Medicine and Health Sciences Commons^™

Drugs For Preventing Red Blood Cell Dehydration In People With Sickle Cell Disease., Srikanth Nagalla, Samir K. Ballas

Cardeza Foundation for Hematologic Research

BACKGROUND: Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. This is an updated version of a previously published review.

OBJECTIVES: To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells.

SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic …

Role Of The Fractalkine Receptor In Cns Autoimmune Inflammation: New Approach Utilizing A Mouse Model Expressing The Human Cx3cr1, Sandra M. Cardona, Sangwon V. Kim, Kaira A. Church, Vanessa O. Torres, Ian A. Cleary, Andrew S. Mendiola, Stephen P. Saville, Stephanie S. Watowich, Jan Parker-Thornburg, Alejandro Soto-Ospina, Pedronel Araque, Richard M. Ransohoff, Astrid E. Cardona

Department of Microbiology and Immunology Faculty Papers

Multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS) is the leading cause of non-traumatic neurological disability in young adults. Immune mediated destruction of myelin and oligodendrocytes is considered the primary pathology of MS, but progressive axonal loss is the major cause of neurological disability. In an effort to understand microglia function during CNS inflammation, our laboratory focuses on the fractalkine/CX3CR1 signaling as a regulator of microglia neurotoxicity in various models of neurodegeneration. Fractalkine (FKN) is a transmembrane chemokine expressed in the CNS by neurons and signals through its unique receptor CX3CR1 present in microglia. During …

Low-Cost, Low Fidelity Meat Model To Teach Ultrasound Guided Nerve Blocks, Morgan Oakland, Shruti Chandra, Carl Alsup

Department of Emergency Medicine Faculty Papers

Audience: The target audience of this workshop is emergency medicine residents; however, it is appropriate for all level of learners from medical students to faculty.

Introduction: Pain control is a major focus in the emergency department. Regional anesthesia is a rapidly growing alternative to opioid analgesia or procedural sedation. Nerve blocks are useful in many procedures and are relevant to some of our most common chief complaints. Ultrasound guided regional anesthesia has been shown to be highly successful with minimal complications, and has been shown to reduce the need for supplemental anesthesia such as sedation and narcotics.¹ Ultrasound guidance …

Dti Metrics For Multi-Site/Multi-Scanner Study Of Adult Cervical Spinal Cord, Devon M. Middleton, Phd, Joshua Fisher, Bs, Adam E. Flanders, Md, Feroze Mohamed, Phd, John H. Wu, Md, Laura Krisa, Phd, Mark Elliot, Phd, Scott H. Faro, Md, Jessica Evans, Bs

Department of Radiology Posters

Background and Objective

A major variable in DTI spinal cord studies is the diversity in MRI scanner vendor and field strength. While there are several techniques proven to acquire DTI data, there are no standardized accepted methods for acquisition and processing. As more medical systems are utilizing this technology to evaluate the spinal cord, it is important to study the reproducibility of the DTI metrics among various scanner platforms, coil configurations and software implementations to determine the variance in obtaining normative spinal cord DTI data. This preliminary data for a multi-site DTI study examines the effects of these different MR …

Metformin Clinical Trial In Hpv+ And Hpv- Head And Neck Squamous Cell Carcinoma: Impact On Cancer Cell Apoptosis And Immune Infiltrate., Joseph M. Curry, Jennifer Johnson, Mehri Mollaee, Patrick Tassone, Dev Amin, Alexander Knops, Diana Whitaker Menezes, My Mahoney, Andrew P. South, Ulrich Rodeck, Tingting Zhan, Larry A. Harshyne, Nancy Philp, Adam J. Luginbuhl, David Cognetti, Madalina Tuluc, Ubaldo E. Martinez-Outshoorn, Md

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Background: Metformin, an oral anti-hyperglycemic drug which inhibits mitochondrial complex I and oxidative phosphorylation has been reported to correlate with improved outcomes in head and neck squamous cell carcinoma (HNSCC) and other cancers. This effect is postulated to occur through disruption of tumor-driven metabolic and immune dysregulation in the tumor microenvironment (TME). We report new findings on the impact of metformin on the tumor and immune elements of the TME from a clinical trial of metformin in HNSCC. Methods: Human papilloma virus-(HPV-) tobacco+ mucosal HNSCC samples (n = 12) were compared to HPV+ oropharyngeal squamous cell carcinoma (OPSCC) samples (n …

3,3'-Diindolylmethane Enhances Apoptosis In Docetaxel-Treated Breast Cancer Cells By Generation Of Reactive Oxygen Species., Susan Lanza-Jacoby, Guanjun Cheng

Department of Surgery Faculty Papers

CONTEXT: A major problem in the treatment of cancer is the development of toxic side effects and resistance to chemotherapy. The use of plant compounds to overcome resistance and prevent toxicity is a potential strategy for treatment.

OBJECTIVE: We evaluated whether 3,3'-diindolylmethane (DIM) enhanced the sensitivity of breast cancer cells to docetaxel (DOC).

MATERIALS AND METHODS: MDA-MB231 and Sk-BR-3 cells were treated with and without 25 or 50 µM of DIM and 1 nM of DOC for 48 and 72 h, respectively. MTT assay was used to measure cell survival. Apoptosis and intracellular reactive oxygen species (ROS) were determined by …

Early And Late Complications Of Bariatric Operation., Robert Lim, Alec Beekley, Dirk C. Johnson, Kimberly A. Davis

Department of Surgery Faculty Papers

Weight loss surgery is one of the fastest growing segments of the surgical discipline. As with all medical procedures, postoperative complications will occur. Acute care surgeons need to be familiar with the common problems and their management. Although general surgical principles generally apply, diagnoses specific to the various bariatric operations must be considered. There are anatomic considerations which alter management priorities and options for these patients in many instances. These problems present both early or late in the postoperative course. Bariatric operations, in many instances, result in permanent alteration of a patient's anatomy, which can lead to complications at any …

Mitochondrial Fusion And Bid-Mediated Mitochondrial Apoptosis Are Perturbed By Alcohol With Distinct Dependence On Its Metabolism, Shamim Naghdi, William S. Slovinsky, Muniswamy Madesh, Emanual Rubin, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Environmental stressors like ethanol (EtOH) commonly target mitochondria to influence the cell’s fate. Recent literature supports that chronic EtOH exposure suppresses mitochondrial dynamics, central to quality control, and sensitizes mitochondrial permeability transition pore opening to promote cell death. EtOH-induced tissue injury is primarily attributed to its toxic metabolic products but alcoholism also impairs tissues that poorly metabolize EtOH. We embarked on studies to determine the respective roles of EtOH and its metabolites in mitochondrial fusion and tBid-induced mitochondrial apoptosis. We used HepG2 cells that do not metabolize EtOH and its engineered clone that expresses EtOH-metabolizing Cytochrome P450 E2 and alcohol …

Microtubule-Associated Protein 1 Light Chain 3b, (Lc3b) Is Necessary To Maintain Lipid-Mediated Homeostasis In The Retinal Pigment Epithelium., Anuradha Dhingra, Brent A Bell, Neal S. Peachey, Lauren L. Daniele, Juan Reyes-Reveles, Rachel C. Sharp, Bokkyoo Jun, Nicolas G. Bazan, Janet R. Sparrow, Hye Jin Kim, Nancy J. Philp, Kathleen Boesze-Battaglia

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Like other neurons, retinal cells utilize autophagic pathways to maintain cell homeostasis. The mammalian retina relies on heterophagy and selective autophagy to efficiently degrade and metabolize ingested lipids with disruption in autophagy associated degradation contributing to age related retinal disorders. The retinal pigment epithelium (RPE) supports photoreceptor cell renewal by daily phagocytosis of shed photoreceptor outer segments (OS). The daily ingestion of these lipid-rich OS imposes a constant degradative burden on these terminally differentiated cells. These cells rely on Microtubule-Associated Protein 1 Light Chain 3 (LC3) family of proteins for phagocytic clearance of the ingested OS. The LC3 family comprises …

The Sensitivity Of Cross-Sectional Imaging For Identifying Periampullary Diverticula, Austin Chiang, Md, Mph, Jetmir Vojnika, Md, Alexander Schlachterman, Md, David E. Loren, Md, Thomas E. Kowalski

Division of Gastroenterology and Hepatology Posters

Our aim was to determine the sensitivity of imaging in identifying duodenal diverticula as seen during ERCP.

Teaching Tools And Communication Solutions, Jennifer Wilson, Ms, Els, Anthony Frisby, Phd

Program Directors Retreat

No abstract provided.

Labarchives: An Electronic Research Notebook For Jefferson, Gary Kaplan, Mslis, Ahip, Anthony Frisby, Phd, Jessica Gutierrez, Bs, Theodore Taraschi, Phd, Timothy Mosca, Phd

Program Directors Retreat

Paper lab notebooks have been essentially unchanged for centuries, but as data gathering is increasingly digital and problems of reproducibility and retracted publications emerge, more researchers are switching to electronic lab notebooks (ELN), also known as electronic research notebooks (ERN). While it has lab in its name, LabArchives is flexible enough for many uses across research disciplines. LabArchives is an ERN produced by Elsevier and provided by Jefferson at no additional charge to all its staff, students and faculty.

Causality Analysis And Cell Network Modeling Of Spatial Calcium Signaling Patterns In Liver Lobules., Aalap Verma, Anil Noronha Antony, Babatunde A. Ogunnaike, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Dynamics as well as localization of Ca2+ transients plays a vital role in liver function under homeostatic conditions, repair, and disease. In response to circulating hormonal stimuli, hepatocytes exhibit intracellular Ca2+ responses that propagate through liver lobules in a wave-like fashion. Although intracellular processes that control cell autonomous Ca2+ spiking behavior have been studied extensively, the intra- and inter-cellular signaling factors that regulate lobular scale spatial patterns and wave-like propagation of Ca2+ remain to be determined. To address this need, we acquired images of cytosolic Ca2+ transients in 1300 hepatocytes situated across several mouse liver lobules over a period of …

Cellular Network Modeling And Single Cell Gene Expression Analysis Reveals Novel Hepatic Stellate Cell Phenotypes Controlling Liver Regeneration Dynamics, Daniel Cook, Sirisha Achanta, Jan B. Hoek, Babatunde A. Ogunnaike, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Background: Recent results from single cell gene and protein regulation studies are starting to uncover the previously underappreciated fact that individual cells within a population exhibit high variability in the expression of mRNA and proteins (i.e., molecular variability). By combining cellular network modeling, and high-throughput gene expression measurements in single cells, we seek to reconcile the high molecular variability in single cells with the relatively low variability in tissue-scale gene and protein expression and the highly coordinated functional responses of tissues to physiological challenges. In this study, we focus on relating the dynamic changes in distributions of hepatic stellate cell …

Control Of Ccnd1 Ubiquitylation By The Catalytic Saga Subunit Usp22 Is Essential For Cell Cycle Progression Through G1 In Cancer Cells., Victoria J. Gennaro, Timothy J. Stanek, Amy R. Peck, Yunguang Sun, Feng Wang, Shuo Qie, Karen E. Knudsen, Hallgeir Rui, Tauseef Butt, J. Alan Diehl, Steven B. Mcmahon

Department of Biochemistry and Molecular Biology Faculty Papers

Overexpression of the deubiquitylase ubiquitin-specific peptidase 22 (USP22) is a marker of aggressive cancer phenotypes like metastasis, therapy resistance, and poor survival. Functionally, this overexpression of USP22 actively contributes to tumorigenesis, as USP22 depletion blocks cancer cell cycle progression in vitro, and inhibits tumor progression in animal models of lung, breast, bladder, ovarian, and liver cancer, among others. Current models suggest that USP22 mediates these biological effects via its role in epigenetic regulation as a subunit of the Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional cofactor complex. Challenging the dogma, we report here a nontranscriptional role for USP22 via a direct effect on the …

Nurses Alumni Association Bulletin, Fall 2018, Susan Albrecht Curcio

Nursing Alumni Bulletins

2018 – 2019 Meeting Dates Calendar

2019 Annual Luncheon and Meeting Notice

Officers, Committee Chairs, and Satellite

2018 President’s Message

Treasurer’s Report

Resume of Minutes

Office News

Committee Reports

• Social
• Relief Trust Fund
• Satellite – Harrisburg Satellite Area
• Scholarship
• By-Laws
• Nominating
• Bulletin

Jefferson Office of Alumni Relations

Annual Giving

Janet C. Hindson Award

• Janet C. Hindson Award Winner

News About and From Our Graduates

Pearls of Wisdom

Brain Health by YOU...and by Music!

Three Months at Byberry

Happy Birthday – To Be 80 or More

Annual Luncheon

• 1969 50th Anniversary Class List for 2019 Annual Luncheon
• Luncheon Photos
• Annual Luncheon …

The Anti-Cancer Effect Of Retinoic Acid Signaling In Crc Occurs Via Decreased Growth Of Aldh+ Colon Cancer Stem Cells And Increased Differentiation Of Stem Cells, Shirin R. Modarai, Anindita Gupta, Lynn M. Opdenaker, Ryan Kowash, Gabriel Masters, Vignesh Viswanathan, Tao Zhang, Jeremy Z. Fields, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: Tumorigenesis is driven by stem cell (SC) overpopulation. BecauseALDH is both a marker for SCs in many tissues and a key enzyme in retinoid acid (RA)signaling, we studied RA signaling in normal and malignant colonic SCs.Hypothesis: RA signaling regulates growth and differentiation of ALDH+ colonicSCs dysregulation of RA signaling contributes to SC overpopulation and colorectalcancer (CRC) development.Methods: We analyzed normal and malignant colonic tissues and CRC cell linesto see if retinoid receptors (RXR &RAR) are exclusively expressed in ALDH+ SCs,and if RA signaling changes during CRC development. We determined whether RAsignaling regulates cancer SC (CSC) proliferation, differentiation, sphere formation,and …

Jefferson Digital Commons Quarterly Report: July-September 2018, Kelsey Duinkerken, Msi, James Copeland, Libt

Jefferson Digital Commons Reports

This quarterly report includes:

• New Collection Alert
• Articles
• Code Red: Battling the Plague of Gun Violence
• Dissertations
• From the Archives
• Grand Rounds and Lectures
• House Staff Quality Improvement and Patient Safety Posters
• Journals and Newsletters
• Nexus Maximus
• Posters
• Third Annual Sepsis Symposium
• What People are Saying

Using Concept Mapping To Develop A Human Rights Based Indicator Framework To Assess Country Efforts To Strengthen Rehabilitation Provision And Policy: The Rehabilitation System Diagnosis And Dialogue Framework (Resyst), Dimitrios Skempes, John L. Melvin, Per Von Groote, Gerold Stucki, Jerome Bickenbach

Department of Rehabilitation Medicine Faculty Papers

Background: Rehabilitation is crucial for the realization of the right to health and a proper concern of global health. Yet, reliable information to guide rehabilitation service planning is unavailable in many countries in part due to the lack of appropriate indicators. To ensure universal health coverage and meet the central imperative of "leaving no one behind" countries must be able to assess key aspects of rehabilitation policy and provision and monitor how they have discharged their human rights responsibilities towards those most disadvantaged, including people with disability. This article describes the process of developing an expert guided indicator framework to …

The Bulletin: Sidney Kimmel Medical College At Thomas Jefferson University, Volume 67, Issue 3, Fall 2018

The Bulletin (formerly the Jefferson Medical College Alumni Bulletin)

This issue includes:

• Explaining Uncertainty
• A Series of Fortunate Events
• 2018 Alumni Weekend
• The Dean's Column
• Findings
• The Jefferson Legacy
• Time Capsule
• On Campus
• Jefferson Researcher Explores Cell Death Controls and Effects
• New Alumni Association President
• Class Notes
• In Memoriam
• By the Numbers

Severe Lumbar Disability Is Associated With Decreased Psoas Cross-Sectional Area In Degenerative Spondylolisthesis, Scott C. Wagner, Arjun S. Sebastian, James C. Mckenzie, Joseph S. Butler, Ian D. Kaye, Patrick B. Morrissey, Alexander R. Vaccaro, Christopher K. Kepler

Rothman Institute Papers

Study Design: Retrospective cohort. Objectives: Alterations in lumbar paraspinal muscle cross-sectional area (CSA) may correlate with lumbar pathology. The purpose of this study was to compare paraspinal CSA in patients with degenerative spondylolisthesis and severe lumbar disability to those with mild or moderate lumbar disability, as determined by the Oswestry Disability Index (ODI). Methods: We retrospectively reviewed the medical records of 101 patients undergoing lumbar fusion for degenerative spondylolisthesis. Patients were divided into ODI score ≤40 (mild/moderate disability, MMD) and ODI score >40 (severe disability, SD) groups. The total CSA of the psoas and paraspinal muscles were measured on preoperative …

Designing The Ideal Perioperative Pain Management Plan Starts With Multimodal Analgesia., Eric S. Schwenk, Edward R. Mariano

Department of Anesthesiology Faculty Papers

Multimodal analgesia is defined as the use of more than one pharmacological class of analgesic medication targeting different receptors along the pain pathway with the goal of improving analgesia while reducing individual class-related side effects. Evidence today supports the routine use of multimodal analgesia in the perioperative period to eliminate the over-reliance on opioids for pain control and to reduce opioid-related adverse events. A multimodal analgesic protocol should be surgery-specific, functioning more like a checklist than a recipe, with options to tailor to the individual patient. Elements of this protocol may include opioids, non-opioid systemic analgesics like acetaminophen, non-steroidal anti-inflammatory …

Bath-Related Headache, Aliza Kumpinsky, Stephanie J. Nahas

Department of Neurology Faculty Papers

PURPOSE OF REVIEW: The purpose of this review is to summarize the most up-to-date literature on bath-related headache, a rare disorder.

RECENT FINDINGS: Initially described in middle-aged Asian women, it is now reported in a wider demographic. More information is available about the pathophysiology of bath-related headache, including its classification as a subtype of reversible cerebral vasoconstriction syndrome (RCVS). Nimodipine can be effective in patients both with and without vasospasm. Bath-related headache is a rare form of thunderclap headache. Although its mechanism is still unclear, it is associated with vasospasm and RCVS. Controlled trials investigating the use of nimodipine and …

Three Years Of Growth Hormone Therapy In Children Born Small For Gestational Age: Results From The Answer Program, Robert Rapaport, Peter Lee, Judith L. Ross, Paul Saenger, Vlady Ostrow, Giuseppe Piccoli

Department of Pediatrics Faculty Papers

Growth hormone (GH) is used to treat short stature and growth failure associated with growth disorders. Birth size and GH status variably modulate response to GH therapy. The aim of this study was to determine the effect of birth size on response to GH therapy, and to determine the impact of GH status in patients born small for gestational age (SGA) on response to GH therapy. Data from the prospective, non-interventional American Norditropin® Studies: Web-Enabled Research (ANSWER) Program were analyzed for several growth outcomes in response to GH therapy over 3 years. GH-naïve children from the ANSWER Program were included …

A Systematic Review Of Treating Recurrent Head And Neck Cancer: A Reintroduction Of Brachytherapy With Or Without Surgery., Julianna Rodin, Voichita Bar-Ad, David Cognetti, Joseph Curry, Jennifer Johnson, Chad Zender, Laura Doyle, David Kutler, Benjamin E. Leiby, William M. Keane, Adam J. Luginbuhl

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

Purpose: To review brachytherapy use in recurrent head and neck carcinoma (RHNC) with focus on its efficacy and complication rates.

Material and methods: A literature search of PubMed, Ovid, Google Scholar, and Scopus was conducted from 1990 to 2017. Publications describing treatment of RHNC with brachytherapy with or without surgery were included. The focus of this review is on oncologic outcomes and the safety of brachytherapy in the recurrent setting.

Results: Thirty studies involving RHNC treatment with brachytherapy were reviewed. Brachytherapy as adjunctive treatment to surgical resection appears to be associated with an improved local regional control and overall survival, …

Synthetic Dna Immunotherapy In Biochemically Relapsed Prostate Cancer, N. Shore, E. I. Heath, L. T. Nordquist, H. Cheng, K. Bhatt, M. Morrow, T. Mcmullan, K. Kraynyak, J. Lee, B. Sacchetta, L. Liu, S. Rosencranz, S. T. Tagawa, L. J. Appleman, R. Tutrone, J. Garcia, Y. Whang, W. Kelly, I. Csiki, M. L. Bagarazzi

Department of Medical Oncology Faculty Papers

Background: INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12), a synthetic DNA immunotherapy, was assessed for safety, immunogenicity and efficacy in biochemically recurrent prostate cancer patients (pts).

Methods: Phase I, open-label, multi-center study in the US included pts with rising PSA after surgery and/or RT, PSA doubling time (PSADT) >3 months (mos), testosterone >150 ng/dL and no concurrent ADT. Safety, immunogenicity and efficacy (PSA kinetics, PFS) were evaluated in 4 treatment arms of 15 pts each. Arms A: 2mg INO-5150, B: 8.5 mg INO-5150, C: 2mg INO-5150 + 1mg INO-9012 and D: 8.5mg INO-5150 + 1mg INO-9012. Pts received 4 IM …

Complications Associated With Volar Locking Plate Fixation Of Distal Radial Fractures., Todd H. Alter, Asif M. Ilyas

Rothman Institute Papers

• Volar locked plating is the most frequently utilized method for internal fixation of distal radial fractures.
• The overall complication rate for volar plating of distal radial fractures appears to be relatively low compared with other operative fixation methods.
• Carpal tunnel syndrome is the most commonly reported complication.
• However, this may occur after a distal radial fracture regardless of treatment method, with reported rates ranging from 0% to 20% with conservative management and 0% to 14% with volar plating.
• Extensor tendon rupture has been reported at rates of 0% to 4% and is the most frequent complication requiring plate removal.
• Variable-angle …

Stress Fractures Of The Elbow In The Throwing Athlete: A Systematic Review., Shelby R. Smith, Nirav K. Patel, Alex E. White, Christopher J Hadley, Christopher C. Dodson

Rothman Institute Papers

Background: Stress fractures of the elbow are rare in throwing athletes and present a challenge from both a management and rehabilitation perspective. Although the incidence of stress fractures of the elbow is increasing, there is a lack of data in the literature focused on throwers.

Purpose: To evaluate studies regarding the management and outcomes of stress fractures of the elbow in throwing athletes.

Study Design: Systematic review; Level of evidence, 4.

Methods: A systematic review was conducted by searching the Scopus, PubMed, and Cochrane Library electronic databases to identify studies reporting on the management and outcomes of stress fractures in …

Era Of Direct Acting Anti-Viral Agents For The Treatment Of Hepatitis C., Monjur Ahmed

Division of Gastroenterology and Hepatology Faculty Papers

Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have stepped into the era of direct acting anti-viral agents (DAAs) against hepatitis C virus. Treatment of hepatitis C is now extremely effective, tolerable and requires a short duration of intake of oral agents. Less monitoring is required with the current therapy and drug-drug interactions are less than the previous regimen. The current treatment options of chronic hepatitis C with various DAAs are discussed in this article.

Polymicrobial Sepsis Influences Nk-Cell-Mediated Immunity By Diminishing Nk-Cell-Intrinsic Receptor-Mediated Effector Responses To Viral Ligands Or Infections., Isaac J. Jensen, Christina S. Winborn, Micaela G. Fosdick, Peng Shao, Mikaela M. Tremblay, Qiang Shan, Sandeep Kumar Tripathy, Christopher M. Snyder, Hai-Hui Xue, Thomas S. Griffith, Jon C. Houtman, Vladimir P. Badovinac

Department of Microbiology and Immunology Faculty Papers

The sepsis-induced cytokine storm leads to severe lymphopenia and reduced effector capacity of remaining/surviving cells. This results in a prolonged state of immunoparalysis, that contributes to enhanced morbidity/mortality of sepsis survivors upon secondary infection. The impact of sepsis on several lymphoid subsets has been characterized, yet its impact on NK-cells remains underappreciated-despite their critical role in controlling infection(s). Here, we observed numerical loss of NK-cells in multiple tissues after cecal-ligation-and-puncture (CLP)-induced sepsis. To elucidate the sepsis-induced lesions in surviving NK-cells, transcriptional profiles were evaluated and indicated changes consistent with impaired effector functionality. A corresponding deficit in NK-cell capacity to produce …