexander E Aleshin, Ying-Hui Ko, Gino Cingolani, Jamil S Saad, D Branch Moody, Francesca M Marassi, Sabine Ehrt, Michael Niederweis Apr 2022

A Periplasmic Cinched Protein Is Required For Siderophore Secretion And Virulence Of Mycobacterium Tuberculosis., Lei Zhang, James E Kent, Meredith Whitaker, David C Young, Dominik Herrmann, Alexander E Aleshin, Ying-Hui Ko, Gino Cingolani, Jamil S Saad, D Branch Moody, Francesca M Marassi, Sabine Ehrt, Michael Niederweis

Department of Biochemistry and Molecular Biology Faculty Papers

Iron is essential for growth of Mycobacterium tuberculosis, the causative agent of tuberculosis. To acquire iron from the host, M. tuberculosis uses the siderophores called mycobactins and carboxymycobactins. Here, we show that the rv0455c gene is essential for M. tuberculosis to grow in low-iron medium and that secretion of both mycobactins and carboxymycobactins is drastically reduced in the rv0455c deletion mutant. Both water-soluble and membrane-anchored Rv0455c are functional in siderophore secretion, supporting an intracellular role. Lack of Rv0455c results in siderophore toxicity, a phenotype observed for other siderophore secretion mutants, and severely impairs replication of M. tuberculosis in mice, demonstrating ...


Effect Of Lipid-Lowering Medications In Patients With Coronary Artery Bypass Grafting Surgery Outcomes, Chunxia Shi, Zugui Zhang, Jordan E Goldhammer, David Li, Bob Kiaii, Victor Rudriguez, Douglas Boyd, David Lubarsky, Richard Applegate, Hong Liu Apr 2022

Effect Of Lipid-Lowering Medications In Patients With Coronary Artery Bypass Grafting Surgery Outcomes, Chunxia Shi, Zugui Zhang, Jordan E Goldhammer, David Li, Bob Kiaii, Victor Rudriguez, Douglas Boyd, David Lubarsky, Richard Applegate, Hong Liu

Department of Anesthesiology Faculty Papers

Background: Increased life expectancy and improved medical technology allow increasing numbers of elderly patients to undergo cardiac surgery. Elderly patients may be at greater risk of postoperative morbidity and mortality. Complications can lead to worsened quality of life, shortened life expectancy and higher healthcare costs. Reducing perioperative complications, especially severe adverse events, is key to improving outcomes in patients undergoing cardiac surgery. The objective of this study is to determine whether perioperative lipid-lowering medication use is associated with a reduced risk of complications and mortality after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB).

Methods: After IRB approval, we ...


Analyzing The Effect Of Interview Time And Day On Emergency Medicine Residency Interview Scores, Alanna O'Connell, Sean Greco, Tingting Zhan, Tracy Brader, Megan Crossman, Robin Naples, Anthony Sielicki, Megan Stobart Gallagher, Peter Tomaselli, Dimitrios Papanagnou Apr 2022

Analyzing The Effect Of Interview Time And Day On Emergency Medicine Residency Interview Scores, Alanna O'Connell, Sean Greco, Tingting Zhan, Tracy Brader, Megan Crossman, Robin Naples, Anthony Sielicki, Megan Stobart Gallagher, Peter Tomaselli, Dimitrios Papanagnou

Department of Medicine Faculty Papers

Background: When it comes to scheduling interviews, medical students may wonder if they need a strategy to increase their likelihood of matching. Previous studies examined the temporal effects of the residency interview on overall match rate; however, there are additional factors that affect the match process, including board examination scores and letters of recommendation. Only few studies have examined the effect interview time of day has on match success. The current study examines the impact date and time of interview during the interview season have on candidates' respective interview scores.

Methods: Interview data over a three-year period (i.e., three ...


Cyclophosphamide Induces Durable Molecular And Clinical Responses In Patients With Relapsed T-Lgl Leukemia., Zachary Braunstein, Eric Mclaughlin, Anjali Mishra, Jonathan E Brammer Apr 2022

Cyclophosphamide Induces Durable Molecular And Clinical Responses In Patients With Relapsed T-Lgl Leukemia., Zachary Braunstein, Eric Mclaughlin, Anjali Mishra, Jonathan E Brammer

Department of Medical Oncology Faculty Papers

No abstract provided.


Development And Preclinical Investigation Of Physically Cross-Linked And Ph-Sensitive Polymeric Gels As Potential Vaginal Contraceptives, Ankit K. Rochani, Vivek Agrahari, Neelima Chandra, Onkar N Singh, Timothy J Mccormick, Gustavo F Doncel, Meredith R Clark, Gagan Kaushal Apr 2022

Development And Preclinical Investigation Of Physically Cross-Linked And Ph-Sensitive Polymeric Gels As Potential Vaginal Contraceptives, Ankit K. Rochani, Vivek Agrahari, Neelima Chandra, Onkar N Singh, Timothy J Mccormick, Gustavo F Doncel, Meredith R Clark, Gagan Kaushal

Department of Pharmacology and Experimental Therapeutics Faculty Papers

This study explored the development of cross-linked gels to potentially provide a physical barrier to vaginal sperm transport for contraception. Two types of gels were formulated, a physically cross-linked iota-carrageenan (Ci) phenylboronic acid functionalized hydroxylpropylmethyacrylate copolymer (PBA)-based (Ci-PBA) gel, designed to block vaginal sperm transport. The second gel was pH-shifting cross-linked Ci-polyvinyl alcohol-boric acid (Ci-PVA-BA) gel, designed to modulate its properties in forming a viscoelastic, weakly cross-linked transient network (due to Ci gelling properties) on vaginal application (at acidic pH of ~3.5-4.5) to a more elastic, densely cross-linked (due to borate-diol cross-linking) gel network at basic pH ...