Critical Care Commons^™

Beyond The Basics: Unraveling The Complexity Of Coronary Artery Calcification, Satwat Hashmi, Pashmina Wiqar Shah, Zouhair Aherrahrou, Elena Aikawa, Rédouane Aherrahrou

Department of Biological & Biomedical Sciences

Coronary artery calcification (CAC) is mainly associated with coronary atherosclerosis, which is an indicator of coronary artery disease (CAD). CAC refers to the accumulation of calcium phosphate deposits, classified as micro- or macrocalcifications, that lead to the hardening and narrowing of the coronary arteries. CAC is a strong predictor of future cardiovascular events, such as myocardial infarction and sudden death. Our narrative review focuses on the pathophysiology of CAC, exploring its link to plaque vulnerability, genetic factors, and how race and sex can affect the condition. We also examined the connection between the gut microbiome and CAC, and the impact …

Allergic Bronchopulmonary Aspergillosis: Radiological And Microbiological Profile Of Patients Presented In An Outpatient Pulmonary Clinic In A Developing Country, Nousheen Iqbal, Muhammad Irfan, Mustafa Bin Ali Zubairi, Maaha Ayub, Safia Awan, Kauser Jabeen, Ali Bin Sarwar Zubairi

Section of Pulmonary & Critical Care

There is limited data available about allergic bronchopulmonary aspergillosis (ABPA) in Pakistan. The aim of the study was to describe the radiological and microbiological profile of ABPA patients presenting to the outpatient pulmonary clinic of a tertiary care hospital in Karachi, Pakistan. A retrospective study was conducted on ABPA patients who presented to the pulmonary outpatient clinic at Aga Khan University Hospital, Karachi, Pakistan, from January 2017 to December 2019. Data was collected on microbiology and radiology features on predesigned proforma. A total of 7759 asthmatic patients presented at the outpatient pulmonology clinic during the study period. Of the 245 …

Variability In Provider Assessment Of Sepsis And Potential Of Host Response Technology To Address This Dilemma—Results Of An Online Delphi Study, Chadd K. Kraus, Hollis R. O’Neal, Nathan A. Ledeboer, Todd W. Rice, Wesley H. Self, Richard E. Rothman

School of Medicine Faculty Publications

Potentially septic patients have a huge clinical and economic impact on hospitals and often present to the emergency department (ED) with undifferentiated symptoms. The triage of these patients is complex and has historically relied heavily upon provider judgment. This study aims to evaluate the consistency of provider judgment and the potential of a new host response sepsis test to aid in the triage process. A modified Delphi study involving 26 participants from multiple specialties was conducted to evaluate provider agreement about sepsis risk and to test proposed actions based on the results of a sepsis test. The participants considered case …

Massive Transfusion And Shock Index, Kasey House

MSN Capstone Projects

Hemorrhagic shock is one of the leading causes of preventable death in military trauma patients. Literature shows that pre-hospital transfusions of blood products within the combat environment have shown to have a greater likelihood of survival. This has produced a challenge in the pre-hospital setting to have a standardized method of predicting the patient’s need for a massive transfusion. In the last few years, the development of a Massive Transfusion Protocol (MTP) has become the standard to quickly deliver blood products to actively bleeding patients. Every minute waiting to administer blood products increases mortality by 5%.

While initiating an MTP …

Pulmonary & Critical Care Insider: Issue 4, Bharat Bajantri Md, Sarah Ellsworth-Hoffman Mls

Critical Care & Pulmonary

Pulmonary & Critical Care Insider Issue 4

Compiled by Bharat Bajantri, MD, and librarian Sarah Ellsworth, MLS for the clinicians of the Pulmonary and Critical Care team of Parkview.

The goal of this newsletter is to give a brief summary of the most pertinent articles to everyday practice and an attempt to keep up with literature as best as possible. Newsletters go out every 1-2 months.

Summaries/Topics in this issue:

• Inside Medicine- Ozempic

• Inhaled Amikacin for VAP (AMIKINHAL Trial)

• 2023 GOLD Guidelines for COPD

• SAGA of Antibiotics in the ICU

• The MANDALA trial

• The DENALI trial

• RESCUE IHCA – Not …

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Pulmonary & Critical Care Insider: Special Issue 5: 2023 In Review, Bharat Bajantri Md, Sarah Ellsworth-Hoffman Mls

Critical Care & Pulmonary

Pulmonary & Critical Care Insider Issue 5: Special Issue

Compiled by Bharat Bajantri, MD, and librarian Sarah Ellsworth, MLS for the clinicians of the Pulmonary and Critical Care team of Parkview.

The goal of this newsletter is to give a brief summary of the most pertinent articles to everyday practice and an attempt to keep up with literature as best as possible. Newsletters go out every 1-2 months.

Pakistan Study Of Premature Coronary Atherosclerosis In Young Adults (Pak-Sehat): A Prospective Longitudinal Study Protocol Investigating The Prevalence, Severity And Determinants Of Atherosclerotic Cardiovascular Disease In The Young Adult Pakistani Population, Bashir Hanif, Sana Sheikh, Ghazal Peerwani, Miguel Cainzos-Achirica, Wajiha Javed, Jaffer Bin Baqar, Zainab Samad, Faiza Bashir, Salim S. Virani, Khurram Nasir

Section of Cardiology

Introduction: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity, mortality and health expenditures worldwide. Despite having higher ASCVD in the Pakistani population, data on subclinical coronary atherosclerosis in young Pakistanis remain scarce. The PAKistan Study of prEmature coronary atHerosclerosis in young AdulTs (PAK-SEHAT) aims to assess the prevalence, severity and determinants of subclinical coronary atherosclerosis among Pakistani men (35-60 years) and women (35-65 years) free of clinically symptomatic ASCVD and will assess 5-year rates of ASCVD events.
Methods and analysis: PAK-SEHAT is an ongoing prospective cohort study with 2000 participants from all provinces of Pakistan who will be …

Oral Sucrose And The Relation To Neonatal Pain Perception, Meagan L. Burns

MSN Capstone Projects

Pain is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage” (Treede, 2018). The phenomenon of pain is a personal and unique experience that many of the world’s population has experienced in some form or fashion throughout their lifetime. Neonates are exposed to many painful procedures and/or situations due to various medical ailments that may require a neonatal intensive care unit (NICU) admission. Infants have a special place in the hearts of adults all over the world, and any interventions that would increase the likelihood of diminishing or removing perceived pain in this population are likely …

Ten Steps Toward Improving In-Hospital Cardiac Arrest Quality Of Care And Outcomes, Brahmajee K. Nallamothu, Robert Greif, Theresa Anderson, Huba Atiq, Thomaz Bittencourt Couto, Julie Considine, Allan R De Caen, Therese Djärv, Ann Doll, Matthew J. Douma

Department of Anaesthesia

No abstract provided.

Methodological Analysis Of A Community-Based Training Initiative Using The Epis Framework: An Ongoing Initiative To Empower 10 Million Bystanders In Cpr And Bleeding Control, Asma Altaf Hussain Merchant, Sheza Hassan, Mirza Noor Ali Baig, Huba Atiq, Sana Mahmood, Adil H. Haider, Zia Ul Haq, Deeba Shehnaz, Rizwan Naseer, Junaid Razzak

Medical College Documents

Background: Out-of-hospital cardiac arrest (OHCA) and life-threatening bleeding from trauma are leading causes of preventable mortality globally. Early intervention from bystanders can play a pivotal role in increasing the survival rate of victims. While great efforts for bystander training have yielded positive results in high-income countries, the same has not been replicated in low and middle-income countries (LMICs) due to resources constraints. This article describes a replicable implementation model of a nationwide program, aimed at empowering 10 million bystanders with basic knowledge and skills of hands-only cardiopulmonary resuscitation (CPR) and bleeding control in a resource-limited setting.
Methods: Using the EPIS …

Clinical Characteristics And Treatment Outcome Of Paediatric Non-Hodgkin's Lymphoma At A Tertiary Care Hospital In Pakistan, Juverya Naqvi, Mir Ibrahim Sajid, Saiqa Khan, Zaib Un Nisa Kamran, Zehra Fadoo

Medical College Documents

Objectives: To highlight the clinical characteristics of paediatric patients presenting with non-Hodgkin's lymphoma, treatment toxicities, and outcome.
Methods: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data of all paediatric patients aged 0-18 years diagnosed with non-Hodgkin's lymphoma from 2010 to 2020. Demographic characteristics, presentation, treatment provided, complications, if any, and treatment outcome were recorded. Data was analysed using SPSS 21.
Results: Of the 92 patients, 69(75.0%) were males. The overall mean age was 14.35±5.80 years. The most common presenting complaint was pyrexia 42(45.7%), the most common diagnosis was Burkitt lymphoma 40(43.5%), the most …

Sustaining Care Team Engagement Using A Hierarchy Of Needs Framework, Katherine Skroski, Sam Canonico, Hailey Frager, Mary Beeaker, Natalia Johnson, Rebecca A. Brookes

Operations Transformation

Cardiology Intensive Care & Cardiovascular Interventional (CICU & R9 West) teams provide superb care to critically ill cardiac patients at Maine Medical Center. Covid Pandemic revealed the importance of physical and mental health wellbeing, as well as care team engagement in order to continue to provide outstanding care to patients. CICU/R9 West Leadership looked for ways to improve team engagement and ensure that care team members’ needs are met and sustained.

Identification Of Post-Cardiac Arrest Blood Pressure Thresholds Associated With Outcomes In Children: An Icu-Resuscitation Study, Monique M Gardner, David A Hehir, Ron W Reeder, Tageldin Ahmed, Michael J Bell, Robert A Berg, Robert Bishop, Matthew Bochkoris, Candice Burns, Joseph A Carcillo, Todd C Carpenter, J Michael Dean, J Wesley Diddle, Myke Federman, Richard Fernandez, Ericka L Fink, Deborah Franzon, Aisha H Frazier, Stuart H Friess, Kathryn Graham, Mark Hall, Monica L Harding, Christopher M Horvat, Leanna L Huard, Tensing Maa, Arushi Manga, Patrick S Mcquillen, Kathleen L Meert, Ryan W Morgan, Peter M Mourani, Vinay M Nadkarni, Maryam Y Naim, Daniel Notterman, Murray M Pollack, Anil Sapru, Carleen Schneiter, Matthew P Sharron, Neeraj Srivastava, Bradley Tilford, Shirley D. Viteri, David Wessel, Heather A Wolfe, Andrew R Yates, Athena F Zuppa, Robert M Sutton, Alexis A Topjian

Department of Medicine Faculty Papers

INTRODUCTION: Though early hypotension after pediatric in-hospital cardiac arrest (IHCA) is associated with inferior outcomes, ideal post-arrest blood pressure (BP) targets have not been established. We aimed to leverage prospectively collected BP data to explore the association of post-arrest BP thresholds with outcomes. We hypothesized that post-arrest systolic and diastolic BP thresholds would be higher than the currently recommended post-cardiopulmonary resuscitation BP targets and would be associated with higher rates of survival to hospital discharge.

METHODS: We performed a secondary analysis of prospectively collected BP data from the first 24 h following return of circulation from index IHCA events enrolled …

Pulmonary & Critical Care Insider: Issue 3, Bharat Bajantri Md, Sarah Ellsworth-Hoffman Mls

Critical Care & Pulmonary

Pulmonary & Critical Care Insider Issue 3

Compiled by Bharat Bajantri, MD, and librarian Sarah Ellsworth, MLS for the clinicians of the Pulmonary and Critical Care team of Parkview.

The goal of this newsletter is to give a brief summary of the most pertinent articles to everyday practice and an attempt to keep up with literature as best as possible. Newsletters go out every 1-2 months.

Summaries/Topics in this issue:

Lactated Ringer's or Normal Saline in Acute Pancreatitis?

Don’t complain about too many CT scans being ordered by your ED doctor!

Stroke care for intensivists – Not as complicated after …

Cocaine Use Disorder Effects On Blood Oxytocin Levels And Oxtr Dna Methylation, Manassés Soares Souza, Breno Sanvicente-Vieira, Aline Zaparte, Talita Baptista, Maria Aparecida Nagai, Flávia Rotea Mangone, Ana Carolina Pavanelli, Thiago Wendt Viola, Rodrigo Grassi-Oliveira

School of Medicine Faculty Publications

Substance use disorders have been associated with alterations in the oxytocinergic system, but few studies have investigated both the peptide and epigenetic mechanisms potentially implicated in the regulation of oxytocin receptor. In this study, we compared plasma oxytocin and blood DNA methylation in the OXTR gene between people with and without cocaine use disorder (CUD). We measured the oxytocin levels of 51 people with CUD during acute abstinence and of 30 healthy controls using an enzyme immunoassay. The levels of DNA methylation in four CpG sites at exon III of the OXTR gene were evaluated in a subsample using pyrosequencing. …

Outcomes Of Patients With Intermediate Risk Pulmonary Embolism Treated With A Multidisciplinary Pulmonary Embolism Response Team. The Emergent Role Of Percutaneous Catheter Thrombectomy And The Importance Of Cardiac Surgery Engagement, Juan N Pulido, Robert Fletcher, Michelle A. Poitevin, Kristina Pratt, Paul P Huang, George P Pappas, Eric J Lehr

Articles, Abstracts, and Reports

Background: Management of Intermediate Risk Pulmonary Embolism (IRPE) remains controversial due to the dynamic nature of the disease and the lack of correlative outcomes with large clot burden. We describe the outcomes of patients presenting with IRPE managed by a multidisciplinary Pulmonary Embolism Response Team (PERT).

Methods: This single center retrospective study included EMR data from patients that were a part of the multidisciplinary PERT program from January 2012 to June 2023. PERT was activated if risk of death was intermediate or higher. The simplified pulmonary embolism severity index (sPESI) and Bova score were used as risk stratification tools. Patients …

Role Of A Multidisciplinary Pulmonary Embolism Response Team And Impact Of Interventional Therapy In The Management Of Patients With Intermediate-High Risk Pulmonary Embolism, Juan N Pulido, Robert Fletcher, Michelle A. Poitevin, Kristina Pratt, Paul P Huang, Eric J Lehr, George P Pappas

Articles, Abstracts, and Reports

Background: Despite emerging interventional options for pulmonary embolism (PE), the mortality rate for intermediate high-risk PE (IHR-PE) remains high and the optimal therapeutic approach unclear due to a lack of robust outcomes data. We describe the outcomes of patients presenting with IHR-PE managed by a multidisciplinary PERT program with all available reperfusion options.

Methods: This single center retrospective study included EMR data from patients that were a part of the multidisciplinary PERT program from January 2012 to June 2023. PERT was activated if risk of death was intermediate or higher. The simplified pulmonary embolism severity index (sPESI) and Bova score …

Pulmonary & Critical Care Insider: Issue 2, Bharat Bajantri Md, Sarah Ellsworth Mls

Critical Care & Pulmonary

Pulmonary & Critical Care Insider Issue 2

Compiled by Bharat Bajantri, MD, and librarian Sarah Ellsworth, MLS for the clinicians of the Pulmonary and Critical Care team of Parkview.

The goal of this newsletter is to give a brief summary of the most pertinent articles to everyday practice and an attempt to keep up with literature as best as possible. Newsletters go out every 1-2 months.

Summaries/Topics in this issue:

• Spontaneous Breathing Trials
• Enteral feedings
• EFFORT Protein trial
• The NUTRIREA-3 trial
• Veno-venous extracorporeal carbon dioxide removal (vv-ECCO2 R)
• Acute hypoxemic respiratory failure (AHRF)
• Penicillin allergy
• PEN-FAST score
• Etomidate increases mortality …

Pulmonary & Critical Care Insider: Issue 1, Bharat Bajantri Md, Sarah Ellsworth Mls

Critical Care & Pulmonary

Pulmonary & Critical Care Insider Issue 1

Compiled by Bharat Bajantri, MD, and librarian Sarah Ellsworth, MLS for the clinicians of the Pulmonary and Critical Care team of Parkview.

The goal of this newsletter is to give a brief summary of the most pertinent articles to everyday practice and an attempt to keep up with literature as best as possible. Newsletters go out every 1-2 months.

Summaries/Topics in this issue:

• Comparison of two commonly prescribed regimens of empiric antibiotics.
• Vancomycin and piperacillin-tazobactam (VPT)
• The efficacy and safety of Dupilumab in patients with COPD
• The BOREAS trial
• Simple aspiration versus chest …

Mechanically Ventilated Covid-19 Patients Admitted To The Intensive Care Unit In The United States With Or Without Respiratory Failure Secondary To Covid-19 Pneumonia: A Retrospective Comparison Of Characteristics And Outcomes, Jesse Johnson, Kashka F. Mallari, Vincent Pepe, Taylor Treacy, Gregory Mcdonough, P. Khaing, Christopher Mcgrath, Brandon George, Erika J. Yoo

Division of Pulmonary and Critical Care Medicine Faculty Papers

BACKGROUND: There is increasing heterogeneity in the clinical phenotype of patients admitted to the intensive care unit (ICU) with coronavirus disease 2019 (COVID-19,) and reasons for mechanical ventilation are not limited to COVID pneumonia. We aimed to compare the characteristics and outcomes of intubated patients admitted to the ICU with the primary diagnosis of acute hypoxemic respiratory failure (AHRF) from COVID-19 pneumonia to those patients admitted for an alternative diagnosis.

METHODS: Retrospective cohort study of adults with confirmed SARS-CoV-2 infection admitted to nine ICUs between March 18, 2020, and April 30, 2021, at an urban university institution. We compared characteristics …

Adenosine Metabolized From Extracellular Atp Ameliorates Organ Injury By Triggering A2br Signaling, Taha Kelestemur, Zoltán H Németh, Pal Pacher, Jennet Beesley, Simon C Robson, Holger K Eltzschig, György Haskó

Journal Articles

BACKGROUND: Trauma and a subsequent hemorrhagic shock (T/HS) result in insufficient oxygen delivery to tissues and multiple organ failure. Extracellular adenosine, which is a product of the extracellular degradation of adenosine 5' triphosphate (ATP) by the membrane-embedded enzymes CD39 and CD73, is organ protective, as it participates in signaling pathways, which promote cell survival and suppress inflammation through adenosine receptors including the A

METHODS: T/HS shock was induced by blood withdrawal from the femoral artery in wild-type, global knockout (CD39, CD73, A

RESULTS: T/HS upregulated the expression of CD39, CD73, and the A

CONCLUSION: In conclusion, the CD39-CD73-A

Prognostic And Predictive Value Of Endothelial Dysfunction Biomarkers In Sepsis-Associated Acute Kidney Injury: Risk-Stratified Analysis From A Prospective Observational Cohort Of Pediatric Septic Shock., Mihir R. Atreya, Natalie Z. Cvijanovich, Julie C. Fitzgerald, Scott L. Weiss, Michael T. Bigham, Parag N. Jain, Adam J. Schwarz, Riad Lutfi, Jeffrey Nowak, Geoffrey L. Allen, Neal J. Thomas, Jocelyn R. Grunwell, Torrey Baines, Michael Quasney, Bereketeab Haileselassie, Matthew N. Alder, Stuart L. Goldstein, Natalja L. Stanski

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is associated with high morbidity, with no current therapies available beyond continuous renal replacement therapy (CRRT). Systemic inflammation and endothelial dysfunction are key drivers of SA-AKI. We sought to measure differences between endothelial dysfunction markers among children with and without SA-AKI, test whether this association varied across inflammatory biomarker-based risk strata, and develop prediction models to identify those at highest risk of SA-AKI.

METHODS: Secondary analyses of prospective observational cohort of pediatric septic shock. Primary outcome of interest was the presence of ≥ Stage II KDIGO SA-AKI on day 3 based on serum creatinine …

A Health Systems Approach To Critical Care Delivery In Low-Resource Settings: A Narrative Review, Stephen A. Spencer, Faustina Excel Adipa, Tim Baker, Ana Maria Crawford, Paul Dark, Dingase Dula, Stephen B. Gordon, David Oliver Hamilton, Dawit Kebede Huluka, Wangari Siika

Anaesthesiology, East Africa

There is a high burden of critical illness in low-income countries (LICs), adding pressure to already strained health systems. Over the next decade, the need for critical care is expected to grow due to ageing populations with increasing medical complexity; limited access to primary care; climate change; natural disasters; and conflict. In 2019, the 72nd World Health Assembly emphasised that an essential part of universal health coverage is improved access to effective emergency and critical care and to “ensure the timely and effective delivery of life-saving health care services to those in need”. In this narrative review, we examine critical …

Calculating Differences In Surrogate Lung Perfusion Measurements Between Smokers And Nonsmokers As A Biomarker To Assess Their Potentials For Developing Chronic Obstructive Pulmonary Disease, A Prakash, A Nowacki, Y K. Liu, J Cisneros-Paz, Girish Nair, E Castillo

Conference Presentation Abstracts

Purpose: COPD (chronic obstructive pulmonary disease) is a collection of lung diseases that complicates breathing and causes irreversible lung damage. Given that it is a progressive disease, early detection is crucial for managing its symptoms. We recently developed a method for calculating pulmonary blood mass change (PBMC) apparent on paired inhale/exhale non-contrast computed tomography (CT) scans as a quantitative surrogate for lung perfusion. Our long term objective is to develop a PBMC biomarker for predicting COPD progression. As a first step, we hypothesize that PBMC is significantly lower for non-COPD smokers versus non-COPD non-smokers. Methods: CT scans from 77 healthy …

Timing Of Invasive Mechanical Ventilation And Death In Critically Ill Adults With Covid-19: A Multicenter Cohort Study., Adam Green, Jean-Sebastien Rachoin, Christa Schorr, Phil Dellinger, Jonathan D Casey, Isabel Park, Shruti Gupta, Rebecca M Baron, Shahzad Shaefi, Krystal Hunter, David E Leaf

Cooper Medical School of Rowan University Faculty Scholarship

PURPOSE: To investigate if the timing of initiation of invasive mechanical ventilation (IMV) for critically ill patients with COVID-19 is associated with mortality.

MATERIALS AND METHODS: The data for this study were derived from a multicenter cohort study of critically ill adults with COVID-19 admitted to ICUs at 68 hospitals across the US from March 1 to July 1, 2020. We examined the association between early (ICU days 1-2) versus late (ICU days 3-7) initiation of IMV and time-to-death. Patients were followed until the first of hospital discharge, death, or 90 days. We adjusted for confounding using a multivariable Cox …

Detrimental Effects Of Pcsk9 Loss-Of-Function In The Pediatric Host Response To Sepsis Are Mediated Through Independent Influence On Angiopoietin-1., Mihir R. Atreya, Natalie Z. Cvijanovich, Julie C. Fitzgerald, Scott L. Weiss, Michael T. Bigham, Parag N. Jain, Adam J. Schwarz, Riad Lutfi, Jeffrey Nowak, Geoffrey L. Allen, Neal J. Thomas, Jocelyn R. Grunwell, Torrey Baines, Michael Quasney, Bereketeab Haileselassie, Matthew N. Alder, Patrick Lahni, Scarlett Ripberger, Adesuwa Ekunwe, Kyle R. Campbell, Keith R. Walley, Stephen W. Standage

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Sepsis is associated with significant mortality. Yet, there are no efficacious therapies beyond antibiotics. PCSK9 loss-of-function (LOF) and inhibition, through enhanced low-density lipoprotein receptor (LDLR) mediated endotoxin clearance, holds promise as a potential therapeutic approach among adults. In contrast, we have previously demonstrated higher mortality in the juvenile host. Given the potential pleiotropic effects of PCSK9 on the endothelium, beyond canonical effects on serum lipoproteins, both of which may influence sepsis outcomes, we sought to test the influence of PCSK9 LOF genotype on endothelial dysfunction.

METHODS: Secondary analyses of a prospective observational cohort of pediatric septic shock. Genetic variants …

Blm Overexpression As A Predictive Biomarker For Chk1 Inhibitor Response In Parp Inhibitor–Resistant Brca-Mutant Ovarian Cancer, Nitasha Gupta, Tzu-Ting Huang, Jayakumar R Nair, Daniel An, Grant Zurcher, Erika J Lampert, Ann Mccoy, Ashley Cimino-Mathews, Elizabeth M Swisher, Marc R Radke, Christina M Lockwood, Jonathan B Reichel, Chih-Yuan Chiang, Kelli M Wilson, Ken Chih-Chien Cheng, Darryl Nousome, Jung-Min Lee

Journal Articles

Poly(ADP-ribose) polymerase inhibitors (PARPis) have changed the treatment paradigm in breast cancer gene (BRCA)–mutant high-grade serous ovarian carcinoma (HGSC). However, most patients eventually develop resistance to PARPis, highlighting an unmet need for improved therapeutic strategies. Using high-throughput drug screens, we identified ataxia telangiectasia and rad3-related protein/checkpoint kinase 1 (CHK1) pathway inhibitors as cytotoxic and further validated the activity of the CHK1 inhibitor (CHK1i) prexasertib in PARPi-sensitive and -resistant BRCA-mutant HGSC cells and xenograft mouse models. CHK1i monotherapy induced DNA damage, apoptosis, and tumor size reduction. We then conducted a phase 2 study (NCT02203513) of prexasertib …

Targeting Myocardial Equilibrative Nucleoside Transporter Ent1 Provides Cardioprotection By Enhancing Myeloid Adora2b Signaling., Wei Ruan, Jiwen Li, Seungwon Choi, Xinxin Ma, Yafen Liang, Ragini Nair, Xiaoyi Yuan, Tingting W Mills, Holger K Eltzschig

Journal Articles

Previous studies implicate extracellular adenosine signaling in attenuating myocardial ischemia and reperfusion injury (IRI). This extracellular adenosine signaling is terminated by its uptake into cells by equilibrative nucleoside transporters (ENTs). Thus, we hypothesized that targeting ENTs would function to increase cardiac adenosine signaling and concomitant cardioprotection against IRI. Mice were exposed to myocardial ischemia and reperfusion injury. Myocardial injury was attenuated in mice treated with the nonspecific ENT inhibitor dipyridamole. A comparison of mice with global Ent1 or Ent2 deletion showed cardioprotection only in Ent1-/- mice. Moreover, studies with tissue-specific Ent deletion revealed that mice with myocyte-specific Ent1 deletion (Ent1loxP/loxP …

Implementation Of A Virtual Interprofessional Icu Learning Collaborative: Successes, Challenges, And Initial Reactions From The Structured Team- Based Optimal Patient-Centered Care For Virus Covid-19 Collaborators, Simon Zec, Nika Zorko Garbajs, Yue Dong, Ognjen Gajic, Christina Kordik, Lori Harmon, Marija Bogojevic, Romil Singh, Yuqiang Sun, Vikas Bansal, Linh Vu, Kelly Cawcutt, John M. Litell, Sarah Redmond, Elly Fitzpatrick, Kirstin J. Kooda, Michelle Biehl, Neha S. Dangayach, Viren Kaul, June M. Chae, Aaron Leppin, Mathew Siuba, Rahul Kashyap, Allan J. Walkey, Alexander S. Niven

Jefferson Hospital Staff Papers and Presentations

IMPORTANCE: Initial Society of Critical Care Medicine Discovery Viral Infection and Respiratory illness Universal Study (VIRUS) Registry analysis suggested that improvements in critical care processes offered the greatest modifiable opportunity to improve critically ill COVID-19 patient outcomes. OBJECTIVES: The Structured Team-based Optimal Patient-Centered Care for Virus COVID-19 ICU Collaborative was created to identify and speed implementation of best evidence based COVID-19 practices. DESIGN, SETTING, AND PARTICIPANTS: This 6-month project included volunteer interprofessional teams from VIRUS Registry sites, who received online training on the Checklist for Early Recognition and Treatment of Acute Illness and iNjury approach, a structured and systematic method …

Quantifying Disease Progression In Copd Patients By Forecasting Pft Scores Using Extracted Features From Non-Contrast Ct, A T. Luong, C J. Herrera, E Young, Y K. Liu, A Nowacki, J Cisneros-Paz, Girish Nair, E Castillo

Conference Presentation Abstracts

Purpose: Currently there is no validated method for quantifying risk of disease progression in chronic obstructive pulmonary disease (COPD). We aim to address this by predicting whether a patient will worsen using a machine learning model trained on basic patient information, current pulmonary function values, FEV1 and FVC, and extracted features from a non-contrast CT scan. Disease severity is characterized by these pulmonary function values, and by extension disease progression can be determined by the change in these values between future timepoints. Methods: XGBoost, a popular classification library that utilizes gradient boosted trees, was used to define an ensemble model …