Digital Commons Network^™

Adverse Events Of Immune Checkpoint Therapy Alone Versus When Combined With Vascular Endothelial Growth Factor Inhibitors: A Pooled Meta-Analysis Of 1735 Patients, Iuliia Kovalenko, Wern Lynn Ng, Yimin Geng, Yinghong Wang, Pavlos Msaouel, Petros Grivas, Omar Alhalabi

Faculty, Staff and Student Publications

Background: Combining immune checkpoint therapy (ICT) and vascular endothelial growth factor inhibitors (VEGFi) may result in increased treatment-related and immune-related adverse events (TRAEs and irAEs) compared to ICT alone. This metanalysis was conducted to identify prospective phase II or III clinical studies that evaluated the toxicity profile of ICT + VEGFi compared to ICT alone.

Methods: A systematic search was performed across all cancer types and major databases until August 10, 2022, and screening was done by two independent investigators. Inclusion criteria included phase 2 or 3 studies with at least one arm of patients treated with combination therapy and …

Blockade Of Mglur5 In Astrocytes Derived From Human Ipscs Modulates Astrocytic Function And Increases Phagocytosis, Izabella B Q De Lima, Pablo L Cardozo, Julia S Fahel, Juliana P S Lacerda, Aline S Miranda, Fabiola M Ribeiro

Faculty, Staff and Student Publications

TNF-α is essential for induction and maintenance of inflammatory responses and its dysregulation is associated with susceptibility to various pathogens that infect the central nervous system. Activation of both microglia and astrocytes leads to TNF-α production, which in turn triggers further activation of these cells. Astrocytes have been implicated in the pathophysiology of a wide range of neurodegenerative diseases with either harmful or protective roles, as these cells are capable of secreting several inflammatory factors and also promote synapse elimination and remodeling. These responses are possible because they sense their surroundings via several receptors, including the metabotropic glutamate receptor 5 …

Predictive Modeling Using Shape Statistics For Interpretable And Robust Quality Assurance Of Automated Contours In Radiation Treatment Planning, Zachary T Wooten, Cenji Yu, Laurence E Court, Christine B Peterson

Faculty, Staff and Student Publications

Deep learning methods for image segmentation and contouring are gaining prominence as an automated approach for delineating anatomical structures in medical images during radiation treatment planning. These contours are used to guide radiotherapy treatment planning, so it is important that contouring errors are flagged before they are used for planning. This creates a need for effective quality assurance methods to enable the clinical use of automated contours in radiotherapy. We propose a novel method for contour quality assurance that requires only shape features, making it independent of the platform used to obtain the images. Our method uses a random forest …

Super-Resolution And Segmentation Deep Learning For Breast Cancer Histopathology Image Analysis, Aniwat Juhong, Bo Li, Cheng-You Yao, Chia-Wei Yang, Dalen W Agnew, Xuefei Huang, Zhen Qiu

Faculty, Staff and Student Publications

Traditionally, a high-performance microscope with a large numerical aperture is required to acquire high-resolution images. However, the images' size is typically tremendous. Therefore, they are not conveniently managed and transferred across a computer network or stored in a limited computer storage system. As a result, image compression is commonly used to reduce image size resulting in poor image resolution. Here, we demonstrate custom convolution neural networks (CNNs) for both super-resolution image enhancement from low-resolution images and characterization of both cells and nuclei from hematoxylin and eosin (H&E) stained breast cancer histopathological images by using a combination of generator and discriminator …

Evaluation Of Scrub Typhus Surveillance, Alwar District, Rajasthan, India, July-August 2020, Surendra M Prajapati, Kanica Kaushal, Simmi Tiwari, Ajit Shewale, Tushar Nale

Faculty, Staff and Student Publications

INTRODUCTION: Scrub typhus is one of the most underreported and fatal illnesses accounting for 23% of all febrile illness. Rajasthan reported cases during 2018-2019 in state reporting system but did not report any case to central Integrated Disease Surveillance Programme (IDSP) unit. We evaluated the Scrub typhus surveillance system in Alwar district, Rajasthan, with the objective of describing and evaluating the system and providing evidence-based recommendations to identify gaps.

MATERIAL AND METHODS: In cross-sectional study, we reviewed records and conducted key informant interviews at district- and block-level health facilities. Using US Centers for Disease Control guidelines, we evaluated the system …

Corrigendum: Semnet: Learning Semantic Attributes For Human Activity Recognition With Deep Belief Networks, Shanmuga Venkatachalam, Harideep Nair, Ming Zeng, Cathy Shunwen Tan, Ole J Mengshoel

Faculty, Staff and Student Publications

This corrects the article "SemNet: Learning semantic attributes for human activity recognition with deep belief networks" in volume 5, 879389.

PMID: 36968617

Anti-Inflammatory Effects Of Vagus Nerve Stimulation In Pediatric Patients With Epilepsy, Supender Kaur, Nathan R Selden, Alejandro Aballay

Faculty, Staff and Student Publications

INTRODUCTION: The neural control of the immune system by the nervous system is critical to maintaining immune homeostasis, whose disruption may be an underlying cause of several diseases, including cancer, multiple sclerosis, rheumatoid arthritis, and Alzheimer's disease.

METHODS: Here we studied the role of vagus nerve stimulation (VNS) on gene expression in peripheral blood mononuclear cells (PBMCs). Vagus nerve stimulation is widely used as an alternative treatment for drug-resistant epilepsy. Thus, we studied the impact that VNS treatment has on PBMCs isolated from a cohort of existing patients with medically refractory epilepsy. A comparison of genome-wide changes in gene expression …

Phase 1/2 Study Of Epacadostat In Combination With Durvalumab In Patients With Metastatic Solid Tumors, Aung Naing, Alain P Algazi, Gerald S Falchook, Benjamin C Creelan, John Powderly, Minal Barve, Pierre L Triozzi, John Hamm, Gongfu Zhou, Chris Walker, Zhiwan Dong, Manish R Patel

Faculty, Staff and Student Publications

Background: Targeting programmed cell death protein 1 (PD-1) and indoleamine 2,3-dioxygenase (IDO1) pathways is an appealing option for cancer treatment.

Methods: The open-label, phase 1/2 ECHO-203 study evaluated the safety, tolerability, and efficacy of the IDO1 inhibitor epacadostat in combination with durvalumab, a human anti-PD-L1 monoclonal antibody in adult patients with advanced solid tumors.

Results: The most common treatment-related adverse events were fatigue (30.7%), nausea (21.0%), decreased appetite (13.1%), pruritus (12.5%), maculopapular rash (10.8%), and diarrhea (10.2%). Objective response rate (ORR) in the overall phase 2 population was 12.0%. Higher ORR was observed in immune checkpoint inhibitor (CPI)-naïve patients (16.1%) …

Survival Outcomes Used To Validate Version 9 Of The American Joint Committee On Cancer Staging System For Appendiceal Cancer, Lauren M Janczewski, Amanda E Browner, Joseph H Cotler, Heidi Nelson, Sanjay Kakar, Nader N Hanna, Richard M Goldberg, M Kay Washington, Elliot A Asare, Michael J Overman, American Joint Committee On Cancer Expert Panel On Cancers For The Lower Gastrointestinal Appendix Disease Site

Faculty, Staff and Student Publications

The standard for cancer staging in the United States for all cancer sites, including primary carcinomas of the appendix, is the American Joint Committee on Cancer (AJCC) staging system. AJCC staging criteria undergo periodic revisions, led by a panel of site-specific experts, to maintain contemporary staging definitions through the evaluation of new evidence. Since its last revision, the AJCC has restructured its processes to include prospectively collected data because large data sets have become increasingly robust and available over time. Thus survival analyses using AJCC eighth edition staging criteria were used to inform stage group revisions in the version 9 …

Severe Radiation-Induced Lymphopenia During Concurrent Chemoradiotherapy For Stage Iii Non-Small Cell Lung Cancer: External Validation Of Two Prediction Models, Peter S N Van Rossum, Celia Juan-Cruz, Barbara Stam, Maddalena M G Rossi, Steven H Lin, José S A Belderbos

Faculty, Staff and Student Publications

BACKGROUND: Severe radiation-induced lymphopenia (RIL) in patients undergoing chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC) is associated with decreased immunotherapy efficacy and survival. At The Christie and MD Anderson Cancer Center (MDACC), prediction models for lymphopenia were developed in lung and esophageal cancer patients, respectively. The aim of this study was to externally validate both models in patients with stage III NSCLC.

METHODS: Patients who underwent concurrent CRT for stage III NSCLC in 2019-2021 were studied. Outcomes were grade ≥3 and grade 4 lymphopenia during CRT. The Christie model predictors for grade ≥3 lymphopenia included age, baseline lymphocyte count, …

Immune Checkpoint Inhibitors In Advanced Cutaneous Squamous Cell Carcinoma: A Systemic Review And Meta-Analysis, Haoran Zhang, Ai Zhong, Junjie Chen

Faculty, Staff and Student Publications

BACKGROUND: To evaluate the immune checkpoint inhibitors (CPI) for the treatment of patients with advanced cutaneous squamous cell carcinoma (CSCC).

MATERIALS AND METHODS: A meta-analysis was conducted, and the efficacy and safety of CPI were assessed.

RESULTS: A total of 13 studies with 980 patients were included. The pooled objective response rate (ORR) and disease control rate were 47.2% and 64.4%, separately. In addition, patients with primary tumor located in head and neck (odds ratio [OR]: 0.374, 95% confidence interval [CI]: 0.219-0.640, p < 0.001) and positive expression of programmed death ligand 1 (OR: 0.364, 95% CI: 0.158-0.842, P = 0.018) had superior ORR during CPI treatment. The incidence of progression free survival at 6 and 12 months was 59.3% and 52.8%, and 80.6% and 76.4% for overall survival. As for safety, the overall incidence of adverse events with all grades and 3-4 grade was 76.9% and 20.2%.

CONCLUSIONS: Our systematic review confirmed the satisfying efficacy and acceptable toxicity of CPI for advanced CSCC.

Distinct Patterns Of Auto-Reactive Antibodies Associated With Organ-Specific Immune-Related Adverse Events, Mehmet Altan, Quan-Zhen Li, Qi Wang, Natalie I Vokes, Ajay Sheshadri, Chengsong Zhu, Saumil Gandhi, Mara B Antonoff, Stephen Swisher, Jing Wang, Lauren A Byers, Noha Abdel-Wahab, Maria C Franco-Vega, Yinghong Wang, J Jack Lee, Jianjun Zhang, John V Heymach

Faculty, Staff and Student Publications

UNLABELLED: The roles of preexisting auto-reactive antibodies in immune-related adverse events (irAEs) associated with immune checkpoint inhibitor therapy are not well defined. Here, we analyzed plasma samples longitudinally collected at predefined time points and at the time of irAEs from 58 patients with immunotherapy naïve metastatic non-small cell lung cancer treated on clinical protocol with ipilimumab and nivolumab. We used a proteomic microarray system capable of assaying antibody reactivity for IgG and IgM fractions against 120 antigens for systemically evaluating the correlations between auto-reactive antibodies and certain organ-specific irAEs. We found that distinct patterns of auto-reactive antibodies at baseline were …

Case Report: Responses To The Combination Of Gemcitabine With Sirolimus In Two Patients With Tsc-Mutated Sarcomas, Elise F Nassif, Cissimol P Joseph, Rossana Lazcano, Jocelyn T Joseph, Prapassorn Thirasastr, Neeta Somaiah

Faculty, Staff and Student Publications

TSC-mutated sarcomas are rare molecular and histologic types of sarcoma. Due to the presence of their specific oncogenic driver mutation, these sarcomas are particularly sensitive to mTOR inhibitors. Recently, nab-sirolimus, an albumin-bound mTOR inhibitor, was approved by the Food and Drug Administration (FDA) for PEComas, which harbor a TSC mutation, and this drug remains the only FDA-approved systemic treatment for these tumors. We report on two cases of patients with TSC-mutated sarcomas who experienced significant responses to the combination of gemcitabine and sirolimus, after progression on prior gemcitabine-based chemotherapy and single agent mTOR inhibition with nab-sirolimus. …

Formulaicity And Contexts: A Multimodal Analysis Of The Japanese Utterance-Final Tteyuu, Michiko Kaneyasu

World Languages and Cultures Faculty Publications

This study investigates the use of the utterance-final tteyuu [ʔtejɯː], a combination of the quotative particle tte and the verb yuu (‘say’). Although its lexicalized status and utterance-final occurrence are commonly observed, we still know little about its real-time functions. The analysis of 120 examples in varied contexts shows its general usage to clarify something expressed in the prior talk, which is a type of repair practice. More importantly, the analysis reveals how the participants’ understanding of the ongoing speech activity and multimodal cues affect its use and interpretation. Furthermore, some specialized usages appear to motivate activity-bound pragmatic inferencing, leading …

(Transforme Des Mines De Plomb En Or): Webster Et L'Alchimie Du Nous (En Rap), Peter Schulman

World Languages and Cultures Faculty Publications

[Introduction] Auteur de plusieurs disques et de nombreux ateliers d'écriture internationaux, d'un livre pour enfants et d'une d'exposition sur des escclaves fugitifs au Musée national des beaux-arts du Québec¹, le rappeur <> Webster (de son vrai nom Aly Ndiaye) est connu pour la profondeur de ses chansons, nourries d'Histoire (fidèle à sa formation d'historien), mais surtout d'un humanisme qui fait face non seulement aux attitudes racistes qu'il a dû affronter pendant sa jeunesse, et aussi à l'isolement créé par des barrières artificielles imposées par la société québecoise dont il fait partie.

A Theory Of The Covid-19 Pandemic’S Impact On The Government-Citizen Relationship / Teorija Vpliva Pandemije Covid-19 Na Odnos Med Vlado In Državljani, Lewis Luartz

Political Science Faculty Articles and Research

This paper explores how crises, such as the COVID- 19 pandemic, can impact political behavior amid restrictions. Specifically, this paper builds a theoretical model suggesting the pandemic promoted restriction-oriented policies from the government in response to the crisis while promoting populist tendencies among citizens who disagree with those policies. Moreover, through a formal two-player extensive form game, the model promoted in this paper suggests restrictions are unpopular enough that citizens may push back on such policies regardless of crisis severity. The theoretical outcomes here have significant implications on governance, given that politicians care about re-election.

A Prophylactic Approach To Compact Constitutionality, Katherine Mims Crocker

Faculty Publications

From COVID-19 to climate change, immigration to health insurance, firearms control to electoral reform: state politicians have sought to address all these hot-button issues by joining forces with other states. The U.S. Constitution, however, forbids states to “enter into any Agreement or Compact” with each other “without the Consent of Congress,” a requirement that proponents of much interstate action, especially around controversial topics, would hope to circumvent.

The Supreme Court lets them do just that. By interpreting “any Agreement or Compact” so narrowly that it is difficult to see what besides otherwise unlawful coordination qualifies, the Court has essentially read …

Prevalence Of Depressive Symptoms And Correlates Among Individuals Who Self-Reported Sars-Cov-2 Infection After Optimizing The Covid-19 Response In China, Jinfeng He, Ping Cen, Mu Li, Tong Luo, Rongjing Zhang, Shanmei Zhong, Cai Qin, Zeyu Li, Yuan Yang, Huiqi Pan, Mengdi Zhao, Xiaoqiong Wu, Junjun Jiang, Hao Liang, Li Ye, Bingyu Liang

Faculty, Staff and Student Publications

BACKGROUND: The burden of depression symptoms has increased among individuals infected with SARS-CoV-2 during COVID-19 pandemic. However, the prevalence and associated factors of depressive symptoms among individuals infected with SARS-CoV-2 remain uncertain after optimizing the COVID-19 response in China.

METHODS: An online cross-sectional survey was conducted among the public from January 6 to 30, 2023, using a convenience sampling method. Sociodemographic and COVID-19 pandemic-related factors were collected. The depression symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Logistic regression analysis was performed to explore the associated factors with depressive symptoms.

RESULTS: A total of 2,726 participants completed the survey. …

Fecal Microbiota Transplantation In Parkinson’S Disease-A Randomized Repeat-Dose, Placebo-Controlled Clinical Pilot Study, Heather T Essigmann, Netanya S Utay, Michael Newmark, Mya C Schiess

Faculty, Staff and Student Publications

BACKGROUND AND PURPOSE: The intestinal microbiome plays a primary role in the pathogenesis of neurodegenerative disorders and may provide an opportunity for disease modification. We performed a pilot clinical study looking at the safety of fecal microbiota transplantation (FMT), its effect on the microbiome, and improvement of symptoms in Parkinson's disease.

METHODS: This was a randomized, double-blind placebo-controlled pilot study, wherein orally administered lyophilized FMT product or matching placebo was given to 12 subjects with mild to moderate Parkinson's disease with constipation twice weekly for 12 weeks. Subjects were followed for safety and clinical improvement for 9 additional months (total …

The Gastrointestinal-Brain-Microbiota Axis: A Promising Therapeutic Target For Ischemic Stroke, Jian-Zhuang Li

Faculty, Staff and Student Publications

Ischemic stroke is a highly complex systemic disease characterized by intricate interactions between the brain and gastrointestinal tract. While our current understanding of these interactions primarily stems from experimental models, their relevance to human stroke outcomes is of considerable interest. After stroke, bidirectional communication between the brain and gastrointestinal tract initiates changes in the gastrointestinal microenvironment. These changes involve the activation of gastrointestinal immunity, disruption of the gastrointestinal barrier, and alterations in gastrointestinal microbiota. Importantly, experimental evidence suggests that these alterations facilitate the migration of gastrointestinal immune cells and cytokines across the damaged blood-brain barrier, ultimately infiltrating the ischemic brain. …

Childhood Acute Poisoning At Haiphong Children's Hospital: A 10-Year Retrospective Study

Faculty, Staff and Student Publications

INTRODUCTION: Children are most often harmed by acute poisoning, which may cause disability or even death. This demonstrates the critical necessity for epidemiologic studies specific to each nation and area since they aid in developing plans for the prevention of acute poisoning. There are no data or outdated data on acute poisoning in children in Vietnam. This research would partly fill this existing gap and compare the trend with other places across the globe.

METHODS: A retrospective study was conducted in the 10-year period from 2012 to 2021 in Haiphong Children's Hospital, Vietnam.

RESULTS: There were 771 children hospitalized due …

One Patient With 4 Different Primary Cancers: A Case Report

Faculty, Staff and Student Publications

BACKGROUND: The development of medicine, especially in oncology, has been helping prolong the cancer patients' survival, but also leads to increasing the possibility of getting multiple cancers. However, the possibility of getting 4 primary cancers in 4 different sites is extremely rare.

CASE PRESENTATION: A 63-year-old female patient was diagnosed with thyroid cancer in 2018, and then with right colon cancer in 2019. In 2020, this patient was diagnosed with left renal pelvis cancer, and most recently, in April 2022, she was hospitalized with bladder cancer diagnosis. Thanks to being closely and regularly followed-up, her malignancies had been detected early …

Review: Discogenic Back Pain: Update On Treatment, Anh Phung, Jamal Hasoon, Thomas Simopoulos, Cyrus Yazdi, Christopher L Robinson

Faculty, Staff and Student Publications

Purpose of review: Lower back pain (LBP) has a lifetime prevalence of 80% in the United States population. Discogenic back pain (DBP), a subcategory of LBP, occurs as a result of the interverbal disc degeneration without disc herniation. Diagnosis relies on history, physical exam, and imaging such as MRI, provocative discography, or CT discography.

Recent findings: Treatment of DBP involves a multifaceted approach with an emphasis on conservative measures including behavioral modification, pharmacologic management, and other non-pharmacologic interventions with invasive therapy reserved for select patients. Due to the paucity of data on the treatment of DBP, treatment also relies on …

Sulforaphane Improves Cognitive Function Administered Following Traumatic Brain Injury

Faculty, Staff and Student Publications

As the second leading cause of death among Americans aged 10 to 34, suicide is a serious public health concern. One potential predictor of suicidality is dating violence (DV) victimization, such as any physical, psychological, or sexual abuse by a current or former intimate partner. However, little longitudinal data exists on the relationship between suicidal ideation and DV. To address this gap in knowledge, we leverage data from two years of our longitudinal study

Pharmacokinetics And Pharmacodynamics Of Intranasal And Intramuscular Administration Of Naloxone In Working Dogs Administered Fentanyl, Kenneth J Drobatz, Amanda Mcguire, Cynthia M Otto

Faculty, Staff and Student Publications

BACKGROUND: Working dogs exposed to narcotics might require reversal in the field.

OBJECTIVE: To explore the pharmacokinetic and pharmacodynamic effects of naloxone administered intramuscularly (IM) or intranasally (IN) to reverse fentanyl sedation in working dogs.

ANIMALS: Ten healthy, working dogs aged 1.7 ± 1 year and weighing 26 ± 3 kg.

METHODS: In this randomized, controlled cross-over study dogs received either 4 mg of naloxone IN or IM 10 minutes after fentanyl (0.3 mg IV) administration. Sedation was assessed at baseline and 5 minutes after fentanyl administration, then at 5, 10, 15, 20, 25, 30, 60 and 120 minutes after …

Development And Internal Validation Of A Novel Nomogram For Predicting Lymph Node Invasion For Prostate Cancer Patients Undergoing Extended Pelvic Lymph Node Dissection, Zeshen Wu, Jianwei Wu, Yulu Peng, Yonghong Li, Fangjian Zhou

Faculty, Staff and Student Publications

BACKGROUND: Few studies have focused on the performance of Briganti 2012, Briganti 2017 and MSKCC nomograms in the Chinese population in assessing the risk of lymph node invasion(LNI) in prostate cancer(PCa) patients and identifying patients suitable for extended pelvic lymph node dissection(ePLND). We aimed to develop and validate a novel nomogram based on Chinese PCa patients treated with radical prostatectomy(RP) and ePLND for predicting LNI.

METHODS: We retrospectively retrieved clinical data of 631 patients with localized PCa receiving RP and ePLND at a Chinese single tertiary referral center. All patients had detailed biopsy information from experienced uropathologist. Multivariate logistic-regression analyses …

“So Many Extra Safety Layers:” Virtual Service Provision And Implementing Social Distancing In Interpersonal Violence Service Agencies During Covid-19, Leila Wood

Faculty, Staff and Student Publications

The coronavirus pandemic necessitated rapid shifts in approach for service providers working with survivors of interpersonal violence. To reduce the spread of the virus, providers and agencies implemented a rapid and unplanned expansion of virtual services while also developing new protocols to support safe and socially distant in-person services. To understand how these shifts have impacted victim service professionals and the survivors they serve, to provide guidance for on-going efforts, and to inform planning for future public health emergencies, this study asks the question: What approaches did the interpersonal violence workforce use to address social distancing needs during COVID-19? Semi-structured …

Hyperviscosity Syndrome Induced Bilateral Visual And Auditory Impairment In Therapy Resistant Waldenström Macroglobulinemia With Myd88 And Cxcr4 Mutations, Kirk Bourgeois

Faculty, Staff and Student Publications

Hyperviscosity syndrome (HVS) is an emergent complication of Waldenström macroglobulinemia (WM) characterized by visual, neurologic, and rarely auditory impairment. We report a 69-year-old female with MYD88 and CXCR4-mutant WM who developed HVS resulting in bilateral blindness and deafness associated with neurologic manifestations including confusion, severe generalized weakness, and imbalance. Ophthalmologic evaluation revealed bilateral central retinal vein occlusion (CRVO), diffuse retinal hemorrhages, macular edema, and serous macular detachments (SMD). Magnetic resonance imaging of the brain showed bleeding in the inner ears. Management was challenging as her WM was resistant to systemic therapies including bendamustine + rituximab (BR) and rituximab + bortezomib …

Community Socioeconomic And Urban-Rural Differences In Emergency Medical Services Times For Suspected Stroke In North Carolina, Jane H Brice

Faculty, Staff and Student Publications

OBJECTIVE: Our objectives were to describe time intervals of EMS encounters for suspected stroke patients in North Carolina (NC) and evaluate differences in EMS time intervals by community socioeconomic status (SES) and rurality.

METHODS: This cross-sectional study used statewide data on EMS encounters of suspected stroke in NC in 2019. Eligible patients were adults requiring EMS transport to a hospital following a 9-1-1 call for stroke-like symptoms. Incident street addresses were geocoded to census tracts and linked to American Community Survey SES data and to rural-urban commuting area (RUCA) codes. Community SES was defined as high, medium, or low based …

Il-33 Mediates Pseudomonas Induced Airway Fibrogenesis And Is Associated With Clad, Jon Finan, Archit Kumar, Daniel E Rinewalt, Hilary J Goldberg, Ann Woolley, Hari Reddy Mallidi, Gary Visner, Amit Gaggar, Kapil N Patel, Nirmal S Sharma

Faculty, Staff and Student Publications

BACKGROUND: Long term outcomes of lung transplantation are impacted by the occurrence of chronic lung allograft dysfunction (CLAD). Recent evidence suggests a role for the lung microbiome in the occurrence of CLAD, but the exact mechanisms are not well defined. We hypothesize that the lung microbiome inhibits epithelial autophagic clearance of pro-fibrotic proteins in an IL-33 dependent manner, thereby augmenting fibrogenesis and risk for CLAD.

METHODS: Autopsy derived CLAD and non-CLAD lungs were collected. IL-33, P62 and LC3 immunofluorescence was performed and assessed using confocal microscopy. Pseudomonas aeruginosa (PsA), Streptococcus Pneumoniae (SP), Prevotella Melaninogenica (PM), recombinant IL-33 or PsA-lipopolysaccharide was …