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Surgical Intensivist And Global Critical Care: Is There A Role?, Jana B.A. Macleod, Orlando C. Kirton, Linda L. Maerz

Abington Jefferson Health Papers

No abstract provided.

Racemose Neurocysticercosis., Kristin Krupa, Kelly Krupa, Bs, Mary L Pisculli, Deena M Athas, Christopher J Farrell, Md

Department of Neurosurgery Faculty Papers

BACKGROUND: Neurocysticercosis (NCC) is an invasive parasitic infection of the central nervous system caused by the larval stage of the tapeworm Taenia solium. The clinical manifestations of NCC depend on the parasitic load and location of infection, as well as the developmental stage of the cysticerci and host immune response, with symptoms ranging from subclinical headaches to seizures, cerebrovascular events, and life-threatening hydrocephalus. Racemose NCC represents a particularly severe variant of extraparenchymal NCC characterized by the presence of multiple confluent cysts within the subarachnoid space and is associated with increased morbidity and mortality, as well as a decreased response to …

Dysregulation Of The Haem-Haemopexin Axis Is Associated With Severe Malaria In A Case-Control Study Of Ugandan Children., Robyn E Elphinstone, Frank Riley, Tian Lin, Sarah Higgins, Aggrey Dhabangi, Charles Musoke, Christine Cserti-Gazdewich, Raymond F. Regan, H Shaw Warren, Kevin C Kain

Department of Medicine Faculty Papers

BACKGROUND: Malaria is associated with haemolysis and the release of plasma haem. Plasma haem can cause endothelial injury and organ dysfunction, and is normally scavenged by haemopexin to limit toxicity. It was hypothesized that dysregulation of the haem-haemopexin pathway contributes to severe and fatal malaria infections.

METHODS: Plasma levels of haemin (oxidized haem), haemopexin, haptoglobin, and haemoglobin were quantified in a case-control study of Ugandan children with Plasmodium falciparum malaria. Levels at presentation were compared in children with uncomplicated malaria (UM; n = 29), severe malarial anaemia (SMA; n = 27) or cerebral malaria (CM; n = 31), and evaluated …

Antibiotic Resistance And The White House Forum On Antibiotic Stewardship, Mary Lou Manning Phd, Crnp, Cic, Faan

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Clinical Experience At Pasteur Clinic Đà Lạt, Vietnam, Emma Howard-Young, Jordan Howard-Young, Ma

CwiC Posters

History of the Pasteur Clinic Đà Lạt

The Pasteur Clinic is associated with the Institut Pasteur, part of the international network of research institutes dedicated to the prevention and treatment of infectious diseases. The Đà Lạt branch of Vietnam’s Institut Pasteur was built between 1930 and 1936 under the direction of Dr. Alexandre Yersin, a physician remembered for identifying Yersinia pestis as the causative agent of Plague and a student of the eponymous French chemist and microbiologist Louis Pasteur. While many overt references to the French colonial tradition have been supplanted in Vietnam by nationalist sentiments, the Institut Pasteur …

Mitochondrial Mass, A New Metabolic Biomarker For Stem-Like Cancer Cells: Understanding Wnt/Fgf-Driven Anabolic Signaling., Rebecca Lamb, Gloria Bonuccelli, Béla Ozsvári, Maria Peiris-Pagès, Marco Fiorillo, Duncan L Smith, Generoso Bevilacqua, Chiara Maria Mazzanti, Liam A Mcdonnell, Antonio Giuseppe Naccarato, Maybo Chiu, Luke Wynne, Ubaldo E Martinez-Outschoorn, Federica Sotgia, Michael P. Lisanti

Kimmel Cancer Center Faculty Papers

Here, we developed an isogenic cell model of "stemness" to facilitate protein biomarker discovery in breast cancer. For this purpose, we used knowledge gained previously from the study of the mouse mammary tumor virus (MMTV). MMTV initiates mammary tumorigenesis in mice by promoter insertion adjacent to two main integration sites, namely Int-1 (Wnt1) and Int-2 (Fgf3), which ultimately activates Wnt/β-catenin signaling, driving the propagation of mammary cancer stem cells (CSCs). Thus, to develop a humanized model of MMTV signaling, we over-expressed WNT1 and FGF3 in MCF7 cells, an ER(+) human breast cancer cell line. We then validated that MCF7 cells …

Diagnostic Options And Challenges For Dengue And Chikungunya Viruses., Stacey K. Mardekian, Amity L. Roberts, Phd, D(Abmm)

Department of Medical Genetics Faculty Papers

Dengue virus (DENV) and Chikungunya virus (CHIKV) are arboviruses that share the same Aedes mosquito vectors and thus overlap in their endemic areas. These two viruses also cause similar clinical presentations, especially in the initial stages of infection, with neither virus possessing any specific distinguishing clinical features. Because the outcomes and management strategies for these two viruses are vastly different, early and accurate diagnosis is imperative. Diagnosis is also important for surveillance, outbreak control, and research related to vaccine and drug development. Available diagnostic tests are aimed at detection of the virus, its antigenic components, or the host immune antibody …

Human Polyclonal Antibodies Produced Through Dna Vaccination Of Transchromosomal Cattle Provide Mice With Post-Exposure Protection Against Lethal Zaire And Sudan Ebolaviruses., Callie E Bounds, Steven A Kwilas, Ana I Kuehne, Jennifer M Brannan, Russell R Bakken, John M Dye, Jay W Hooper, Lesley C Dupuy, Barry Ellefsen, Drew Hannaman, Hua Wu, Jin-An Jiao, Eddie J Sullivan, Connie S Schmaljohn, Matthias J. Schnell

Department of Medicine Faculty Papers

DNA vaccination of transchromosomal bovines (TcBs) with DNA vaccines expressing the codon-optimized (co) glycoprotein (GP) genes of Ebola virus (EBOV) and Sudan virus (SUDV) produce fully human polyclonal antibodies (pAbs) that recognize both viruses and demonstrate robust neutralizing activity. Each TcB was vaccinated by intramuscular electroporation (IM-EP) a total of four times and at each administration received 10 mg of the EBOV-GPco DNA vaccine and 10 mg of the SUDV-GPco DNA vaccine at two sites on the left and right sides, respectively. After two vaccinations, robust antibody responses (titers > 1000) were detected by ELISA against whole irradiated EBOV or SUDV …

Dissecting Tumor Metabolic Heterogeneity: Telomerase And Large Cell Size Metabolically Define A Sub-Population Of Stem-Like, Mitochondrial-Rich, Cancer Cells., Rebecca Lamb, Bela Ozsvari, Gloria Bonuccelli, Duncan L Smith, Richard Pestell, Ubaldo E. Martinez-Outshoorn, Md, Robert B Clarke, Federica Sotgia, Michael P Lisanti

Kimmel Cancer Center Faculty Papers

Tumor cell metabolic heterogeneity is thought to contribute to tumor recurrence, distant metastasis and chemo-resistance in cancer patients, driving poor clinical outcome. To better understand tumor metabolic heterogeneity, here we used the MCF7 breast cancer line as a model system to metabolically fractionate a cancer cell population. First, MCF7 cells were stably transfected with an hTERT-promoter construct driving GFP expression, as a surrogate marker of telomerase transcriptional activity. To enrich for immortal stem-like cancer cells, MCF7 cells expressing the highest levels of GFP (top 5%) were then isolated by FACS analysis. Notably, hTERT-GFP(+) MCF7 cells were significantly more efficient at …

Relationships Between Cancer Pattern, Country Income And Geographical Region In Asia., Chirk Jenn Ng, Chin Hai Teo, Nurdiana Abdullah, Wei Phin Tan, Hui Meng Tan

Department of Surgery Faculty Papers

BACKGROUND: Cancer incidence and mortality varies across region, sex and country's economic status. While most studies focused on global trends, this study aimed to describe and analyse cancer incidence and mortality in Asia, focusing on cancer site, sex, region and income status.

METHODS: Age-standardised incidence and mortality rates of cancer were extracted from the GLOBOCAN 2012 database. Cancer mortality to incidence ratios (MIRs) were calculated to represent cancer survival. The data were analysed based on the four regions in Asia and income.

RESULTS: Cancer incidence rate is lower in Asia compared to the West but for MIR, it is the …

The Role Of Perlecan And Endorepellin In The Control Of Tumor Angiogenesis And Endothelial Cell Autophagy., Stephen Douglass, Atul Goyal, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

During tumor growth and angiogenesis there is a dynamic remodeling of tissue architecture often accompanied by the release of extracellular matrix constituents full of biological activity. One of the key constituents of the tumor microenvironment is the large heparan sulfate proteoglycan perlecan. This proteoglycan, strategically located at cell surfaces and within basement membranes, is a well-defined pro-angiogenic molecule when intact. However, when partially processed by proteases released during cancer remodeling and invasion, the C-terminal fragment of perlecan, known as endorepellin, has opposite effects than its parent molecule. Endorepellin is a potent inhibitor of angiogenesis by exerting a dual receptor antagonism …

Differential Host Immune Responses After Infection With Wild-Type Or Lab-Attenuated Rabies Viruses In Dogs., Clement W Gnanadurai, Yang Yang, Ying Huang, Zhenguang Li, Christina M Leyson, Tanya L Cooper, Simon R Platt, Stephen B Harvey, D Craig Hooper, Milosz Faber, Zhen F Fu

Department of Medical Genetics Faculty Papers

METHODOLOGY/PRINCIPAL FINDINGS: The experimental infection of dogs with TriGAS induced high levels of VNA in the serum, whereas wt RABV infection did not. Dogs infected with TriGAS developed antibodies against the virus including its glycoprotein, whereas dogs infected with DRV-NG11 only developed rabies antibodies that are presumably specific for the nucleoprotein, (N) and not the glycoprotein (G). We show that infection with TriGAS induces early activation of B cells in the draining lymph nodes and persistent activation of DCs and B cells in the blood. On the other hand, infection with DRV-NG11 fails to induce the activation of DCs and …

Download Entire Issue Of The Medicine Forum, Volume 15, 2013-2014

The Medicine Forum

Download entire issue of The Medicine Forum, Volume 15, 2013-2014

Tb, Or Not Tb?, Michael A. Valentino, Md, Phd

The Medicine Forum

The patient is a 43-year-old African American male with a past medical history of hypertension, hyperlipidemia, and chronic low back pain who presented to the ER for worsening dyspnea and a 30-lb weight loss over the past 3 months. He also reported a nonproductive cough over this period of time as well as an eruption of small ~1cm flesh-colored nodules on his extremities and trunk. He denied any fevers, chills, or night sweats. In the ER, he had a chest x-ray performed (Figure 1) which showed diffuse centrilobular nodules visualized throughout the lung fields in a miliary pattern. He subsequently …

A Case Of Fanconi’S Syndrome In A Patient With Hiv, Mariam Kabir, Md, Phd, Christopher Miller, Md, Rakesh Gulati, Md, Mrcp, William R. Short, Md, Mph

The Medicine Forum

Introduction

Tenofovir disoproxil fumarate (TDF) is a nucleotide analogue reverse transcriptase inhibitor (NtRTI), which blocks reverse transcriptase, an enzyme found in HIV. Since its approval for use in HIV by the FDA in 2001, it has contributed to effective treatment in numerous patients. The most common side effects include nausea, vomiting, diarrhea, asthenia, abdominal pain and hepatotoxicity. A less common side effect is nephrotoxicity leading to Fanconi’s syndrome. Here is an interesting case of Fanconi’s Syndrome caused by Tenofovir.

Case

A 50-year-old Caucasian female with a past medical history of HIV and Hepatitis C presented to the Emergency Department with …

A Case Of Septic Portal Vein Thrombosis (Pylephlebitis), Erin Carnish, Md, Andrew Garrett, Md, Mary Slome, Ms1

The Medicine Forum

INTRODUCTION

Pylephlebitis, defined as suppurative thrombosis of the portal vein often associated with bacteremia, is a rare and serious complication of intra-abdominal infections. Prior to antibiotics, the mortality rate of this disease approached 100%.1 The veins adjacent to the infection are the first to be involved, with later spread to the portal vein and possibly the mesenteric and splenic veins.2-3 Extension into the mesenteric veins can lead to bowel necrosis and increased morbidity and mortality.2-4

CASE PRESENTATION

A 63-year old male with a history of hypertension presented to the emergency department with one week of progressively worsening malaise, chills, severe …

A Case Of Complete Heart Block Secondary To Anca-Associated Vasculitis, Krista Lim-Hing, Md

The Medicine Forum

INTRODUCTION

Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitides are systemic autoimmune diseases that often present as non-specific prodromal symptoms such as fever, fatigue, headache, and weight loss.1 With modern treatment, the disease has changed from being universally fatal to being treatable. It can have a chronic relapsing and remitting course. Therefore, early diagnosis is necessary.2,3

CASE PRESENTATION

A 53-year-old male with a past medical history of chronic sinusitis and some epistaxis needing multiple courses of antibiotics and steroids, was admitted after being diagnosed with high-grade heart block at another institution. He was found to have a heart rate of 26 and …

An Unusual Atrial Mass: A Case Study, David F. Reilly, Bs, Christina Lindenmeyer, Md

The Medicine Forum

BACKGROUND

This case highlights the evolution of a broad differential diagnosis when presented with a rare and diagnostically enigmatic clinical finding.

Hiv Screening: A Review Of Nationally Recommended Guidelines And Specific Instances In Which Hiv Screening Is Often Overlooked, Anusha Ganesh, Md

The Medicine Forum

INTRODUCTION

According to the Centers for Disease Control and Prevention (CDC), one in five human immunodeficiency virus (HIV)-infected individuals are currently living without knowledge of their diagnosis.1 In 2006, the cost of a rapid HIV test with pre/post-test HIV counseling was anywhere between 48-64 US dollars (USD). The majority of the cost incurred was for HIV counseling, with the cost of the rapid HIV test being between 8-25 USD.2 Research looking at the cost-effectiveness of HIV screening shows that it is more cost-effective than routine screening for breast cancer with mammography yearly or even routine screening for diabetes mellitus with …

A Case Of Fibrosing Mediastinitis, Esther Molnar, Md

The Medicine Forum

Introduction

Fibrosing mediastinitis (FM) is a rare disease of slowly progressive fibrosis that encases major mediastinal structures. Complications include obstruction of mediastinal vasculature, including main pulmonary arteries, which may lead to life-threatening hemodynamic compromise. In North America, the disease is usually a sequela of histoplasmosis. Because Histoplasma capsulatum (H. capsulatum) is found in the Ohio River Valley, physicians in Pennsylvania must be able to recognize and diagnose the disease.

Case Presentation

The patient is a 59 year-old female who was seen for follow-up in April 2013. She originally presented to the outpatient office in 2008 with chronic chest pain and …

A Speedy Recovery With Medical Management In A Patient With Emphysematous Gastritis, Tanvi Khurana, Md

The Medicine Forum

INTRODUCTION

Emphysematous gastritis is a rare and serious condition characterized by evidence of intramural air and inflammation of the gastric wall as well as systemic toxicity. It is generally caused by local infection by gas-forming organisms through a mucosal defect or via hematogenous spread from a distant focus.1 Since emphysematous gastritis has a fulminant course with a mortality rate of 60%, prompt recognition as well as early treatment are crucial.2 Here, we present a case of a 65 year-old male who presented with abdominal pain and had CT findings consistent with emphysematous gastritis. He was treated with antibiotics and had …

Recurrent Cryptococcosis In A Human Immunodeficiency Virus-Negative Patient, Lillian C. Man, Md

The Medicine Forum

Introduction

Idiopathic CD4+ lymphocytopenia (ICL) is a rare disorder that can predispose otherwise immunocompetent individuals to life-threatening opportunistic infections. We present a case of a human immunodeficiency virus (HIV)-negative patient with ICL who presented with recurrent cryptococcosis.

Case Presentation

A 39-year-old Caucasian, HIV-negative male with a past medical history of stroke 13 years prior to admission and an episode of cryptococcal meningitis 18 months prior to admission presented to the hospital with generalized weakness for 7 days. The patient had a 10 pack-year smoking history and no significant environmental or occupational exposures. On admission, vital signs were significant for a …

Sustained Achromobacter Xylosoxidans Bacteremia In A Patient With Adenocarcinoma Of The Colon, Matt Enriquez, Ms4, Andi Favini, Ms4, Kevin Curl, Md

The Medicine Forum

Introduction

Achromobacter xylosoxidans is a rare cause of bacteremia; however patients with underlying illness, especially malignancies, are at increased risk of infection. Antibiotic therapy against this pathogen can be difficult owing to its inherent resistance to multiple common antibiotics.

Case Presentation

A 69-year-old male with adenocarcinoma of the colon status post right hemicolectomy and chemotherapy presented with fever and fatigue 10 days following endoscopic retrograde cholangiopancreatography (ERCP) with biliary stent placement for new liver metastases. The patient had undergone partial hemicolectomy and had completed 12 cycles of adjuvant FOLFOX (leucovorin, 5-fluorouracil, and oxaliplatin) at the time of initial diagnosis. Two …

Sudden Vision Loss During Hemodialysis, Andrew W. Panakos, Md

The Medicine Forum

Introduction

Catheter-related blood stream infections (CRBSIs) are a common and unfortunate consequence of prolonged vascular access in hemodialysis patients. Metastatic infections are feared sequelae of bacteremia, and include endocarditis, osteomyelitis, septic arthritis, epidural abscess, and endophthalmitis.1 The following is a case of Serratia endophthalmitis originating from a tunneled-dialysis catheter.

Case Presentation

A 47 year-old Caucasian female with a history of end stage renal disease on hemodialysis, Type 2 diabetes mellitus, and hypertension was undergoing her routinely scheduled hemodialysis session when she experienced “flashes of hot pink” in her left eye. The hemodialysis session was terminated, and the patient returned home. …

Pulmonary Mucormycosis In A Patient With Acute Myeloid Leukemia, Jonathan Pan, Md, Margaret Kasner, Md, Sheel Patel, Md, Gretchen Diemer, Md

The Medicine Forum

Introduction

Mucormycosis is a rare fungal infection that is common amongst uncontrolled diabetics and immunocompromised patients. The most common clinical presentation is rhino-orbital-cerebral infection, which typically affects diabetics with ketoacidosis.1 Less commonly, pulmonary mucormycosis can occur in patients with hematologic malignancy, solid organ transplant and patients taking steroids or deferoxamine.1 The following report describes a 25-year-old male with Acute Myeloid Leukemia (AML) who developed a pulmonary mucormycosis infection. With a mortality rate of about 87%, this case represents a favorable outcome for a rare and often lethal diagnosis.

Case Description

A 25-year-old male with no past medical history presented to …

Acute Respiratory Distress Syndrome From Tick-Borne Human Granulocytic Anaplasmosis Infection, Vedang Patel, Md

The Medicine Forum

Introduction

Tick-borne infections were first formally recognized over a century ago, but it was only in 1990 that the first case of human granulocytic anaplasmosis (HGA), a tick-borne infection caused by Anaplasma phagocytophilum, was identified.1,2 Like other tick-borne infections, HGA presents as a nonspecific febrile illness. The most common clinical features are fever, headache, myalgia and malaise.2 This case report presents a rare but serious complication of HGA – acute respiratory distress syndrome (ARDS).

CASE PRESENTATION

A 49-year-old female with no past medical history presented to her local emergency department with complaints of fevers, headache, neck pain, myalgia, and malaise. …

Role Of Phenol-Soluble Modulins In Formation Of Staphylococcus Aureus Biofilms In Synovial Fluid., Sana S Dastgheyb, Amer E Villaruz, Katherine Y Le, Vee Y Tan, Anthony C Duong, Som S Chatterjee, Gordon Y C Cheung, Hwang-Soo Joo, Noreen J Hickok, Michael Otto

Department of Orthopaedic Surgery Faculty Papers

Staphylococcus aureus is a leading cause of prosthetic joint infections, which, as we recently showed, proceed with the involvement of biofilm-like clusters that cause recalcitrance to antibiotic treatment. Here we analyzed why these clusters grow extraordinarily large, reaching macroscopically visible extensions (>1 mm). We found that while specific S. aureus surface proteins are a prerequisite for agglomeration in synovial fluid, low activity of the Agr regulatory system and subsequent low production of the phenol-soluble modulin (PSM) surfactant peptides cause agglomerates to grow to exceptional dimensions. Our results indicate that PSMs function by disrupting interactions of biofilm matrix molecules, such …

Caspase-8 Scaffolding Function And Mlkl Regulate Nlrp3 Inflammasome Activation Downstream Of Tlr3., Seokwon Kang, Teresa Fernandes-Alnemri, Corey Rogers, Lindsey Mayes, Ying Wang, Christopher Dillon, Linda Roback, William Kaiser, Andrew Oberst, Junji Sagara, Katherine A Fitzgerald, Douglas R Green, Jianke Zhang, Edward S Mocarski, Emad S Alnemri

Department of Biochemistry and Molecular Biology Faculty Papers

TLR2 promotes NLRP3 inflammasome activation via an early MyD88-IRAK1-dependent pathway that provides a priming signal (signal 1) necessary for activation of the inflammasome by a second potassium-depleting signal (signal 2). Here we show that TLR3 binding to dsRNA promotes post-translational inflammasome activation through intermediate and late TRIF/RIPK1/FADD-dependent pathways. Both pathways require the scaffolding but not the catalytic function of caspase-8 or RIPK1. Only the late pathway requires kinase competent RIPK3 and MLKL function. Mechanistically, FADD/caspase-8 scaffolding function provides a post-translational signal 1 in the intermediate pathway, whereas in the late pathway it helps the oligomerization of RIPK3, which together with …

Sepsis 2015: You Say You Wanted A Revolution, R. Phillip Dellinger, Md, Mccm

Division of Pulmonary, Allergy, and Critical Care Medicine Presentations and Grand Rounds

Objectives:

1. Understand current considerations for changing definitions of sepsis
2. Understand what we should do in the early management of sepsis
3. Understand the questions still to be answered in guiding early management of sepsis
4. Know what’s going on in clinical trials in sepsis

Overall Goals and Objectives:

Following this activity, a participant should be able to:

1. Recognize recent advances and developments in Pulmonary Medicine & Critical Care and translate into clinical practice

2. Integrate perspectives of multiple disciplines into decision-making on behalf of patients through structured plans for patient care.

3. Develop areas for future research and discuss appropriate …

Doxycycline Down-Regulates Dna-Pk And Radiosensitizes Tumor Initiating Cells: Implications For More Effective Radiation Therapy., Rebecca Lamb, Marco Fiorillo, Amy Chadwick, Bela Ozsvari, Kimberly J Reeves, Duncan L Smith, Robert B Clarke, Sacha J Howell, Anna Rita Cappello, Ubaldo E. Martinez-Outshoorn, Md, Maria Peiris-Pagès, Federica Sotgia, Michael P Lisanti

Kimmel Cancer Center Faculty Papers

DNA-PK is an enzyme that is required for proper DNA-repair and is thought to confer radio-resistance in cancer cells. As a consequence, it is a high-profile validated target for new pharmaceutical development. However, no FDA-approved DNA-PK inhibitors have emerged, despite many years of drug discovery and lead optimization. This is largely because existing DNA-PK inhibitors suffer from poor pharmacokinetics. They are not well absorbed and/or are unstable, with a short plasma half-life. Here, we identified the first FDA-approved DNA-PK inhibitor by "chemical proteomics". In an effort to understand how doxycycline targets cancer stem-like cells (CSCs), we serendipitously discovered that doxycycline …