Critical Care Commons^™

Cd73-Dependent Adenosine Signaling Through Adora2b Drives Immunosuppression In Ductal Pancreatic Cancer, Erika Y Faraoni, Kanchan Singh, Vidhi Chandra, Olivereen Le Roux, Yulin Dai, Ismet Sahin, Baylee J O'Brien, Lincoln N Strickland, Le Li, Emily Vucic, Amanda N Warner, Melissa Pruski, Trent Clark, George Van Buren, Nirav C Thosani, John S Bynon, Curtis J Wray, Dafna Bar-Sagi, Kyle L Poulsen, Lana A Vornik, Michelle I Savage, Shizuko Sei, Altaf Mohammed, Zhongming Zhao, Powel H Brown, Tingting Mills, Holger K Eltzschig, Florencia Mcallister, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

The microenvironment that surrounds pancreatic ductal adenocarcinoma (PDAC) is profoundly desmoplastic and immunosuppressive. Understanding triggers of immunosuppression during the process of pancreatic tumorigenesis would aid in establishing targets for effective prevention and therapy. Here, we interrogated differential molecular mechanisms dependent on cell of origin and subtype that promote immunosuppression during PDAC initiation and in established tumors. Transcriptomic analysis of cell-of-origin-dependent epithelial gene signatures revealed that Nt5e/CD73, a cell-surface enzyme required for extracellular adenosine generation, is one of the top 10% of genes overexpressed in murine tumors arising from the ductal pancreatic epithelium as opposed to those rising from acinar cells. …

Acoustic Voice And Speech Biomarkers Of Treatment Status During Hospitalization For Acute Decompensated Heart Failure, Olivia M Murton, G William Dec, Robert E Hillman, Maulik D Majmudar, Johannes Steiner, John V Guttag, Daryush D Mehta

Faculty, Staff and Student Publications

This study investigates acoustic voice and speech features as biomarkers for acute decompensated heart failure (ADHF), a serious escalation of heart failure symptoms including breathlessness and fatigue. ADHF-related systemic fluid accumulation in the lungs and laryngeal tissues is hypothesized to affect phonation and respiration for speech. A set of daily spoken recordings from 52 patients undergoing inpatient ADHF treatment was analyzed to identify voice and speech biomarkers for ADHF and to examine the trajectory of biomarkers during treatment. Results indicated that speakers produce more stable phonation, a more creaky voice, faster speech rates, and longer phrases after ADHF treatment compared …

Assessment Of Opioid-Induced Immunomodulation In Experimental And Clinical Sepsis, Brittany Dawn Bissell, Jamie L. Sturgill, Maria E. C. Bruno, Erick D. Lewis, Marlene E. Starr

Markey Cancer Center Faculty Publications

CONTEXT: Opioids remain a standard supportive therapy in patients admitted to the ICU with sepsis. However, as preclinical models indicate an association between opioid exposure and immunosuppression, the use of this class of drugs warrants investigation. The objective of this study was to investigate whether opioid exposure causes immunosuppression in patients with sepsis, and to use a murine sepsis model to determine the effects of opioid exposure on secondary infection.

HYPOTHESIS: We hypothesized opioid exposure would be associated with immunosuppression in patients with sepsis and secondary infection in a murine sepsis model.

METHODS AND MODELS: This was a two-phase preclinical …

The Rising Tide Of Revisional Surgery: Tracking Changes In Index Cases Among Bariatric-Accredited Fellowships, Lincoln N Strickland, Erika Y Faraoni, Wei Ruan, Xiaoyi Yuan, Holger K Eltzschig, Jennifer M Bailey-Lundberg

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense desmoplastic stroma that impedes drug delivery, reduces parenchymal blood flow, and suppresses the anti-tumor immune response. The extracellular matrix and abundance of stromal cells result in severe hypoxia within the tumor microenvironment (TME), and emerging publications evaluating PDAC tumorigenesis have shown the adenosine signaling pathway promotes an immunosuppressive TME and contributes to the overall low survival rate. Hypoxia increases many elements of the adenosine signaling pathway, resulting in higher adenosine levels in the TME, further contributing to immune suppression. Extracellular adenosine signals through 4 adenosine receptors (Adora1, Adora2a, Adora2b, Adora3). Of …

Cytological Diagnosis Of Pilomatrixoma And Its Diagnostic Pitfalls, Sabina Khan, Inara Abeer, Musharraf Husain, Sujata Jetley

Faculty, Staff and Student Publications

BACKGROUND: Pilomatrixoma (PMX) is a relatively uncommon benign cutaneous neoplasm arising from skin adnexa. It presents as a subcutaneous asymptomatic nodule mostly in the head and neck region and is frequently misdiagnosed by the clinicians. Although easily diagnosed on histopathology, the cytologic features of PMX are less distinctive, depending on the stage and evolution of disease and may mimic other benign or even malignant lesions.

AIM: To study the cyto-morphological features of this uncommon neoplasm and identify its potential diagnostic pitfalls on fine needle aspiration cytology (FNAC).

MATERIAL AND METHODS: Archival records of histopathologically diagnosed Pilomatrixoma were analyzed during study …

Financial Toxicity In Cancer Patients And Subsequent Risk Of Repeat Acute Care Utilization, Julia J Shi, J Alberto Maldonado, Chi-Fang Wu, Susan K Peterson, Ying-Shiuan Chen, Kevin Diao, Robert J Volk, Sharon H Giordano, Ya-Chen T Shih, Kelsey Kaiser, Grace L Smith

Faculty, Staff and Student Publications

BACKGROUND: Acute care (AC) visits by cancer patients are costly sources of healthcare resources and can exert a financial burden of oncology care both for individuals with cancer and healthcare systems. We sought to identify whether cancer patients who reported more severe initial financial toxicity (FT) burdens shouldered excess risks for acute care utilization.

METHODS: In 225 adult patients who participated in the Economic Strain and Resilience in Cancer (ENRICh) survey study of individuals receiving ambulatory cancer care between March and September 2019, we measured the baseline FT (a multidimensional score of 0-10 indicating the least to most severe global, …

A Unified Model Of Age-Related Cardiovascular Disease, Michael Fossel, Joe Bean, Nina Khera, Mikhail G Kolonin

Faculty, Staff and Student Publications

Despite progress in biomedical technologies, cardiovascular disease remains the main cause of mortality. This is at least in part because current clinical interventions do not adequately take into account aging as a driver and are hence aimed at suboptimal targets. To achieve progress, consideration needs to be given to the role of cell aging in disease pathogenesis. We propose a model unifying the fundamental processes underlying most age-associated cardiovascular pathologies. According to this model, cell aging, leading to cell senescence, is responsible for tissue changes leading to age-related cardiovascular disease. This process, occurring due to telomerase inactivation and telomere attrition, …

Coronary Artery Calcium Score On Standard Of Care Oncologic Ct Scans For The Prediction Of Adverse Cardiovascular Events In Patients With Non-Small Cell Lung Cancer Treated With Concurrent Chemoradiotherapy, Efstratios Koutroumpakis, Ting Xu, Juan Lopez-Mattei, Tinsu Pan, Yang Lu, Jorge A Irizarry-Caro, Radhe Mohan, Xiaodong Zhang, Qing H Meng, Ruitao Lin, Tianlin Xu, Anita Deswal, Zhongxing Liao

Faculty, Staff and Student Publications

INTRODUCTION: Chemoradiotherapy (CRT) has been associated with increased incidence of cardiovascular (CV) adverse events (CVAE). Coronary artery calcium scoring (CAC) has shown to predict coronary events beyond the traditional CV risk factors. This study examines whether CAC, measured on standard of care, non-contrast chest CT (NCCT) imaging, predicts the development of CVAE in patients with non-small cell lung cancer (NSCLC) treated with CRT.

METHODS: Patients with NSCLC treated with CRT at MD Anderson Cancer Center from 7/2009 until 4/2014 and who had at least one NCCT scan within 6 months from their first CRT were identified. CAC scoring was performed …

Anticancer Effect Of Illicium Verum (Star Anise Fruit) Against Human Breast Cancer Mcf-7 Cell Line, Asra Khan Pahore, Shagufta Khan, Nasim Karim

Department of Biological & Biomedical Sciences

Objective: To investigate the anticancer effect of Illicium verum against human breast cancer MCF-7 cell line.
Methods: An experimental study was conducted in Multidisciplinary and Tissue Culture Laboratory, Aga Khan University in collaboration with Pharmacology Department of Bahria University Medical and Dental College, Karachi, Pakistan from January 2021 to June 2021. MCF-7 cells of Luminal-A breast cancer were seeded in 96-well plate and treated with I.verum methanol extract. After incubation, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) dye was used for cell viability and cell proliferation assays to determine the number of dead and viable cells, and the absorbance was measured using an enzyme-linked …

Simultaneous Onset Of Haematological Malignancy And Covid: An Epicovideha Survey, Chiara Cattaneo, Jon Salmanton-García, Francesco Marchesi, Shaimaa El-Ashwah, Federico Itri, Barbora Weinbergerová, Maria Gomes Da Silva, Michelina Dargenio, Julio Dávila-Valls, Natasha Ali

Department of Pathology and Laboratory Medicine

Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines.
Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022.
Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients …

Polygenic Risk Score Improves The Accuracy Of A Clinical Risk Score For Coronary Artery Disease, Austin King, Lang Wu, Hong-Wen Deng, Hui Shen, Chong Wu

Faculty, Staff and Student Publications

BACKGROUND: The value of polygenic risk scores (PRSs) towards improving guideline-recommended clinical risk models for coronary artery disease (CAD) prediction is controversial. Here we examine whether an integrated polygenic risk score improves the prediction of CAD beyond pooled cohort equations. METHODS: An observation study of 291,305 unrelated White British UK Biobank participants enrolled from 2006 to 2010 was conducted. A case-control sample of 9499 prevalent CAD cases and an equal number of randomly selected controls was used for tuning and integrating of the polygenic risk scores. A separate cohort of 272,307 individuals (with follow-up to 2020) was used to examine …

Chronic Diarrhea: A Rare Presentation Of Hodgkin's Lymphoma, Saira Furqan, Sajjad Ali Khan, Dania Ali, Kaleemullah Badini

Section of Diabetes, Endocrinology and Metabolism

Hodgkin's Lymphoma is a cancer affecting the lymphatic system. There are two subtypes of Hodgkin's Lymphoma: Nodular lymphocyte predominant (NLPHL) and classical Hodgkin's Lymphoma which has further four types. It has a bimodal distribution and is more common among males. The most common presentation is painless swelling in the neck, armpit or groin region. Associated Symptoms include night sweats, unintentional weight loss, fever, persistent cough or dyspnea. Involvement of the gastrointestinal tract is a rare occurrence. Diagnosis is based on hematological, radiological and histochemical studies. Here we report a rare presentation of a 47-year-old male who presented with symptoms of …

Rad Regulation Of Cav12 Channels Controls Cardiac Fight-Or-Flight Response, Arianne Papa, Sergey I Zakharov, Alexander N Katchman, Jared S Kushner, Bi-Xing Chen, Lin Yang, Guoxia Liu, Alejandro Sanchez Jimenez, Robyn J Eisert, Gary A Bradshaw, Wen Dun, Shah R Ali, Aaron Rodriques, Karen Zhou, Veli Topkara, Mu Yang, John P Morrow, Emily J Tsai, Arthur Karlin, Elaine Wan, Marian Kalocsay, Geoffrey S Pitt, Henry M Colecraft, Manu Ben-Johny, Steven O Marx

Faculty, Staff and Student Publications

Fight-or-flight responses involve β-adrenergic-induced increases in heart rate and contractile force. In the present study, we uncover the primary mechanism underlying the heart's innate contractile reserve. We show that four protein kinase A (PKA)-phosphorylated residues in Rad, a calcium channel inhibitor, are crucial for controlling basal calcium current and essential for β-adrenergic augmentation of calcium influx in cardiomyocytes. Even with intact PKA signaling to other proteins modulating calcium handling, preventing adrenergic activation of calcium channels in Rad-phosphosite-mutant mice (4SA-Rad) has profound physiological effects: reduced heart rate with increased pauses, reduced basal contractility, near-complete attenuation of β-adrenergic contractile response and diminished …

Surgical And Oncological Outcomes Of Hepatic Resection For Hepatocellular Carcinoma: Report From A Low Volume Centre In A Developing Country, Muhammad Rizwan Khan, Saleema Begum, Muhammad Tayyab Ul Hasan Siddiqui

Section of General Surgery

Objective: To review the surgical and oncological outcomes of patients who underwent hepatic resection for hepatocellular carcinoma (HCC).
Study design: Cohort study.
Place and duration of study: Department of Surgery of the Aga Khan University Hospital Karachi, from 2008 to 2019.
Methodology: Consecutive patients who underwent hepatic resection for HCC at the Hospital were included. The data were collected and analysed on aspects including demographics, liver function status, tumour characteristics, perioperative management, and surgical and oncological outcomes. Survival analyses were performed using the Kaplan-Meier method, and log-rank test was applied to determine the influence of variables on overall and disease-free …

Time For Reintroducing Hpv Vaccine In Pakistan For Primary Prevention Of Cervical Cancer, Uzma Shamsi, Afshan Anwar, Zainab Samad

Community Health Sciences

No abstract provided.

Esophageal Carcinoma And Associated Risk Factors: A Case-Control Study In Two Tertiary Care Hospitals Of Kabul, Afghanistan, Ramin Saadaat, Jamshid Abdul-Ghafar, Ahmed Maseh Haidary, Nooria Atta, Tazeen Saeed Ali

Community Health Sciences

Purpose: Esophageal cancer (EC) is the most common cancer among males in Afghanistan, thus we aimed to conduct a case-control study to determine the associated risk factors with EC in two tertiary care hospitals of Kabul, Afghanistan.
Patients and methods: We enrolled 132 EC cases and 132 controls and used conditional logistic regression to estimate the odds ratio (OR) with consideration of 95% confidence interval (CI).
Results: The results of our study revealed that esophageal squamous cell carcinoma (ESCC) was the predominant type of EC constituting 75.8% of the cases. The results of the multivariate logistic analysis showed that males …

Neither Tumor-Infiltrating Lymphocytes Nor Cytotoxic T Cells Predict Enhanced Benefit From Chemotherapy In The Dbcg77b Phase Iii Clinical Trial, Elahe Shenasa, Elisabeth Specht Stovgaard, Maj-Britt Jensen, Karama Asleh, Nazia Riaz, Dongxia Gao, Samuel Leung, Bent Ejlertsen, Anne-Vibeke Laenkholm, Torsten O. Nielsen

Section of General Surgery

Recent studies have shown that immune infiltrates in the tumor microenvironment play a role in response to therapy, with some suggesting that patients with immunogenic tumors may receive increased benefit from chemotherapies. We evaluated this hypothesis in early breast cancer by testing the interaction between immune biomarkers and chemotherapy using materials from DBCG77B, a phase III clinical trial where high-risk premenopausal women were randomized to receive chemotherapy or no chemotherapy. Tissue microarrays were evaluated for tumor-infiltrating lymphocytes (TILs) assessed morphologically on hematoxylin and eosin-stained slides, and by immunohistochemistry for CD8, FOXP3, LAG-3, PD-1 and PD-L1. Following REMARK reporting guidelines, data …

Financial Toxicity Tumor Board: A Multi-Disciplinary Team Activity Required In Low And Middle-Income Countries (Lmic), Ahmed Nadeem Abbasi, Sohail Rasool, Laraib Khan

Department of Radiation Oncology

No abstract provided.

Association Of Trauma Center Designation With Postdischarge Survival Among Older Adults With Injuries, Molly P. Jarman, Ginger Jin, Joel S. Weissman, Arlene S. Ash, Jennifer Tjia, Ali Salim, Adil Haider, Zara Cooper

Section of General Surgery

Importance: Trauma centers improve outcomes for young patients with serious injuries. However, most injury-related hospital admissions and deaths occur in older adults, and it is not clear whether trauma center care provides the same benefit in this population.
Objective: To examine whether 30- and 365-day mortality of injured older adults is associated with the treating hospital's trauma center level.
Design, setting, and participants: This prospective, population-based cohort study used Medicare claims data from January 1, 2013, to December 31, 2016, for all fee-for-service Medicare beneficiaries 66 years or older with inpatient admission for traumatic injury in 2014 to 2015. Data …

What After Bcg Fails In Non-Muscle Invasive Bladder Cancer?, M Hammad Ather

Section of Urology

No abstract provided.

Toward A Topology-Based Therapeutic Design Of Membrane Proteins: Validation Of Napi2b Topology In Live Ovarian Cancer Cells, Leisan Bulatova, Daria Savenkova, Alsina Nurgalieva, Daria Reshetnikova, Arina Timonina, Vera Skripova, Mikhail Bogdanov, Ramziya Kiyamova

Faculty, Staff and Student Publications

NaPi2b is a sodium-dependent phosphate transporter that belongs to the SLC34 family of transporters which is mainly responsible for phosphate homeostasis in humans. Although NaPi2b is widely expressed in normal tissues, its overexpression has been demonstrated in ovarian, lung, and other cancers. A valuable set of antibodies, including L2 (20/3) and MX35, and its humanized versions react strongly with an antigen on the surface of ovarian and other carcinoma cells. Although the topology of NaPi2b was predicted

Conference Proceedings: Select Abstracts Presented At 2021 Advocate Aurora Health Scientific Day

Journal of Patient-Centered Research and Reviews

Abstracts published within this supplement were presented at the 47th annual Advocate Aurora Health Scientific Day, held virtually on May 26, 2021. This research symposium provides a forum for disseminating results from studies conducted by faculty, fellows, residents, and other allied health professionals associated with Midwest-based health system Advocate Aurora Health, which publishes the Journal of Patient-Centered Research and Reviews.

A New Paradigm: Ecmo Therapy In Pediatric Hematology/Oncology Patients, Igor Areinamo

Research Days

Background: The use of extracorporeal membrane oxygenation (ECMO) for support of pediatric patients has significantly increased in the past years. Patients with known oncologic diseases, immunodeficiencies, or bone marrow transplants (BMT) have traditionally not been considered candidates for Extracorporeal membrane oxygenation (ECMO) due to perceived high risk for mortality. Ongoing advances have continued to push the boundaries of ECMO use and we report our recent experience with this patient population

Objectives/Goal: To evaluate survival to discharge of pediatric patients who require ECMO support and who also have an underlying hematologic or oncologic disease process. To determine specific patient characteristics that …

Chronic Muscle Weakness And Mitochondrial Dysfunction In The Absence Of Sustained Atrophy In A Preclinical Sepsis Model, Allison M. Owen, Samir P. Patel, Jeffrey D. Smith, Beverly K. Balasuriya, Stephanie F. Mori, Gregory S. Hawk, Arnold J. Stromberg, Naohide Kuriyama, Masao Kaneki, Alexander G. Rabchevsky, Timothy A. Butterfield, Karyn A. Esser, Charlotte A. Peterson, Marlene E. Starr, Hiroshi Saito

Physiology Faculty Publications

Chronic critical illness is a global clinical issue affecting millions of sepsis survivors annually. Survivors report chronic skeletal muscle weakness and development of new functional limitations that persist for years. To delineate mechanisms of sepsis-induced chronic weakness, we first surpassed a critical barrier by establishing a murine model of sepsis with ICU-like interventions that allows for the study of survivors. We show that sepsis survivors have profound weakness for at least 1 month, even after recovery of muscle mass. Abnormal mitochondrial ultrastructure, impaired respiration and electron transport chain activities, and persistent protein oxidative damage were evident in the muscle of …

Improved Coordination Of Care For Picu Patients With Newly Diagnosed Anterior Mediastinal Masses, Laura Mccarthy

Presentations

This presentation describes a quality improvement project to develop a multi-disciplinary standardized approach for prompt surgical intervention to establish a diagnosis of anterior mediastinal mass. The aim was to decrease the time from presentation to surgical diagnostic procedure totreatment.

Meta-Regression: Prognostic Models As Objective Predictors Of Mortality Among Icu Cancer Patients, Sheila Donnell

Nursing Theses and Dissertations

Cancer patients admitted to the intensive care unit (ICU) may be experiencing complications of disease or treatment-related effects. While acute complications related to disease and/or its therapeutic management vary in severity, the approach to ICU-centered care is complicated by actual versus perceived risks of poor outcomes. Prognostic models that inform clinical judgment of nurses and physicians may prove helpful in this population. The Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) are ICU-based models predicting 30-day mortality among the general ICU population. Although studies have been …

Highlighting Trust In The Provision Of Cancer Care, Elizabeth Lazzara, Joseph Keebler, Soosi Day, Deborah Diazgranados, Minngui Pan, Mike King, Shin-Ping Tu

Publications

Slides:

• Patient Case
• Definition & Explanation of Trust
• Application of Trust to Cancer Case
• Implications for Clinical Care
• Implications for Research

Intensive Care In Oncology: Admission And Outcomes In Adult Patients With Cancer, Surya John

Honors Undergraduate Theses

Background: Historically, patients with cancer have been perceived as poor candidates for ICU admission. General ICU admission criteria lists cancer patients as low priority in ICU admission depriving them of the care they rightfully deserve. The purpose of this literary synthesis was to examine ICU admission criteria, risk factors, and outcomes of ICU admission in relation to hematological and solid tumor cancers and discuss ways that practitioners and nurses can educate patients with cancer and their families on appropriateness of ICU care.

Methods: A total of 768 articles were found in a literature search including all literature from 2005 to …

Improving Hand Hygiene Compliance To Reduce Clabsi Rate In Oncology Icu, Lorenzo D. San Pedro

Master's Projects and Capstones

The aim of this project is to reduce the rate of central line associated blood stream infection (CLABSI) occurrence in oncology ICU by 50% by the last quarter of 2015. This study was conducted in ICU to assess adherence to the facility’s hand hygiene (HH) protocol among the staff nurses and allied healthcare workers. The facility is best known as a non-profit cancer treatment center and designated as a Comprehensive Cancer Center. Evidence showed that hand hygiene is the most effective way of preventing CLABSI, one of the most common types of infection in ICU microsystem. The project utilized The …

Non-Small-Cell Lung Cancer Clinicopathologic Features And Survival Outcomes In Asian Pacific Islanders Residing In The United States: A Seer Analysis, M. S. Hamid, R. Shameem, K. Gafoor, J. George, B. Mina, K. Sullivan

Journal Articles

Background. The objective of our study was to ascertain racial/ethnic disparities in Asian/Pacific Islanders (API) for non-small-cell lung cancer (NSCLC) clinicopathologic features and survival outcomes based on various tumor characteristics and treatment modalities. Method. SEER database identified invasive NSCLC cases from 2004 to 2010. Variables included American Joint Committee on Cancer (AJCC) stage 7, tumor grade, tumor size, histology, age, marital status, radiation, surgery, and reason for no surgery. The Kruskall-Wallis test and the Z test were used to examine differences between races/ethnicities and the referent, non-Hispanic white (NHW). Multivariate Cox proportional analyses were used to establish the weight of …