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Full-Text Articles in Therapeutics

Microbubble-Protected Oncolytic Virotherapy Targeted By Sonoporation Induces Tumor Necrosis And T-Lymphocyte Infiltration In Humanized Mice Bearing Triple-Negative Breast Cancer, Juliana Sitta, Flavia De Carlo, Imani Kirven, John H. Tackett, Patrice Penfornis, George Clement Dobbins, Mallory Barbier, Luis Del Valle, Clayton T. Larsen, Ernest G. Schutt, Rhodemann Li, Candace M. Howard, Pier Paolo Claudio Dec 2024

Microbubble-Protected Oncolytic Virotherapy Targeted By Sonoporation Induces Tumor Necrosis And T-Lymphocyte Infiltration In Humanized Mice Bearing Triple-Negative Breast Cancer, Juliana Sitta, Flavia De Carlo, Imani Kirven, John H. Tackett, Patrice Penfornis, George Clement Dobbins, Mallory Barbier, Luis Del Valle, Clayton T. Larsen, Ernest G. Schutt, Rhodemann Li, Candace M. Howard, Pier Paolo Claudio

School of Medicine Faculty Publications

Oncolytic virotherapy has shown great promise in mediating targeted tumor destruction through tumor-selective replication and induction of anti-tumor immunity; however, obstacles remain for virus candidates to reach the clinic. These include avoiding neutralizing antibodies, preventing stimulation of the adaptive immune response during intravenous administration, and inducing sufficient apoptosis and immune activation so that the body's defense can work to eradicate systemic disease. We have developed a co-formulation of oncolytic viruses (OVs) with Imagent lipid-encapsulated, perfluorocarbon microbubbles (MBs) to protect the OVs from the innate and adaptive immune system. Once inside the MB, the viral particles become acoustically active such that …


Glucagon-Like Peptide-1 Receptor Agonist Mediated Weight Loss And Diabetes Mellitus Benefits: A Narrative Review, Alan D. Kaye, Nathan Lien, Christopher Vuong, Matthew H. Schmitt, Yusra Soorya, Bushirat A. Abubakar, Luke Muiznieks, Noah Embry, Harish Siddaiah, Adam M. Kaye, Sahar Shekoohi, Giustino Varrassi Dec 2024

Glucagon-Like Peptide-1 Receptor Agonist Mediated Weight Loss And Diabetes Mellitus Benefits: A Narrative Review, Alan D. Kaye, Nathan Lien, Christopher Vuong, Matthew H. Schmitt, Yusra Soorya, Bushirat A. Abubakar, Luke Muiznieks, Noah Embry, Harish Siddaiah, Adam M. Kaye, Sahar Shekoohi, Giustino Varrassi

School of Medicine Faculty Publications

Obesity and type 2 diabetes mellitus (T2DM) are chronic diseases with increasing prevalence, underscoring the urgent need for effective treatment and management strategies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as an essential class of drugs for managing both obesity and T2DM, offering additional benefits for cardiovascular and kidney health. GLP-1 RAs work by targeting GLP-1 receptors, mimicking the effects of the natural hormone GLP-1 to regulate blood glucose levels, promote weight loss, and provide potential benefits for cardiovascular health. This narrative review evaluates the mechanisms of action, clinical efficacy, and broader roles of GLP-1 RAs in promoting weight …


Innovations In Genicular Outcomes Registry (Igor): Protocol For A Real-World Registry Study Of Treatments For Knee Osteoarthritis, Vinod Dasa, William Mihalko, Adam Rivadeneyra, Joshua Urban, Andrew Wickline, David Rogenmoser, Andrew Concoff, Andrew Spitzer, Michael A. Mont Dec 2024

Innovations In Genicular Outcomes Registry (Igor): Protocol For A Real-World Registry Study Of Treatments For Knee Osteoarthritis, Vinod Dasa, William Mihalko, Adam Rivadeneyra, Joshua Urban, Andrew Wickline, David Rogenmoser, Andrew Concoff, Andrew Spitzer, Michael A. Mont

School of Medicine Faculty Publications

BACKGROUND: Osteoarthritis (OA) is the leading cause of disability among US adults and most commonly affects the knee. Guidelines for knee OA treatment include behavioral, nonpharmacological, pharmacological, and surgical interventions. While emerging knee OA treatments show promise for pain control, data gaps remain regarding the efficacy, safety, comparative effectiveness, and real-world value of treatments. OBJECTIVES: The Innovations in Genicular Outcomes Registry (IGOR) is prospectively collecting real-world data to assess clinical effectiveness, safety, health-related quality of life, and healthcare resource utilization of knee OA treatments. DESIGN: The IGOR is a prospective, observational, longitudinal, multicenter registry (NCT05495334) examining knee OA pain treatment …


Enhancing Immune Response And Survival In Hepatocellular Carcinoma With Novel Oncolytic Jurona Virus And Immune Checkpoint Blockade, Mulu Z. Tesfay, Yuguo Zhang, Khandoker U. Ferdous, Mika A. Taylor, Aleksandra Cios, Randal S. Shelton, Camila C. Simoes, Chelsae R. Watters, Oumar Barro, Natalie M. Elliott, Bahaa Mustafa, Jean Christopher Chamcheu, Alicia L. Graham, Charity L. Washam, Duah Alkam, Allen Gies, Stephanie D. Byrum, Emmanouil Giorgakis, Steven R. Post, Thomas Kelly, Jun Ying, Omeed Moaven, Chiswili Y. Chabu, Martin E. Fernandez-Zapico, Dan G. Duda, Lewis R. Roberts, Rang Govindarajan, Mitesh J. Borad, Martin J. Cannon, Et Al Nov 2024

Enhancing Immune Response And Survival In Hepatocellular Carcinoma With Novel Oncolytic Jurona Virus And Immune Checkpoint Blockade, Mulu Z. Tesfay, Yuguo Zhang, Khandoker U. Ferdous, Mika A. Taylor, Aleksandra Cios, Randal S. Shelton, Camila C. Simoes, Chelsae R. Watters, Oumar Barro, Natalie M. Elliott, Bahaa Mustafa, Jean Christopher Chamcheu, Alicia L. Graham, Charity L. Washam, Duah Alkam, Allen Gies, Stephanie D. Byrum, Emmanouil Giorgakis, Steven R. Post, Thomas Kelly, Jun Ying, Omeed Moaven, Chiswili Y. Chabu, Martin E. Fernandez-Zapico, Dan G. Duda, Lewis R. Roberts, Rang Govindarajan, Mitesh J. Borad, Martin J. Cannon, Et Al

School of Medicine Faculty Publications

Members of the Vesiculovirus genus including Jurona virus (JURV) have emerged as promising immunotherapeutic agents, characterized by their tumor selectivity, fast kinetics, low seroprevalence, and minimal toxicity in humans. Here, we demonstrate that the administration of JURV leads to tumor regression in both hepatocellular carcinoma (HCC) xenograft and syngeneic models. Furthermore, our findings indicate that combining JURV and anti-PD-1 therapy reduced tumor burden and improved survival rates over JURV or anti-PD-1 alone in an orthotopic HCC model. Proteogenomic analysis of JURV-treated, murine HCC tumors demonstrates that the therapeutic effects of the combination of JURV and anti-PD-1 are predominantly driven by …


Transcutaneous Electrical Nerve Stimulation For Prevention And Treatment Of Post-Herpetic Neuralgia: A Narrative Review, Alan D. Kaye, Rahib K. Islam, Victoria T. Tong, Brynne E. Tynes, Kelly R. Sala, Brennan Abbott, Chandni R. Patel, Isabella B. Lentz, Raju Behara, Shilpadevi Patil, Uzayr Wasif, Sahar Shekoohi, Giustino Varrassi Nov 2024

Transcutaneous Electrical Nerve Stimulation For Prevention And Treatment Of Post-Herpetic Neuralgia: A Narrative Review, Alan D. Kaye, Rahib K. Islam, Victoria T. Tong, Brynne E. Tynes, Kelly R. Sala, Brennan Abbott, Chandni R. Patel, Isabella B. Lentz, Raju Behara, Shilpadevi Patil, Uzayr Wasif, Sahar Shekoohi, Giustino Varrassi

School of Medicine Faculty Publications

The present investigation evaluated transcutaneous electrical nerve stimulation (TENS) for the non-pharmacological treatment of post-herpetic neuralgia (PHN). PHN is the most common complication of the Herpes Zoster virus, affecting one in every five patients with shingles, and presents as intense neuropathic pain that can persist for 90 days or longer after the initial onset of symptoms. Current pharmacological treatment options are mainly limited to symptom management, including oral medications such as tricyclic antidepressants and gabapentinoid preparations, as well as topical options such as lidocaine or capsaicin. TENS is a minimally invasive, non-pharmacological electrical nerve stimulation device currently approved for the …


Normalization Of Cystic Fibrosis Immune System Reverses Intestinal Neutrophilic Inflammation And Significantly Improves The Survival Of Cystic Fibrosis Mice, Callie E. Scull, Yawen Hu, Scott Jennings, Guoshun Wang Nov 2024

Normalization Of Cystic Fibrosis Immune System Reverses Intestinal Neutrophilic Inflammation And Significantly Improves The Survival Of Cystic Fibrosis Mice, Callie E. Scull, Yawen Hu, Scott Jennings, Guoshun Wang

School of Medicine Faculty Publications

BACKGROUND & AIMS: Cystic fibrosis (CF) is an autosomal recessive genetic disorder, affecting multiple organ systems. CF intestinal disease develops early, manifesting as intestinal bacterial overgrowth/dysbiosis, neutrophilic inflammation, and obstruction. As unresolvable infection and inflammation reflect host immune deficiency, we sought to determine if the CF-affected immune system plays any significant role in CF intestinal disease pathogenesis. METHODS: CF and sibling wild-type (WT) mice underwent reciprocal bone marrow transplantation. After immune reconstitution, their mortality, intestinal transit, fecal inflammatory markers, and mucosal immune cell composition were assessed. Moreover, reciprocal neutrophil transfusion was conducted to determine if neutrophil function affects intestinal movement. …


Guidelines For The Prevention, Diagnosis, And Management Of Urinary Tract Infections In Pediatrics And Adults: A Wikiguidelines Group Consensus Statement, Zachary Nelson, Abdullah Tarik Aslan, Nathan P. Beahm, Michelle Blyth, Matthew Cappiello, Danielle Casaus, Fernando Dominguez, Susan Egbert, Alexandra Hanretty, Tina Khadem, Katie Olney, Ahmed Abdul-Azim, Gloria Aggrey, Daniel T. Anderson, Mariana Barosa, Michael Bosco, Elias B. Chahine, Souradeep Chowdhury, Alyssa Christensen, Daniela De Lima Corvino, Margaret Fitzpatrick, Molly Fleece, Brent Footer, Emily Fox, Bassam Ghanem, Fergus Hamilton, Justin Hayes, Boris Jegorovic, Philipp Jent, Et Al Nov 2024

Guidelines For The Prevention, Diagnosis, And Management Of Urinary Tract Infections In Pediatrics And Adults: A Wikiguidelines Group Consensus Statement, Zachary Nelson, Abdullah Tarik Aslan, Nathan P. Beahm, Michelle Blyth, Matthew Cappiello, Danielle Casaus, Fernando Dominguez, Susan Egbert, Alexandra Hanretty, Tina Khadem, Katie Olney, Ahmed Abdul-Azim, Gloria Aggrey, Daniel T. Anderson, Mariana Barosa, Michael Bosco, Elias B. Chahine, Souradeep Chowdhury, Alyssa Christensen, Daniela De Lima Corvino, Margaret Fitzpatrick, Molly Fleece, Brent Footer, Emily Fox, Bassam Ghanem, Fergus Hamilton, Justin Hayes, Boris Jegorovic, Philipp Jent, Et Al

School of Medicine Faculty Publications

IMPORTANCE: Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence. OBJECTIVE: To create a clinical guideline for the diagnosis and management of urinary tract infections that addresses the gap between the evidence and recommendation strength. EVIDENCE REVIEW: This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In May 2023, new and existing members were solicited for questions on urinary tract infection prevention, diagnosis, and management. For each topic, literature searches were conducted up until early 2024 in any language. Evidence was …


Hematopoietic Cell Transplant Compared With Standard Care In Adolescents And Young Adults With Sickle Cell Disease, Mark C. Walters, Mary Eapen, Yiwen Liu, Fuad El Rassi, Edmund K. Waller, John E. Levine, John J. Strouse, Joseph H. Antin, Suhag H. Parikh, Nitya Bakshi, Carlton D Dampier, Jennifer J. Jaroscak, Shayla Bergmann, Trish E. Wong, Vamsi K. Kota, Betty Sue Pace, Lazaros J. Lekakis, Premal D. Lulla, Robert Nickel, Kimberly A. Kasow, Uday R. Popat, Wally R. Smith, Lolie C. Yu, Nancy L. Difronzo, Nancy L. Geller, Naynesh Kamani, Elizabeth Sue Klings, Kathryn Hassell, Adam M. Mendizabal, Et Al Oct 2024

Hematopoietic Cell Transplant Compared With Standard Care In Adolescents And Young Adults With Sickle Cell Disease, Mark C. Walters, Mary Eapen, Yiwen Liu, Fuad El Rassi, Edmund K. Waller, John E. Levine, John J. Strouse, Joseph H. Antin, Suhag H. Parikh, Nitya Bakshi, Carlton D Dampier, Jennifer J. Jaroscak, Shayla Bergmann, Trish E. Wong, Vamsi K. Kota, Betty Sue Pace, Lazaros J. Lekakis, Premal D. Lulla, Robert Nickel, Kimberly A. Kasow, Uday R. Popat, Wally R. Smith, Lolie C. Yu, Nancy L. Difronzo, Nancy L. Geller, Naynesh Kamani, Elizabeth Sue Klings, Kathryn Hassell, Adam M. Mendizabal, Et Al

School of Medicine Faculty Publications

Disease-modifying therapies are standard of care (SOC) for sickle cell disease (SCD), but hematopoietic cell transplantation (HCT) has curative potential. We compared outcomes prospectively through 2-years after biologic assignment to a Donor or No Donor (SOC) Arm based on the availability of an HLA-matched sibling or unrelated donor (BMTCTN 1503; NCT02766465). A donor search was commenced after eligibility confirmation. The primary endpoint was the comparison of survival 2 years after biologic assignment between treatment arms. Power calculations required 60 participants on the Donor Arm and 140 on the No Donor Arm to determine if early transplant-related mortality might be balanced …


Hyperbaric Oxygen Therapy In The Atls/Acls Resuscitative Management Of Acutely Ill Or Severely Injured Patients With Severe Anemia: A Review, Keith W. Van Meter Oct 2024

Hyperbaric Oxygen Therapy In The Atls/Acls Resuscitative Management Of Acutely Ill Or Severely Injured Patients With Severe Anemia: A Review, Keith W. Van Meter

School of Medicine Faculty Publications

For short periods, even without the presence of red blood cells, hyperbaric oxygen can safely allow plasma to meet the oxygen delivery requirements of a human at rest. By this means, hyperbaric oxygen, in special instances, may be used as a bridge to lessen blood transfusion requirements. Hyperbaric oxygen, applied intermittently, can readily avert oxygen toxicity while meeting the body's oxygen requirements. In acute injury or illness, accumulated oxygen debt is shadowed by adenosine triphosphate debt. Hyperbaric oxygen efficiently provides superior diffusion distances of oxygen in tissue compared to those provided by breathing normobaric oxygen. Intermittent application of hyperbaric oxygen …


Effect Of Nano2, A Donor Of Nitric Oxide, On Glucose Mediated Oxidative Stress In Pancreaticb-Cells, Kazi Nazrul Islam, Rahib K. Islam, Mohammod B. Rashid, Branson Smith, Safa K. Islam Oct 2024

Effect Of Nano2, A Donor Of Nitric Oxide, On Glucose Mediated Oxidative Stress In Pancreaticb-Cells, Kazi Nazrul Islam, Rahib K. Islam, Mohammod B. Rashid, Branson Smith, Safa K. Islam

School of Medicine Faculty Publications

Annual Meeting of the Endocrine Society, ENDO 2024, June 1 - 4, 2024, Boston, MA


Managing Menopause: The Evolving Role Of Estrogens, Selective Serotonin Reuptake Inhibitors, And Phytoestrogens In Balancing Hormonal Fluctuations, Cassande Besong, Sandy Philippeaux, Ansa Bham, Naicha Gustinvil, Abigayle Castine, Giustino Varrassi, Patricia Sutker, Benjamin C. Miller, Caroline R. Burroughs, Sonja Gennuso, Sahar Shekoohi, Alan D. Kaye Sep 2024

Managing Menopause: The Evolving Role Of Estrogens, Selective Serotonin Reuptake Inhibitors, And Phytoestrogens In Balancing Hormonal Fluctuations, Cassande Besong, Sandy Philippeaux, Ansa Bham, Naicha Gustinvil, Abigayle Castine, Giustino Varrassi, Patricia Sutker, Benjamin C. Miller, Caroline R. Burroughs, Sonja Gennuso, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Menopause is characterized by the cessation of menstruation for 12 consecutive months. In this narrative review, we describe the transitional stages of menopause, clinical presentation, pharmacological management of symptoms, and effects on fluctuating hormone levels. To standardize the stages of menopause, the Stages of Reproductive Aging Workshop + 10 (STRAW+10) system was designed with five distinct categories corresponding to symptom presentation and numerical years. Common clinical presentations consist of vasomotor hot flashes, mood changes, decreased libido, osteoporosis, and genitourinary changes, all of which are associated with changes in hormone levels. Because hormones play a major role in the mechanism of …


Acute Liver Failure Induced By Menopausal Supplement, Rahul Patel, Ahmed Hassan, Hayle Scanlan, Matthew Everwine, Zhiyong Ren, Charles Snyder, Hisham Elgenaidi Sep 2024

Acute Liver Failure Induced By Menopausal Supplement, Rahul Patel, Ahmed Hassan, Hayle Scanlan, Matthew Everwine, Zhiyong Ren, Charles Snyder, Hisham Elgenaidi

School of Medicine Faculty Publications

Drug-induced liver injury is one of the most common causes of acute liver failure in the Western world. Despite discontinuation of the offending agent, it can still tax a grim prognosis. We describe a case of a menopausal woman taking a herbal supplement to relieve hot flashes and bloating. This is the first case report of liver injury from this supplement. She initially presented with mild jaundice and elevated transaminases. Unfortunately, she rapidly progressed to encephalopathy, experienced multiorgan failure, and then died.


The Effectiveness Of The Gnana Laryngeal Mask Airway Ii (Gla-Ii) With Novel Suction Tubing In Gastrointestinal (Gi) Cases, Shahab Ahmadzadeh, Landyn D. Johnson, William T. Barham, James Ilochi, Matthew Fredericks, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye Sep 2024

The Effectiveness Of The Gnana Laryngeal Mask Airway Ii (Gla-Ii) With Novel Suction Tubing In Gastrointestinal (Gi) Cases, Shahab Ahmadzadeh, Landyn D. Johnson, William T. Barham, James Ilochi, Matthew Fredericks, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

INTRODUCTION: The Gnana laryngeal mask airway II (GLA-II) is a supraglottic airway device similar to the classic laryngeal mask airway, except it has an additional suction port. This suction port allows for the removal of secretions and saliva. A previous version of the Gnana laryngeal airway 4 was made of silicone, while this newer version is made of polyvinyl chloride (PVC), which is more affordable. This study aimed to demonstrate the effectiveness and tolerability of this PVC-designed GLA-II and evaluate its ability to suction secretions. METHODS: The prospective cohort study included 100 gastrointestinal (GI) cases to determine the effectiveness and …


Changes In Multimorbidity Among Hospitalized Adults In The Us, Christine Loyd, Lauren Picken, Richelle Sanders, Yue Zhang, Richard E. Kennedy, Cynthia J. Brown Sep 2024

Changes In Multimorbidity Among Hospitalized Adults In The Us, Christine Loyd, Lauren Picken, Richelle Sanders, Yue Zhang, Richard E. Kennedy, Cynthia J. Brown

School of Medicine Faculty Publications

OBJECTIVE: This investigation examines burden of comorbidity measured by the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI) among inpatients based on age, sex, and race. METHODS: Cross-sectional analysis of 2012-2018 US NIS datasets. Participants were inpatients 55y+. ICD-9/10 codes for admitting diagnoses were used to calculate disease burden using the CCI and ECI. Unweighted mean CCI and ECI scores were compared across demographic variables. RESULTS: An increase in mean CCI and ECI scores across age, sex, and races (p < .001) was identified. Compared to the youngest age group (55-59y), all age groups had higher mean CCI and ECI adjusting for time (p < .001). Increases were greatest in older age groups until age 80-84 for CCI and 85-89 for ECI. The female group had lower CCI adjusting for time (p < .001) compared to males. There was no difference between sex groups in mean ECI (p=.409). Compared with the White group, all other race groups had higher mean CCI adjusting for time (p < .001). Black inpatients had the highest CCI followed by Native American inpatients. Findings were similar for ECI, but with no difference between Hispanic and White groups (p=.434). CONCLUSIONS: Growing multimorbidity burden among adult inpatients across age, sex, and race supports the continued need for programs for preventing and reducing multimorbidity, especially among communities that experience health inequity including older, Black, and Native American patients.


Inflammation, Physical Activity, And Disease-Free Survival In Stage Iii Colon Cancer: Calgb/Swog 80702 (Alliance), Justin C. Brown, Chao Ma, Qian Shi, Felix Couture, Philip Kuebler, Pankaj Kumar, Benjamin Tan, Smitha Krishnamurthi, Victor Chang, Richard M. Goldberg, Eileen M. O'Reilly, Anthony F. Shields, Jeffrey A. Meyerhardt Aug 2024

Inflammation, Physical Activity, And Disease-Free Survival In Stage Iii Colon Cancer: Calgb/Swog 80702 (Alliance), Justin C. Brown, Chao Ma, Qian Shi, Felix Couture, Philip Kuebler, Pankaj Kumar, Benjamin Tan, Smitha Krishnamurthi, Victor Chang, Richard M. Goldberg, Eileen M. O'Reilly, Anthony F. Shields, Jeffrey A. Meyerhardt

School of Medicine Faculty Publications

Background: Both inflammation and insufficient physical inactivity contribute to individual-level risk of disease recurrence and death in stage III colon cancer. The extent to which increased inflammatory risk can be offset by sufficient physical activity remains unknown. Methods: This cohort study was nested within the CALGB/SWOG 80702 (Alliance) randomized trial. Inflammatory burden was quantified by high-sensitivity C-reactive protein, interleukin-6, and soluble tumor necrosis factor-α receptor 2 after recovery from tumor resection. Physical activity was measured during and after postoperative chemotherapy. The primary endpoint was disease-free survival. Results: The 3-year disease-free survival rate was 88.4% among patients with low inflammation and …


Transcriptomic Features Associated To Neoadjuvant Chemotherapy Response In Four Molecular Breast Cancer Subtypes, Hedda Michelle Guevara-Nieto, Rafael Parra-Medina, Carlos Alberto Orozca, Alejandro Mejia-Garcia, Jovanny Zabaleta, Liliana Lopez-Kleine, Alba Lucia Combita-Rojas Jul 2024

Transcriptomic Features Associated To Neoadjuvant Chemotherapy Response In Four Molecular Breast Cancer Subtypes, Hedda Michelle Guevara-Nieto, Rafael Parra-Medina, Carlos Alberto Orozca, Alejandro Mejia-Garcia, Jovanny Zabaleta, Liliana Lopez-Kleine, Alba Lucia Combita-Rojas

School of Medicine Faculty Publications

12th Annual Symposium on Global Cancer Research, Virtual, May 5 - 9, 2024


Enhancing Neoadjuvant Virotherapy's Effectiveness By Targeting Stroma To Improve Resectability In Pancreatic Cancer, Khandoker Usran Ferdous, Mulu Z. Tesfay, Aleksandra Cios, Randal S. Shelton, Conner Hartupee, Alicja Urbaniak, Jean Christopher Chamcheu, Michail N. Mavros, Emmanouil Giorgakis, Bahaa Mustafa, Camila C. Simoes, Isabelle R. Miousse, Alexei G. Basnakian, Omeed Moaven, Steven R. Post, Martin J. Cannon, Thomas Kelly, Bolni Marius Nagalo Jul 2024

Enhancing Neoadjuvant Virotherapy's Effectiveness By Targeting Stroma To Improve Resectability In Pancreatic Cancer, Khandoker Usran Ferdous, Mulu Z. Tesfay, Aleksandra Cios, Randal S. Shelton, Conner Hartupee, Alicja Urbaniak, Jean Christopher Chamcheu, Michail N. Mavros, Emmanouil Giorgakis, Bahaa Mustafa, Camila C. Simoes, Isabelle R. Miousse, Alexei G. Basnakian, Omeed Moaven, Steven R. Post, Martin J. Cannon, Thomas Kelly, Bolni Marius Nagalo

School of Medicine Faculty Publications

About one-fourth of patients with pancreatic ductal adenocarcinoma (PDAC) are categorized as borderline resectable (BR) or locally advanced (LA). Chemotherapy and radiation therapy have not yielded the anticipated outcomes in curing patients with BR/LA PDAC. The surgical resection of these tumors presents challenges owing to the unpredictability of the resection margin, involvement of vasculature with the tumor, the likelihood of occult metastasis, a higher ratio of positive lymph nodes, and the relatively larger size of tumor nodules. Oncolytic virotherapy has shown promising activity in preclinical PDAC models. Unfortunately, the desmoplastic stroma within the PDAC tumor microenvironment establishes a barrier, hindering …


The Evolving Use Of Gold Nanoparticles As A Possible Reversal Agent For The Symptoms Of Neurodegenerative Diseases: A Narrative Review, Alan D. Kaye, Kelly R. Sala, Drew Dethloff, Matthew Norton, Corey Moss, Michael J. Plessala, Alyssa G. Derouen, Yair Lopez Torres, Julian Kim, Sridhar Tirumala, Sahar Shekoohi, Giustino Varrassi Jul 2024

The Evolving Use Of Gold Nanoparticles As A Possible Reversal Agent For The Symptoms Of Neurodegenerative Diseases: A Narrative Review, Alan D. Kaye, Kelly R. Sala, Drew Dethloff, Matthew Norton, Corey Moss, Michael J. Plessala, Alyssa G. Derouen, Yair Lopez Torres, Julian Kim, Sridhar Tirumala, Sahar Shekoohi, Giustino Varrassi

School of Medicine Faculty Publications

Neurodegenerative diseases are broadly hallmarked by impaired energy metabolism and toxic intracellular accumulations such as damaged organelles or reactive oxygen species (ROS). Gold nanoparticles readily cross the blood-brain barrier and increase nicotinamide adenine dinucleotide + hydrogen (NADH) oxidation to nicotinamide adenine dinucleotide (NAD+), which is vital for intracellular energy generation, cellular repair, and protection from ROS. Thus, the use of gold nanoparticles to treat and potentially reverse cellular injury seen in neurodegenerative disease has been an area of ongoing research. This systematic review explores current literature regarding the use of gold nanoparticle therapy in the treatment of neurodegenerative diseases such …


Qualitative Interviews Exploring Adverse Event Mitigation Strategies In Adults Receiving Amikacin Liposome Inhalation Suspension, Juzar Ali, Jasmanda Wu, Mariam Hassan, Jui-Hua Tsai, Nancy Touba, Kelly Mccarrier, Mark Ballard, Anjan Chatterjee Jul 2024

Qualitative Interviews Exploring Adverse Event Mitigation Strategies In Adults Receiving Amikacin Liposome Inhalation Suspension, Juzar Ali, Jasmanda Wu, Mariam Hassan, Jui-Hua Tsai, Nancy Touba, Kelly Mccarrier, Mark Ballard, Anjan Chatterjee

School of Medicine Faculty Publications

Introduction: This study aimed to gain insight from patients with refractory Mycobacterium avium complex lung disease (MAC-LD) into strategies used to manage adverse events (AEs) associated with amikacin liposome inhalation suspension (ALIS). Methods: We conducted semi-structured interviews with US patients with refractory MAC-LD prescribed ALIS in a real-world setting. Interview transcripts were analyzed and coded to identify patterns in participants’ descriptions of their ALIS treatment experiences, including AEs and their disruptiveness, and AE mitigation strategies, including participants’ ratings of strategies’ effectiveness. Concept saturation was also assessed. Results: Twenty participants (mean age 48.7 years; 80% women; mean ALIS duration 5.45 months) …


Splenic Artery Embolization In The Treatment Of Blunt Splenic Injury: Single Level 1 Trauma Center Experience, Katelyn Gill, Sarah Aleman, Alexandra H. Fairchild, Bahri Üstünsöz, Dan Laney, Alison A. Smith, Hector Ferral Jul 2024

Splenic Artery Embolization In The Treatment Of Blunt Splenic Injury: Single Level 1 Trauma Center Experience, Katelyn Gill, Sarah Aleman, Alexandra H. Fairchild, Bahri Üstünsöz, Dan Laney, Alison A. Smith, Hector Ferral

School of Medicine Faculty Publications

PURPOSE: To describe the experience of a single level 1 trauma center in the management of blunt splenic injuries (BSI). METHODS: This is a retrospective study with Institutional Review Board approval. The medical records of 450 patients with BSI treated between January 2016 and December 2022 were reviewed. Seventy-two patients were treated with splenic artery embolization (SAE), met the study criteria, and were eligible for data analysis. Spleen injuries were graded in accordance with the American Association for the Surgery of Trauma Organ Injury Scale. Univariate data analysis was performed, with P < 0.05 considered statistically significant. RESULTS: The splenic salvage rate was 90.3% (n = 65/72). Baseline demographics were similar between the groups (P > 0.05). Distal embolization with Gelfoam had similar rates …


Emerging Treatments And Therapies For Autism Spectrum Disorder: A Narrative Review, Alan D. Kaye, Kaitlyn E. Allen, Van S. Smith Iii, Victoria T. Tong, Vivian E. Mire, Huy Nguyen, Zachary Lee, Maria Kouri, Carlo Jean Baptiste, Chizoba N. Mosieri, Adam M. Kaye, Giustino Varrassi, Sahar Shekoohi Jul 2024

Emerging Treatments And Therapies For Autism Spectrum Disorder: A Narrative Review, Alan D. Kaye, Kaitlyn E. Allen, Van S. Smith Iii, Victoria T. Tong, Vivian E. Mire, Huy Nguyen, Zachary Lee, Maria Kouri, Carlo Jean Baptiste, Chizoba N. Mosieri, Adam M. Kaye, Giustino Varrassi, Sahar Shekoohi

School of Medicine Faculty Publications

The prevalence of autism spectrum disorder (ASD) has increased over the last decade. In this regard, many emerging therapies have been described as ASD therapies. Although ASD does not have a cure, there are several management options available that can help reduce symptom severity. ASD is highly variable and, therefore, standard treatment protocols and studies are challenging to perform. Many of these therapies also address comorbidities for which patients with ASD have an increased risk. These concurrent diagnoses can include psychiatric and neurological disorders, including attention deficit and hyperactivity disorder, anxiety disorders, and epilepsy, as well as gastrointestinal symptoms such …


Pro-Resolving Lipid Mediator Reduces Amyloid-Β42-Induced Gene Expression In Human Monocyte-Derived Microglia, Ying Wang, Xiang Zhang, Henrik Biverstål, Nicolas G. Bazan, Shuai Tan, Nailin Li, Makiko Ohshima, Marianne Schultzberg, Xiaofei Li May 2024

Pro-Resolving Lipid Mediator Reduces Amyloid-Β42-Induced Gene Expression In Human Monocyte-Derived Microglia, Ying Wang, Xiang Zhang, Henrik Biverstål, Nicolas G. Bazan, Shuai Tan, Nailin Li, Makiko Ohshima, Marianne Schultzberg, Xiaofei Li

School of Medicine Faculty Publications

JOURNAL/nrgr/04.03/01300535-202503000-00031/figure1/v/2024-06-17T092413Z/r/image-tiff Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte-derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42-induced Alzheimer's disease-like inflammation. Analysis of …


Blastomas Of The Digestive System In Adults: A Review, Yu Liu, Tony El Jabbour, Jonathan Somma, Yukihiro Nakanishi, Saverio Ligato, Hwajeong Lee, Zhi-Yan Fu Apr 2024

Blastomas Of The Digestive System In Adults: A Review, Yu Liu, Tony El Jabbour, Jonathan Somma, Yukihiro Nakanishi, Saverio Ligato, Hwajeong Lee, Zhi-Yan Fu

School of Medicine Faculty Publications

Blastomas, characterized by a mixture of mesenchymal, epithelial, and undifferentiated blastematous components, are rare malignant neoplasms originating from precursor blast cells. This review focuses on digestive system blastomas in adult patients, including gastroblastoma, hepatoblastoma, and pancreatoblastoma. Gastroblastoma is a biphasic, epitheliomesenchymal tumor, with only sixteen cases reported to date. In addition to the characteristic histology, metastasis-associated lung adenocarcinoma transcript 1 - glioma-associated oncogene homolog 1 gene fusion is typical, although recently novel ewing sarcoma breakpoint region 1 - c-terminal binding protein 1 and patched 1 - glioma-associated oncogene homolog 2 fusions have been described. Hepatoblastoma is exceptionally rare in adults …


The Evolving Role Of Monomethyl Fumarate Treatment As Pharmacotherapy For Relapsing-Remitting Multiple Sclerosis, Alan D. Kaye, John Lacey, Viet Le, Ahmed Fazal, Nicole A. Boggio, Dorothy H. Askins, Lillian Anderson, Christopher L. Robinson, Antonella Paladini, Chizoba N. Mosieri, Adam M. Kaye, Shahab Ahmadzadeh, Sahar Shekoohi, Giustino Varrassi Apr 2024

The Evolving Role Of Monomethyl Fumarate Treatment As Pharmacotherapy For Relapsing-Remitting Multiple Sclerosis, Alan D. Kaye, John Lacey, Viet Le, Ahmed Fazal, Nicole A. Boggio, Dorothy H. Askins, Lillian Anderson, Christopher L. Robinson, Antonella Paladini, Chizoba N. Mosieri, Adam M. Kaye, Shahab Ahmadzadeh, Sahar Shekoohi, Giustino Varrassi

School of Medicine Faculty Publications

Multiple sclerosis is the most common autoimmune disease affecting the central nervous system (CNS) worldwide. Multiple sclerosis involves inflammatory demyelination of nerve fibers in the CNS, often presenting with recurrent episodes of focal sensory or motor deficits associated with the region of the CNS affected. The prevalence of this disease has increased rapidly over the last decade. Despite the approval of many new pharmaceutical therapies in the past 20 years, there remains a growing need for alternative therapies to manage the course of this disease. Treatments are separated into two main categories: management of acute flare versus long-term prevention of …


Aortic Stenosis Management In Patients With Acute Hip Fracture, Juan A. Terré, Juan Torrado, Isaac George, Rafael Harari, Pedro R. Cox-Alomar, Pedro A. Villablanca, Robert T. Faillace, Juan F. Granada, George Dangas, Mario J. Garcia, Azeem Latib, José Wiley Apr 2024

Aortic Stenosis Management In Patients With Acute Hip Fracture, Juan A. Terré, Juan Torrado, Isaac George, Rafael Harari, Pedro R. Cox-Alomar, Pedro A. Villablanca, Robert T. Faillace, Juan F. Granada, George Dangas, Mario J. Garcia, Azeem Latib, José Wiley

School of Medicine Faculty Publications

The treatment of severe aortic stenosis (SAS) has evolved rapidly with the advent of minimally invasive structural heart interventions. Transcatheter aortic valve replacement has allowed patients to undergo definitive SAS treatment achieving faster recovery rates compared to valve surgery. Not infrequently, patients are admitted/diagnosed with SAS after a fall associated with a hip fracture (HFx). While urgent orthopedic surgery is key to reduce disability and mortality, untreated SAS increases the perioperative risk and precludes physical recovery. There is no consensus on what the best strategy is either hip correction under hemodynamic monitoring followed by valve replacement or preoperative balloon aortic …


Single Dual-Specific Anti-Pd-L1/Tgf-Β Antibody Synergizes With Chemotherapy As Neoadjuvant Treatment For Pancreatic Ductal Adenocarcinoma: A Preclinical Experimental Study, Haoxiang Zhang, Jiaoshun Chen, Jianwei Bai, Jing Zhang, Shaoyi Huang, Liang Zeng, Pengfei Zhou, Qiang Shen, Tao Yin Mar 2024

Single Dual-Specific Anti-Pd-L1/Tgf-Β Antibody Synergizes With Chemotherapy As Neoadjuvant Treatment For Pancreatic Ductal Adenocarcinoma: A Preclinical Experimental Study, Haoxiang Zhang, Jiaoshun Chen, Jianwei Bai, Jing Zhang, Shaoyi Huang, Liang Zeng, Pengfei Zhou, Qiang Shen, Tao Yin

School of Medicine Faculty Publications

AIMS: Chemotherapy resistance is an important cause of neoadjuvant therapy failure in pancreatic ductal adenocarcinoma (PDAC). BiTP is a single antibody that can simultaneously and dually target transforming growth factor-beta (TGF-β) and programmed cell death 1 ligand 1 (PD-L1). We attempted in this study to investigate the efficacy of BiTP in combination with first-line chemotherapy in PDAC. METHODS: Preclinical assessments of BiTP plus gemcitabine and nab-paclitaxel were completed through a resectable KPC mouse model (C57BL/6J). Spectral flow cytometry, tissue section staining, enzyme-linked immunosorbent assays, Counting Kit-8, transwell, and Western blot assays were used to investigate the synergistic effects. RESULTS: BiTP …


A Comparative Review Of Typical And Atypical Optic Neuritis: Advancements In Treatments, Diagnostics, And Prognosis, Noah J. Spillers, Patrick M. Luther, Norris C. Talbot, Evan J. Kidder, Connor A. Doyle, Salim C. Lutfallah, Alyssa G. Derouen, Sridhar Tirumala, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye, Giustino Varrassi Mar 2024

A Comparative Review Of Typical And Atypical Optic Neuritis: Advancements In Treatments, Diagnostics, And Prognosis, Noah J. Spillers, Patrick M. Luther, Norris C. Talbot, Evan J. Kidder, Connor A. Doyle, Salim C. Lutfallah, Alyssa G. Derouen, Sridhar Tirumala, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye, Giustino Varrassi

School of Medicine Faculty Publications

Optic neuritis (ON) is a debilitating condition that through various mechanisms, including inflammation or demyelination of the optic nerve, can result in partial or total permanent vision loss if left untreated. Accurate diagnosis and promptly initiated treatment are imperative related to the potential of permanent loss of vision if left untreated, which can lead to a significant reduction in the quality of life in affected patients. ON is subtyped as "typical" or "atypical" based on underlying causative etiology. The etiology of ON can be differentiated when appropriate diagnostic testing is performed. Using history taking, neuroimaging, and visual testing to localize …


Acute And Chronic Central Nervous System Oxidative Stress/Toxicity During Hyperbaric Oxygen Treatment Of Subacute And Chronic Neurological Conditions, Paul G. Harch, Stacey Rhodes Mar 2024

Acute And Chronic Central Nervous System Oxidative Stress/Toxicity During Hyperbaric Oxygen Treatment Of Subacute And Chronic Neurological Conditions, Paul G. Harch, Stacey Rhodes

School of Medicine Faculty Publications

INTRODUCTION: Oxygen toxicity has been defined as acute central nervous system (CNS), acute pulmonary, and chronic pulmonary oxygen toxicity. This study identifies acute and chronic CNS oxygen toxicity under 2.0 atmospheres absolute (ATA) pressure of oxygen. Methods: The authors' medical records from September 29, 1989 to January 20, 2023 and correspondence to the authors (9/1994 to 1/20.2023) from patients with signs and/or symptoms historically identified as acute CNS oxygen toxicity and those with neurological deterioration receiving hyperbaric oxygen for neurological conditions were reviewed. Acute cases were those occurring with ≤ 5 HBOTs and chronic cases > 5 HBOTs. Chronic cases were …


Advancing Treatment In Atopic Dermatitis: A Comprehensive Review Of Clinical Efficacy, Safety, And Comparative Insights Into Corticosteroids, Calcineurin Inhibitors, And Phosphodiesterase-4 Inhibitors As Topical Therapies, Tyler D. Hernandez, Sarah J. Aleman, Maria Bao-Loc-Trung, Michael V. Forte, William Brandt, Catherine Armstrong, Jeffrey Howard, Chizoba N. Mosieri, Shahab Ahmadzadeh, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye Mar 2024

Advancing Treatment In Atopic Dermatitis: A Comprehensive Review Of Clinical Efficacy, Safety, And Comparative Insights Into Corticosteroids, Calcineurin Inhibitors, And Phosphodiesterase-4 Inhibitors As Topical Therapies, Tyler D. Hernandez, Sarah J. Aleman, Maria Bao-Loc-Trung, Michael V. Forte, William Brandt, Catherine Armstrong, Jeffrey Howard, Chizoba N. Mosieri, Shahab Ahmadzadeh, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Atopic dermatitis (AD) is a pervasive and multifaceted dermatological disorder causing daily distress to afflicted individuals worldwide. This comprehensive review synthesizes the historical and contemporary advancements in therapeutic strategies, offering a critical analysis of their efficacy, safety profiles, and adaptability. The enduring role of topical corticosteroids in managing AD is examined, acknowledging their potent anti-inflammatory properties alongside their potential adverse side effects, particularly in extended usage. The article explores the utilization of topical calcineurin inhibitors like tacrolimus and pimecrolimus, highlighting their novel anti-inflammatory pathways while also scrutinizing concerns over potential malignancies that relegate them to second-line therapy. The present investigation …


Pancreatic Cancer Tumor Microenvironment Is A Major Therapeutic Barrier And Target, Conner Hartupee, Bolni Marius Nagalo, Chiswili Y. Chabu, Mulu Z. Tesfay, Joycelynn Coleman-Barnett, John T. West, Omeed Moaven Feb 2024

Pancreatic Cancer Tumor Microenvironment Is A Major Therapeutic Barrier And Target, Conner Hartupee, Bolni Marius Nagalo, Chiswili Y. Chabu, Mulu Z. Tesfay, Joycelynn Coleman-Barnett, John T. West, Omeed Moaven

School of Medicine Faculty Publications

Pancreatic Ductal Adenocarcinoma (PDAC) is projected to become the 2nd leading cause of cancer-related deaths in the United States. Limitations in early detection and treatment barriers contribute to the lack of substantial success in the treatment of this challenging-to-treat malignancy. Desmoplasia is the hallmark of PDAC microenvironment that creates a physical and immunologic barrier. Stromal support cells and immunomodulatory cells face aberrant signaling by pancreatic cancer cells that shifts the complex balance of proper repair mechanisms into a state of dysregulation. The product of this dysregulation is the desmoplastic environment that encases the malignant cells leading to a dense, hypoxic …